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A new look at pericardial substitutes
Abstract
The presence of pericardial adhesions may increase morbidity and mortality during reoperation for cardiac disease. Pericardial substitutes (patches) are commercially available, and reportedly they reduce or prevent adhesions. We implanted five (1984 to 1985) newer pericardial substitutes in dogs. A new polytetrafluoroethylene surgical membrane, two types of glutaraldehyde-stabilized bovine pericardium, formaldehyde-preserved bovine pericardium, and glutaraldehyde-stabilized equine pericardial patches were each implanted in six adult dogs (total 30 dogs) with two dogs from each of the five groups killed at 3, 9, and 18 months. At autopsy the condition of each patch was recorded photographically, and specimens were substituted for histologic examination. Adhesions and epicardial reactions were graded as none, minimal, moderate, or severe. None of the materials produced severe pericardial adhesions, and no adhesions were detected in nine dogs. Eleven dogs had no epicardial reaction and only one showed a severe reaction. Adhesions to portions of the suture line required sharp dissection in 11 dogs. If there is concern over the possibility of calcification in heterologous tissue, polytetrafluoroethylene may be chosen. Patch type did not significantly alter patch behavior.
... Few studies have included exposure of the animals to cardiopulmonary bypass (CPB). Most of the tested materials have given good results in the animal studies(Heydom et al, 1987;Rhodes et al, 1989), but the long term clinical outcome, has been disappointing(Eng et al, 1989;Gallo et al, 1985). ...
... Gallo, Artinano et al., 1985;Heydom, Daniel et al., 1987). Some of the synthetic materials studied include Dacron polyester, silicone mbber, sihcone coated polyester fabrics, polytetrafluoroethylene (FI FE), and silicone filled PTFE(Laks et al, 1981;Reder et al, 1983). ...
... They concluded that Bovine pericardium appears to increase the difficulty of repeat stemotomy and recommended against its continued use. These clinical findings showed a marked difference to the animal studies(Gallo et al, 1978;Heydom, Daniel et al., 1987;Mathisen et al, 1986) that suggested that, at least in the short-term, bovine pericardium prevented severe adhesion. ...
The presence of pericardial adhesions prolongs the operation time and increases the risk of serious damage to the heart and other major vascular structures during resternotomy. The reported incidence of such damage is 2-6[percent]. Pericardial mesothelial cells have regenerative potential and exhibit fibrinolytic activity. The pericardial mesothelium therefore has the capacity to recover following cell loss or damage and has an actual or potential role in the break down of the fibrinous adhesions that serve as the initial scaffolding for the firm collagenous adhesions seen at reoperative surgery. These features of the pericardium may have been underestimated in much of the previous research into pericardial substitution. The studies in this thesis have demonstrated That during cardiac surgery there is a significant reduction in the pericardial fibrinolytic activity in comparison to initial activity. The recovery in fibrinolytic activity that occurs towards the end of the surgical procedure and afterwards never reaches the preoperative magnitude. That during cardiac surgery, simultaneous with the changes in the fibrinolytic activity, increasing pericardial inflammation occurs with a concomitant increase in mesothelial damage. Permanent residual damage is apparent in the reoperative pericardium. That during the reduction in pericardial fibrinolytic activity the simultaneous plasma tPA activity rises to a peak suggesting that the fall in pericardial fibrinolytic activity independent of the plasma tPA and haemodilution. That the cellular content of pericardial fluid is mainly mesothelial which may therefore contribute to mesothelial regeneration and recovery. The pericardial fluid, by virtue of its enzyme content, has the potential to take part in fibrinolytic activity. That the polyhydroxybutyrate pericardial patch does not confer any obvious short-term reoperative advantage in calves exposed to CPB surgery.
... Few studies have included exposure of the animals to cardiopulmonary bypass (CPB). Most of the tested materials have given good results in the animal studies(Heydom et al, 1987;Rhodes et al, 1989), but the long term clinical outcome, has been disappointing(Eng et al, 1989;Gallo et al, 1985). ...
... Gallo, Artinano et al., 1985;Heydom, Daniel et al., 1987). Some of the synthetic materials studied include Dacron polyester, silicone mbber, sihcone coated polyester fabrics, polytetrafluoroethylene (FI FE), and silicone filled PTFE(Laks et al, 1981;Reder et al, 1983). ...
... They concluded that Bovine pericardium appears to increase the difficulty of repeat stemotomy and recommended against its continued use. These clinical findings showed a marked difference to the animal studies(Gallo et al, 1978;Heydom, Daniel et al., 1987;Mathisen et al, 1986) that suggested that, at least in the short-term, bovine pericardium prevented severe adhesion. ...
The presence of pericardial adhesions prolongs the operation time and increases the risk of serious damage to the heart and other major vascular structures during resternotomy. The reported incidence of such damage is 2-6[percent]. Pericardial mesothelial cells have regenerative potential and exhibit fibrinolytic activity. The pericardial mesothelium therefore has the capacity to recover following cell loss or damage and has an actual or potential role in the break down of the fibrinous adhesions that serve as the initial scaffolding for the firm collagenous adhesions seen at reoperative surgery. These features of the pericardium may have been underestimated in much of the previous research into pericardial substitution. The studies in this thesis have demonstrated That during cardiac surgery there is a significant reduction in the pericardial fibrinolytic activity in comparison to initial activity. The recovery in fibrinolytic activity that occurs towards the end of the surgical procedure and afterwards never reaches the preoperative magnitude. That during cardiac surgery, simultaneous with the changes in the fibrinolytic activity, increasing pericardial inflammation occurs with a concomitant increase in mesothelial damage. Permanent residual damage is apparent in the reoperative pericardium. That during the reduction in pericardial fibrinolytic activity the simultaneous plasma tPA activity rises to a peak suggesting that the fall in pericardial fibrinolytic activity independent of the plasma tPA and haemodilution. That the cellular content of pericardial fluid is mainly mesothelial which may therefore contribute to mesothelial regeneration and recovery. The pericardial fluid, by virtue of its enzyme content, has the potential to take part in fibrinolytic activity. That the polyhydroxybutyrate pericardial patch does not confer any obvious short-term reoperative advantage in calves exposed to CPB surgery.
... Owing to a variety of reasons so far, the autologous pericardium could not be applied in some patients, and a safer resternotomy was realized with pericardial membrane substitute during the reoperation procedure. To reduce the pericardial adhesion during and after cardiac surgery, several attempts have been made by applying various kinds of substitutes for the pericardium, including expanded polytetrafluoroethylene (ePTFE) patches [4,5], glutaraldehyde-treated bovine or porcine pericardial xenografts [6,7] and silicone rubber [8]. Most recently, the research focus has turned to developing bioabsorbable antiadhesion barriers [9][10][11]. ...
... Macroscopic inspection was used to evaluate adhesion formation, the degree of which varied from 0 to 3 quantitatively, according to the adhesion rating scale reported by Heydorn et al. [6], where it was classified as grade 0 when there was no adhesion and grade 1 when adhesions could be easily dissected with a finger. When adhesions were of moderate strength, they were grade 2, while adhesions requiring sharp dissection were classified as grade 3. ...
... Various types of materials have been used so far to prevent detrimental adhesions; the materials used to reduce pericardial adhesions are classified into two categories, namely, bioabsorbable and non-bioabsorbable materials. Non-biodegradable materials, such as PTFE [18], silicone rubber [8] and xenograft pericardium [6], have been used to prevent formation of postoperative adhesions. However, it still remains limited for non-biodegradable materials due to their permanent nature, the use of chemical fixatives and formation of a fibrous capsule. ...
OBJECTIVES In paediatric cardiac surgery, reoperations remain challenging since the injury and the formation of dense adhesions before
reoperations can be life-threatening to the heart, bypass conduits or great vessels. To prevent the formation of dense adhesions,
a variety of different types of pericardial membrane substitute have been employed. However, due to peel formation, calcification
and infection, the routine application of these pericardial membrane substitute has not been achieved clinically. A novel
bioabsorbable membrane has been developed from polylactic acid (PLA) to overcome these drawbacks. The purpose of this study
was to assess the biosafety and the effectiveness of PLA membrane as a new bioabsorbable pericardial membrane substitute after
pericardium replacement in a rabbit model.
... Indeed, cardiac tamponade occurs more often after pericardial closure [5]. Many investigators have described materials that reduce adhesion formation in the retrosternal space [9,[11][12][13][14][15][16][17][18][19][20]. ...
... Previous studies have evaluated the ability of a variety of agents to reduce or prevent adhesion formation after cardiac operation. Sheep [14,18,22,23] and rabbit models [19] have also been used, but the canine model is used in the majority of the studies [9,[11][12][13][14][15][16][17]20]. Studies conducted using a canine model described adhesions between the epicardium and the pericardium. ...
... This technique also kept the lungs separated from each other anteriorly, making it a more analogous situation to human chest anatomy. Previous studies have reported the results of attempts to prevent adhesions using nonresorbable materials, such as polytetrafluoroethylene (PTFE) membrane [11][12][13][14], bovine pericardium, or equine pericardium [15][16][17][18]. These pericardial substitutes were evaluated by assessing adhesion formation between the epicardium and the substitute. ...
The formation of postoperative cardiac adhesions makes a repeat sternotomy time consuming and dangerous. Many attempts have been made to solve this problem by using either drugs to inhibit fibrinolytic activity or different types of pericardial substitutes. The results have not been satisfactory.
The efficacy of bioresorbable film prototypes made of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesions after cardiac operations in canine models was tested. After desiccation and abrasion of the epicardium, a transparent bioresorbable film was placed over the heart. The pericardium was closed to allow intrapericardial adhesions (n = 32) or left open and attached to the chest wall to induce retrosternal adhesions (n = 17). Postoperative recovery was similar among the groups. Retrosternal and pericardial adhesions were evaluated at necropsy 3 weeks later by assessing area, tenacity, and density of the adhesions.
In the control dogs, tenacious, dense adhesions were observed. In contrast, adhesion formation was reduced at all sites covered by the films. The bioresorbable films were efficacious in the reduction of adhesion formation between epicardium and pericardium or between epicardium and sternum after cardiac operation. The EO/LA 1.5 film most effectively prevented the early adhesions.
The bioresorbable films (EO/LA = 1.5, 2.5, and 3.0) significantly reduced adhesion formation, with EO/LA = 1.5 (Repel CV) being optimal. As the barrier was rapidly resorbed, the capsule formation induced by permanent barriers was avoided.
... Esses são os motivos pelos quais tem-se buscado maneiras de se fechar a cavidade pericárdica com técnicas diversas de pericardioplastia (10)(11)(12) e com substitutos do pericárdio, biológicos e sintéticos. Os primeiros podem ser autólogos (7,13,14) ou heterólogos (15)(16)(17)(18)(19)(20)(21) , os últimos, inabsorvíveis (22)(23)(24)(25)(26)(27) e absorvíveis (27)(28)(29)(30) . ...
... Nesses trabalhos, não há referências a reoperações. Com relação aos inabsorvíveis, a membrana cirúrgica de politetrafluoretileno (PTFE) é a que tem apresentado comportamento mais satisfatório (20,26,27,32) . Contudo, MEUS et al. (25) observaram, no cão, que a membrana de PTFE provoca intensa reação epicárdica que impede o reconhecimento dos vasos coronários subjacentes. ...
FUNDAMENTO: São numerosas as vantagens de se fechar a cavidade pericárdica após as operações cardíacas e pneumonectomias intrapericárdicas. OBJETIVO: Estudar o comportamento da membrana de látex natural como substituto parcial do pericárdio. MATERIAL E MÉTODOS: Em 16 cães, divididos em 3 grupos, ressecou-se um retalho elíptico da porção ântero-lateral esquerda do pericárdio (7 cm x 5 cm): Grupo A (n=4) - o retalho removido foi reimplantado imediatamente; Grupo B (n=8) - o retalho foi substituído por outro, de látex natural, com área equivalente e espessura de 0,3 mm; Grupo C (n=4) - retalho de látex de 0,7 mm de espessura. Em todos os animais, fixou-se o retalho com sutura contínua de fio de polipropileno 5-0 ou 6-0. No último grupo, foram dados 4 pontos adicionais, em U, ancorados em barras de dacron. Realizaram-se eletrocardiogramas (ECG) e leucogramas no pré e no pós-operatório, bem como estudo macro e microscópio post-mortem. RESULTADOS: Grupo A - auto-enxerto íntegro, macro e microscopicamente, fortemente aderido ao pulmão e frouxamente aderido ao epicárdio; Grupo B - deiscência parcial da sutura em 1 e total em 2 animais. A membrana de látex não aderiu nem ao pulmão nem ao epicárdio. Em 3 (37,5%) animais houve regeneração total e distinta do pericárdio subjacente ao látex, microscopicamente idêntico ao pericárdio nativo. Grupo C - suturas íntegras. Em 3 (75%) animais observou-se regeneração pericárdica total e distinta. Nos demais animais dos Grupos B e C, e epicárdio subjacente ao látex apresentava-se ligeiramente espessado, permitindo visibilizar os vasos coronários com facilidade. Microscopicamente, identificaram-se algumas áreas com denso infiltrado linfo-plasmocitário, proliferação fibroblástica e vascular; em outras, os fibroblastos circunscreviam fendas com revestimento mesotelial, indicativas de regeneração irregular do pericárdio. Não se observou infecção local nem alteração do leucograma e ao ECG, apenas inversão da onda T, em todos os grupos. CONCLUSÃO: A membrana de látex natural mostrou-se adequada para a substituição parcial do pericárdio de cães, em observação de até 345 dias, propiciando a regeneração do pericárdio nativo.
... Several natural barriers such as peritoneum, omentum, and amnion [13,14], and synthetic physical barriers such as silicone, polytetrafluoroethylene, cellulose, polyvinyl alcohol, and polyester derivatives also have been tried. Some of them were tried in the retrosternal space [3][4][5][15][16][17][18]. The basic mechanism of physical barriers for preventing adhesion is separating the injured tissue surface from the adjacent tissues [19]. ...
... Some of them were tried in the retrosternal space [3][4][5][15][16][17][18]. The basic mechanism of physical barriers for preventing adhesion is separating the injured tissue surface from the adjacent tissues [19]. Physical barrier methods have been tried for decades to prevent postoperative tissue adhesion [3][4][5][15][16][17][18]20]. Among them, there are film barriers, solution barriers, and recently developed solgel transition barriers. ...
This study was performed to examine the efficacy and safety of a hyaluronan solution (Guardix-SL) and a temperature sensitive poloxamer solution/gel material (Guardix-SG) on the prevention of pericardial adhesion in rabbits.
A total of 60 rabbits were divided into three groups according to material applied after epicardial abrasion: the control group (group CO), the Guardix SL group (group SL), and the Guardix SG group (group SG). The ejection fraction and the presence of pericardial effusion were evaluated by echocardiograms at the immediate postoperative period and 2 wk after the surgery. The adhesion was evaluated macroscopically and microscopically 2 wk after the surgery.
In the group SG, mild pericardial effusions were observed only at the immediate postoperative period in 10 out of 20 rabbits with an insignificant reduction of the ejection fraction. Group CO had a significantly higher macroscopic adhesion and fibrosis score than did groups SL and SG (P < 0.001), and group SL had a significantly higher adhesion score than did group SG (P = 0.045). Inflammation score and the expression of anti-macrophage antibody in group CO were higher than those in groups SL and SG, although the differences were not significant.
Guardix-SL and Guardix-SG effectively reduced the adhesion formation, and Guardix-SG is more effective than Guardix-SL for preventing adhesion. However, Guardix-SG showed a potential disadvantage of decreasing the ejection fraction, although this was statistically insignificant. Further study to verify the appropriate dosage to maximize the therapeutic effect without decreasing the heart function is needed.
... Adhesion scoring was performed according to a previous report. 20 Briefly, Grade 0 indicates no adhesion, Grade 1 indicates light adhesion that could be bluntly dissected, Grade 2 indicates stronger adhesion, and Grade 3 indicates dense adhesion requiring sharp dissection. ...
As most surgical treatments pose a risk of tissue adhesion, methods to prevent adhesion are needed across various surgical fields. In this study, we investigated the use of a decellularized pericardium with fibrin glue to prevent rat heart adhesion. Porcine pericardia were decellularized by a high‐hydrostatic pressure method. Cells adhered to the resulting pericardial extracellular matrix (ECM) during an in vitro cell‐seeding test, but fibrin‐coated pericardial ECM showed reduced cell adhesion. In a rat surgical model of heart adhesion, the fibrin‐coated pericardial ECM did not adhere to the heart and mesothelial cell adhesion was observed on the ECM surface. Notably, the anti‐adhesion effect of fibrin‐coated pericardial ECM was observed 4 weeks after surgery. These results support the utility of fibrin‐coated pericardial ECM as an adhesion prevention material for cardiovascular surgery. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res B Part B: Appl Biomater 00B: 000–000, 2018.
... The morphology was studied by a semiquantitative method [9,13,15]. During macroscopic examination, the severity of pericardial adhesions was scored using a 4-point scale [11] and "visibility" of coronary arteries by 3-point scale [9]. Microscopic examina- tion was carried out on total heart cross-sections; the severity of inflammation and epicardial fibrosis was evaluated by a 4-point scale [13]. ...
Biodegradable film compositions based on natural biopolymer gelatin with immobilized colchicine were prepared and their efficiency in prevention of the adhesion process in the pericardium was evaluated on rabbit model of postoperative pericarditis. The use of gelatin-based biodegradable film compositions significantly reduced the intensity of adhesion formation in the pericardial cavity, while immobilization of anti-inflammatory drug colchicine amplified their anti-adhesion activity.
... The subjects were sacrificed at the end of either three weeks (groups 1 and 3) or six weeks (groups 2 and 4) using the same lethal dose of ketamine and xylazine, and then the mediastinum was reached via a sternotomy. The adhesion level was graded macroscopically by a surgeon who was blinded to the animal groups using the scale described in the study by Heydorn et al. [16] (0= no adhesion, 1= adhesion which could be separated easily by finger dissection, 2= intermediate adhesion strength, and 3= adhesion which necessitated sharp dissection) ( Figure 1). The heart was removed along with its pericardium, and then the myocardium and epicardium specimens, including the adhesions, were taken. ...
Amaç: Bu çalışmada pelvik yapışıklıkları önlemede etkinliği kanıtlanmış biyoemilebilir polilaktid bariyerin ameliyat sonrası perikardiyal yapışıklıkları önlemedeki etkinliği bir hayvan modelinde değerlendirildi. Ça lış ma pla nı: Kırk Yeni Zelanda beyaz tavşanı eşit olarak kontrol ve tedavi gruplarına ayrıldı. Deneklere sol anterior torakotomi ve parsiyel perikardiyektomi sonrası epikardiyal abrazyon uygulandı. Kontrol gruplarında (grup 1 ve 2) retrosternal yapışıklıklara izin vermek için perikard açık bırakıldı. Tedavi gruplarında ise (grup 3 ve 4) perikardiyal defekt 0.02 mm biyoemilebilir polilaktid bariyer ile kapatıldı. Ameliyat sonrası makroskopik ve mikroskopik değerlendirmeler gruplar hakkında bilgisi olmayan değerlendirmeciler tarafından grup 1 ve 3'te üçüncü haftanın sonunda, grup 2 ve 4'te ise altıncı haftanın sonunda yapıldı. Bul gu lar: Makroskopik ve histopatolojik değerlendirmeler kontrol ve tedavi grupları arasında adezyon gelişimi açısından anlamlı farklılık olmadığını gösterdi. Ancak polilaktid bariyer tedavi gruplarında mezotelyum benzeri hücre tabakasının gelişimini destekledi. So nuç: Polilaktid bariyer mezotel hücre tabakasının rejenerasyonuna yardımcı olsa da perikardiyal yapışıklıkların gelişimini önlememektedir. Anah tar söz cük ler: Biyoemilebilir polilaktid bariyer; kalp cerrahisi; perikardiyal yapışıklıklar. ABSTRACT Background:This study aims to evaluate the efficacy of
... Four months later, the animals underwent repeat sternotomy under a similar anaesthesia protocol. The surgeon graded adhesion (from Grade 0: no adhesion to Grade 3: dense adhesions requiring sharp dissection) formation according to the score defined by Heydorn et al. [3]. One score was established for each animal. ...
Reduction in mediastinal adhesions is an issue in cardiac surgery. To evaluate a porcine-bioengineered collagen membrane (Cova™
CARD) intended to promote tissue regeneration, 18 sheep underwent a sternotomy and a 30 min period of cardiopulmonary bypass.
They were divided into three equal groups: pericardium left open, placement of an e-polytetrafluoroethylene membrane (Preclude®) taken as a non-absorbable substitute comparator and placement of the absorbable Cova™ CARD membrane. Four months thereafter,
the study animals underwent repeat sternotomy and were macroscopically assessed for the degree of material resorption and
the intensity of adhesions. Explanted hearts were evaluated blindly for the magnitude of the inflammatory response, fibrosis
and epicardial re-mesothelialization. The bioengineered membrane was absorbed by 4 months and replaced by a loosely adherent
tissue leading to the best adhesion score. There was no inflammatory reaction (except for a minimal one in an animal). Fibrosis
was minimal (P = 0.041 vs Preclude®). The highest degree of epicardial re-mesothelialization, albeit limited, was achieved by the bioengineered group in which
five of six sheep demonstrated a new lining of mesothelial cells in contrast to two animals in each of the other groups. This
collagen membrane might thus represent an attractive pericardial substitute for preventing post-operative adhesions.
Background
The value of polytetrafluoroethylene (PTFE) surgical membrane as a pericardium substitute in patients who undergo reoperation for rheumatic valve disease is reported in this observational study.
Methods
PTFE was used for pericardial closure in 56 rheumatic valve patients. During reoperation of seven cases, adhesions were classified as none, minimal, moderate to severe and scored in the sections of heart. Data found at reoperations were collected prospectively in all patients.
Results
Seven of 56 patients reoperated mean period of 67.1 ±23.4 (SD) months later. No infection, complication and operative or late death attributable to the membrane were observed. There were two right ventricular, three minimal right atrial and one innominate vein lacerations during resternotomy and all of them were controlled. During histological examination, a microscopically significant foreign body reaction was found.
Conclusion
PTFE membrane produced an undesirable fibrous membrane that obscured the epicardial anatomy and hardened the dissection in patients with rheumatic heart disease.
Incorporation of surrounding tissues after implantation of synthetic vascular prostheses potentially varies in accordance with implanted prostheses. To evaluate post-implant tissue incorporation, we examined surgical, histological and ultrastructural findings after implantation in animal models. Three types of commercially available prostheses were tested (Gelweave™; Group G, J Graft SHIELD NEO®; Group J and Triplex®; Group T). Prostheses were implanted into Sprague–Dawley rats subcutaneously or sutured on abdominal aorta of Japanese white rabbits. The tissues were surgically examined for adhesion and were subjected to histological evaluations for cellular and tissue infiltration and ultrastructural observations by scanning electron microscopy (SEM). Group G exhibited less tendency in adhesion formation in early phase (rat: G vs J, P < 0.0001; G vs T, P < 0.0001/rabbit: G vs J, P < 0.0001; G vs T, P = 0.059). In late phase, Group J showed highest adhesion (rat: G vs J, P = 0.0004; J vs T, P = 0.015/rabbit: G vs J, P = 0.0015; J vs T, P = 0.0044). In group G, a gap was observed between implants and surrounding tissues forming capsulation, whereas other groups exhibited tissue infiltration inside of the implants wall which were also confirmed by SEM. The tissue permeation toward the implants and adhesion was positively correlated (P < 0.0001). Surrounding tissue conformation varied in accordance with the type of prostheses. It is desirable to elucidate characteristics of each prosthesis to select suitable grafts for each patient to achieve a better surgical outcome.
Five different materials, equine pericardium, bovine pericardium, porcine pericardium, silicon rubber and expanded polytetraf luoroethylene (EPTFE) surgical membrane, were evaluated experimentally to find a suitable pericardial substitute to prevent pericardial adhesions. Xenopericardiums were found to have higher levels of adhesion and epicardial reaction. Signs of organization were found in these materials histologically. It was suggested that xenopericardiums were not suitable for prevention of pericardial adhesions. The silicon rubber had significantly lower levels of adhesion compared with the equine pericardium, the porcine pericardium and the EPTFE membrane. However this material had the most significant epicardial reaction. So it was considered that silicon rubber was not acceptable in such cases as aortocoronary bypass resurgery. The EPTFE surgical membrane had no superiority for adhesion or epicardial reaction, but it seemed to be useful because no sign of organization was found in this material histologically.
The formation of adhesions following cardiothoracic surgery places the mediastinal structures and grafts at risk of catastrophic injury [91] during a second sternotomy, making it a bloody, time-consuming, and hazardous procedure [20, 51]. Over 360 000 cardiac procedures are performed annually in the United States [37, 88] up to 10% of which are reoperations [15, 26, 41].
The polytetrafluoroethylene Gore-Tex Surgical Membrane has been used at our Institution for pericardial closure, temporary skin closure after cardiac operations and to close the retroperitoneum over aortic vascular prostheses. Five Gore-Tex membranes have been available for examination. Light microscopy showed that neither tissue ingrowth nor bacterial growth have been developed in any of the samples studied. In addition, only a minimal epicardial reaction in the area beneath the membrane was seen in one of the cases of pericardial closure. This material seems to act as an adequate substitute for biological barriers such as the pericardium and the skin.
The Gore-Tex Surgical Membrane* is a very thin sheet of expanded polytetrafluoroethylene that has initially been designed as a pericardial substitute in an attempt to reduce or minimize adhesions formation to provide a safe and efficient plane of dissection which is of utmost interest when dealing with a cardiac reoperation. In addition, we have been using it also as a substitute of other biological barriers such as the skin and the retroperitoneum. In the last few years, some information about clinical experiences with the GSM has been available, however very few information has been collected about GSM explants1–3. We have been able to collect some GSM explants and histological analysis has been performed to ascertain if there has been tissue penetration or bacterial colonization.
The introduction of prosthetic materials has been an important advance in the surgical treatment of large abdominal wall defects. Since 1987 we performed a new technique using two prostheses on 24 patients with large abdominal wall defects. The first patch, the 'surgical membrane', was placed intraperitoneally as a peritoneal substitute. The second patch, the 'soft tissue patch', was placed externally the 'surgical membrane'. The operative mortality was 0. Morbidity was 8.3% (2 out of 24). Follow-up, ranged from 4 months to 3 years, showed no long-term complications and no recurrences. The excellent results clearly indicate that the use of our technique for the surgical treatment of large abdominal wall defects should be advocated.
Retrosternal epicardial adhesions may cause significant injuries to the heart and great vessels in cases that require reoperation. We used a varity of agents to prevent the occurence of adhesions and observed different results. An experiment with 3 groups of rabbits with 10 rabbits in each group was prepared to investigate the roles of Dexamethazone-Ringer Lactate (DM-RL) combination and Hyaluronic Acid-Carboxylmethyl Cellulose (HA-CMC) in preventing adhesions. First group (Group I) was the control group, the second (Group II) was tested for DM-RL and the third group (Group III) was tested for HA-CMC. These agents were topically applied to the epicardial region after the sternotomy and pericardiotomy phases. The adhesion score was significantly higher in the first group than the adhesion score in the second group (p<0.05). The first group had significantly higher chronic inflammatory cell response, adhesion score and adhesion percentage than the third group (p<0.05). In these groups, no differences of fibrosis and acute cell response were observed on statistical terms (p>0.05). The second group had higher acute inflammatory cell response and adhesion percentage than the third group in statistical terms (p<0.05). There was no statistically differences of fibrosis, adhesion score and cronic inflammatory cell response in these groups. We have found that the use of bioresorbable membrane containing DM-RL and HA-CMC clearly decreases the postoperative epicardial and retrosternal adhesions. The use of membrane containing HA-CMC is found to be more effective than the use of membrane containing DM-RL.
Adhesion formation and fibrosis represent a major complication of surgical intervention. Reducing the morbidity associated with adhesions requires an understanding of the mechanisms underlying their formation. Since increased levels of transforming growth factor-beta1 (TGFbeta1) have been associated with inflammation and adhesion production, we investigated the requirement of TGFbeta1 in peritoneal adhesion formation utilizing mice carrying a targeted disruption of the TGFbeta1 allele. Mice that were either wild-type (+/+), containing two normal alleles of TGFbeta1, or heterozygous (+/-) for the TGFbeta1 null allele received injections of magnesium silicate (talc),and the extent of abdominal adhesions was determined utilizing a standard grading score. Wild-type (+/+) animals had at least twofold more TGFbeta1 protein in peritoneal fluids at 2 h posttrauma compared to heterozygous (+/-) mice (727 vs. 243pg TGFbeta1/mg protein by enzyme-linked immunosorbent assay (ELISA) in +/+ and +/- mice, respectively), ...
The origins, syntheses, variable composition and physical properties of bioelastic materials are discussed. The latter includes their capacity to undergo inverse temperature transitions to increased order on raising the temperature and to be designable to interconvert free energies involving the intensive variables of mechanical force, temperature, pressure, chemical potential, electrochemical potential and light.
Bioelastic materials include analogues and other chemical variations of the viscoelastic polypeptide, poly(Val-Pro-Gly-Val-Gly), and cross-linked elastomeric matrices thereof. This parent material has been shown to be remarkably biocompatible; it can be minimally modified to vary the rate of hydrolytic breakdown; it can contain enzymatically reactive sites; and it can have cell attachment sites included which promote excellent cell adhesion, spreading and growth to confluence.
One specific application is in the prevention of postoperative adhesion. There are some 30,000,000 per year surgical procedures in this country and a large portion of these would benefit if a suitable material were available for preventing adhesions. Bioelastic materials have been tested in a contaminated peritoneal model, and promising preliminary studies have been carried out in the rabbit eye model for strabismus surgery. In the peritoneal model, 90% of the 29 control animals exhibited significant adhesions; whereas, only 20% of the 29 animals using gas sterilized matrices had significant adhesions. On the basis of this data, it appears that cross-linked poly(VPGVG) is an effective physical barrier to adhesion formation in a trauma model with resulting hemorrhage and contamination.
The potential use of bioelastic materials as a pericardial substitute following the more than 400,000 open heart surgeries per year in the U.S. is under development beginning with the use of bioelastic matrices to prevent adhesions to the total artificial heart being used as a bridge to heart transplantation such that the site will be less compromised when receiving the donor heart.
An experiment was designed to find the suitable acellular bovine pericardium (ABP) patch in pericardial cavity reconstruction and to evaluate the effect of sodium hyaluronic acid (NaHA) on inflammatory reaction in prevention of pericardial adhesions. The pericardial adhesion model was established in 20 rabbits, weighing from 3.2 to 3.6 kg. Groups were classified as follows: Group A (n = 5), the control group, the pericardium was directly closed; Group B (n = 5), 0.15% glutaraldehyde-treated ABP (low cross-link degree); Group C, 0.3% glutaraldehyde-treated ABP (middle cross-link degree); Group D, 0.15% glutaraldehyde-treated ABP + NaHA solution. Blood samples were collected at 6 h, 24 h, 3 days, and 5 days, to assay postoperative inflammatory reaction. The tenacity and severity of adhesions were evaluated 2 months after operation, by macroscopic and microscopic examinations, and Q-PCR (real-time quantitative polymerase chain reaction) test was used to quantitatively analyze the associated genes with adhesion. Pericardium regeneration was demonstrated by immunohistochemical technique to identify mesothelial cells. In Group D, the serum concentration of tumor necrosis factor-α (TNF-α) was significantly lower in the early postoperative period, and the mean adhesion score (adhesion between the epicardium and ABP) was significantly lower compared with the control group (Groups D vs. A: 0.20 ± 0.45 vs. 2.00 ± 0.71, P = 0.009*). The signs of degradation of the ABPs were observed 2 months postoperation in Groups D and B. Immunohistochemically, the positive cytokeratin AE1 staining results demonstrated the relatively total regeneration of the pericardium in Group D. Signs of regeneration were observed in Group D. Compared with the control group, the level of TGF-β2 in Group D was significantly lower (0.00132 ± 0.00114, P = 0.022*). The TGF-β3 level was statistically significant, being highest in Group D (0.00805 ± 0.00136, P = 0.029*). The mean quantity of Smad6 in Group D was also lower than the other groups. Low cross-link degree ABP may be an efficient physical block between the epicardium and the sternum and also an ideal scaffold for pericardial tissue regeneration, whereas combined use with NaHA may significantly reduce postoperative pericardial adhesions. The signal transduction pathway of transforming growth factor-β (TGF-β) and Smad6 may play a key role in the formation of pericardial adhesion.
SUMMARY The study was designed as a comparative, evaluator-blinded, randomized, parallel clinical trial to determine the safety of REPEL-CV for reducing post-operative cardiovascular adhesions following adult cardiothoracic surgery. Safety was evaluated by analysis of adverse events, clinical laboratory results, and concomitant medication. The REPEL-CV treated patients showed similar profiles for these safety parameters as the non-treatment control group. Based on the safety measures monitored in this study, it was concluded that REPEL-CV does not present an additional safety risk to the adult patient population studied. Based on the above, the FDA approved the initiation of a feasibility study to assess the safety and efficacy of REPEL-CV in pediatric patients scheduled to undergo staged sternotomy procedures. This study will be communicated in the accompanying paper.
SUMMARY The study presented is a comparative, evaluator-blinded, randomized, parallel, single center clinical trial to determine the safety and effectiveness of REPEL-CV for reducing post-operative adhesions following pediatric cardiothoracic surgery. This feasibility study, which enrolled 13 patients, was conducted to compare REPEL-CV treatment to a non-treatment control. The effectiveness data available from this feasibility study suggest that REPEL-CV reduces the extent and severity of post-operative adhesions following pediatric cardiothoracic surgery. The safety data show that the REPEL-CV treated patients did not develop adverse events unexpected for their respective surgical procedure and the adverse events profiles were similar between the treated and control groups. Based on the safety measures monitored in this study, it was also concluded that REPEL-CV did not present an additional safety risk to the pediatric patient population studied. Based on the above, the FDA and several European Regulatory Authorities approved the initiation of ongoing multi- center studies. These ongoing studies reflect the design and patient population of the above neonate study.
Background:
Postoperative retrosternal adhesion increases the risk of cardiac injury during cardiac reoperation. We created a novel biodegradable glue called "Lydex" that is derived from food additives. The purpose of this study is to evaluate this new biomaterial's biocompatibility and its preventive effect on retrosternal adhesion.
Methods:
We performed a median sternotomy and anterior pericardiectomy on Japanese white rabbits, and then closed the chest (control, group 1; n = 12), implanted an expanded polytetrafluoroethylene membrane (group 2; n = 12), or applied Lydex (group 3; n = 12) before closure. After 4 weeks, we evaluated macroscopic adhesion (each group; n = 6) and microscopic findings for fibrosis and macrophage infiltration (each group; n = 6).
Results:
In group 3, the retrosternal adhesion score was significantly lower than in group 1 (P = .0022). There was no significant difference between groups 2 and 3. The fibrotic area ratio was significantly lower in group 3 than in groups 1 and 2 (P < .001 vs group 1; P < .001 vs group 2). In group 3, the macrophage count was significantly lower than in group 2 (P < .001) and almost equal to that in group 1.
Conclusions:
Our findings indicate that Lydex reduces retrosternal adhesion and attenuates the progression of fibrosis with excellent biocompatibility. Lydex is a next-generation substance for safer cardiac reoperation, with excellent capability for preventing adhesion, biocompatible and biodegradable properties, and lower potential for viral infections related to human plasma or other animal-derived products.
Background:
N-acetylcysteine (NAC), a precursor of reduced glutathione, has been in clinical use primarily as a mucolytic. In addition, NAC is well known for their free radical scavenging and antioxidant properties. Increasing of reactive oxygen products occurring during cardiac surgery can play an important role in postoperative adhesion formation. We investigated to the efficacy of the NAC for postoperative pericardial adhesions.
Methods:
Sixteen New Zealand white rabbits (2.5-3 kg) were used and categorized into two groups including study (use of NAC) and control groups. In both groups, the pericardium was opened longitudinally, and the exposed epicardial surfaces were abraded with dry gauze. The rabbits were divided into two groups: Group 1 was treated with the sponge, which impregnated with NAC solution, (10%, 300 mg/3 ml) and applied over the abraded epicardium for 5 min (n=8). Group 2 was the control, and the sponge, which was impregnated with 3-ml isotonic NaCl solution (0.9%), was applied onto the surface of the abraded epicardium for 5 min (n=8). After a period of 2 weeks, the animals were sacrificed. The scores of adhesion were graded by macroscopic examination, and the pericardial tissues were analyzed microscopically in point of inflammation and fibrosis.
Results:
In Group 1, the adhesion scores were significantly lower compared with the control group [Group 1 vs. 2; 1 (1-2) vs. 3 (2-3), P<.001]. No significant difference was found between the groups in terms of the severity of inflammation [Group 1 vs. 2; 1.5 (1-3) vs. 2.5 (1-3), P=.083]. There was a difference between groups in terms of the degree of fibrosis [Group 1 vs. 2; 2 (1-2) vs. 3 (2-3), P=.007].
Conclusions:
The use of NAC for preventing postoperative pericardial adhesions was reduced to adhesion and fibrosis scores in an experimental rabbit model. There was no statistically significant difference between groups in terms of inflammatory scores. The NAC effectively prevented the formation of pericardial adhesion.
Background:
Mitomycin-C has been in clinical use primarily as a chemotherapeutic agent and is well known for antifibrotic properties. It has been widely used to prevent postoperative fibroblast proliferation and reduce scar adhesion in ophthalmologic and otolaryngologic operations. We investigated the efficacy of mitomycin-C in reducing postoperative pericardial adhesions in a rabbit model.
Methods:
New Zealand white rabbits were used and categorized into 2 groups, study (use of mitomycin-C) and control. Group 1 (n = 8) was treated with a sponge impregnated with mitomycin-C solution that was applied over the abraded epicardium. In group 2 (control group), the sponge was impregnated with 0.9% isotonic NaCl solution and was applied with the same protocol as the mitomycin-C-impregnated sponge in group 1 (n = 8). Rabbits were humanely killed at a mean of 2 weeks. The scores of adhesion were graded by macroscopic examination, and the pericardial tissues were analyzed microscopically in terms of inflammation and fibrosis.
Results:
In group 1, the adhesion scores were significantly lower than the control group's. No significant difference was found between the groups in terms of the severity of inflammation. There was a difference between groups in terms of the degree of fibrosis.
Conclusions:
The use of mitomycin-C to prevent postoperative pericardial adhesions reduced adhesion and fibrosis scores in an experimental rabbit model. However, efficacy in reducing inflammation was not demonstrated.
Radical pelvic surgery has well-defined side effects, many of which may be related to the formation of pelvic adhesions. The effectiveness of different agents at limiting the formation of postradical pelvic surgery adhesions (PRPSA) has been variable to date. Use of a barrier could be beneficial not only by limiting adhesion formation but by acting as a “pelvic lid” to elevate the bowel out of a radiation treatment field and therefore limit subsequent radiation injury and associated fistula formation. We investigated the ability of the Gore-Tex Surgical Membrane (Gore-SM) to inhibit PRPSA in 20 adult female hogs undergoing radical hysterectomy, bilateral salpingo-oophorectomy, and resection of pelvic peritoneum. After completion of the radical resection, animals were randomized to either no attempt at covering the peritoneal defect or covering it and a 1-cm margin of intact peritoneum with a tailored sheet of Gore-SM. The membrane was secured in place using a continuous running 4-O Prolene suture around the perimeter. No intraoperative deaths occurred. No animal evidenced signs of bleeding, infection, bowel obstruction, or abscess formation. Four weeks after the initial surgery, the animals were again anesthetized, exploratory celiotomy was performed, and adhesions were quantified with specific note being made of any segments of small bowel that were adherent into the pelvis. Animals were then sacrificed. Adhesion scores for the Gore-SM-treated animals (n = 10; mean, 0.14 ± 0.12; median, 0.21) were significantly less than those of animals with the noncovered pelvis (n = 10; mean, 1.33 ± 0.41; median, 1.42; P < 0.001). Similarly, significantly fewer animals treated with Gore-SM had small bowel loops adherent in the pelvis when compared to control animals (10% vs 70%; P < 0.01). In this model, meticulously suturing the membrane in place with continuous permanent suture, the Gore-SM was an effective barrier for postoperative adhesion prophylaxis and successfully limited small bowel adherence into the pelvis.
Reduction of sternal adhesions is still an issue in cardiac surgery. To evaluate a new fibrillar porcine collagen absorbable membrane (Cova CARD), 16 sheep underwent a sternotomy followed by scratching of surface of the heart. They were then divided into three groups: pericardium left opened (n=4), placement of Seprafilm), the reference absorbable substitute (hyaluronic acid and carboxymethylcellulose, n=6) or of Cova CARD membrane (n=6). Four months thereafter, the animals underwent repeat sternotomy and were macroscopically assessed for the degree of resorption of the material and the intensity of adhesions. Explanted hearts were blindly evaluated for the magnitude of the inflammatory response and fibrosis. The Cova CARD membrane was almost totally absorbed by four months and replaced by a loosely adherent tissue. There was no inflammatory reaction and both the extent and density of fibrosis were minimal. The composite score (median [min;max]) integrating tightness of adhesions and histological findings of inflammation and fibrosis was two-fold lower in the Cova CARD than in the Seprafilm) group (2.0 [0;3.5] vs. 5.5 [3;7], P=0.01 by Wilcoxon test). The Cova CARD membrane might represent an attractive pericardial substitute for preventing postoperative adhesions in cardiac surgery.
Orientador: Francisco Diniz Affonso da Costa Dissertação (mestrado) - Universidade Federal do Paraná, Setor de Ciências da Saúde
To evaluate the efficacy of melatonin in preventing postoperative pericardial adhesions, 12 single breed dogs were randomized equally into experimental (melatonin) and control groups. After ketamine anesthesia, a vertical midsternal incision was done and the parietal pericardium of the inferior site of the heart was opened vertically. To promote adhesion formation, abrasions were created on both parietal and visceral pericardial surfaces in an area of 2 cm2 with two vertically reciprocal movements of dry gauze. In the melatonin group, 5% ethanol plus 10 mg/kg melatonin in 10 ml NaCl and, in control group, 10 ml NaCl dilution vehicle containing 5% ethanol was instilled intra-pericardium on to the abrasion sites. After a 6-week recovery period, the animals were evaluated for grading of adhesion formation by an examiner blinded to the groups. The extent of adhesions was graded from 0 (no adhesion) to 3 (total involvement of the traumatized area). The results showed that adhesion scores were significantly lower in melatonin group (1.00+/-0.63) compared with controls (2.66+/-0.51); P=0.001. We conclude that melatonin administration effectively reduced postoperative pericardial adhesions in dogs. The use of melatonin in the prevention of pericardial adhesion formation in human subjects warrants further investigations.
Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically.
Pericardial adhesions after cardiac operations are a widely known phenomenon. They may severely complicate reoperations, making reentry hazardous, increasing bleeding, and prolonging the operation time. The anatomic orientation and visibility of both bypass grafts and coronary arteries are also impaired. With the aim of minimizing pericardial adhesions after cardiac operations, we studied the course of tissue regeneration after implantation of a new absorbable patch made from poly-hydroxy-butyrate. A total of 23 sheep were studied. Of these, 18 formed the test group and five served as control animals. The animals were killed at intervals of 2 to 30 months after the operation. In 14 of the 18 test animals no adhesions developed. In three animals loose adhesions were found, and in one with signs of postoperative infection there were moderate, generalized adhesions. All control sheep showed moderate adhesions; no infection was noted in this group. Light microscopy in the test group revealed a layer of mesothelium-like cells facing the epicardial side; this was already present in the early specimens. Poly-hydroxy-butyrate appeared to be slowly phagocytosed by polynucleated macrophages, which were still found occasionally in the late samples. Lymphocytes and platelets were rare. Scanning electron microscopy showed, on the epicardial side of the regenerated tissue, a mesothelium-like lining that completely covered the underlying collagen layer. The surface cell morphology grossly resembled that of native pericardium. It was concluded that in this animal model poly-hydroxy-butyrate pericardial patches decreased adhesions and preserved coronary anatomy. The findings in the control group demonstrated that pericardial surgery in the sheep was associated with adhesion formation.
We investigated the ability of Gore-Tex Surgical Membrane (Gore-SM) to inhibit PRPSA formation in 10 adult female canines undergoing radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and resection of the pelvic/abdominal peritoneum. At the time of surgery, one-half of the pelvic/abdominal peritoneal defect was covered with a tailored single layer of the Gore-SM. The membrane was sutured into place with 3-O Dexon in an interrupted manner. Each animal served as its own internal control. No operative/postoperative deaths or postoperative complications occurred. Four weeks postsurgery, euthanasia was effected, necropsy performed, and adhesions quantified. Adhesion scores for the Gore-SM-covered areas (n = 10; mean score, 2.76 +/- 1.47; median, 2.46) were significantly higher than those for control areas (n = 10; mean score, 1.46 +/- 2.13; median, 1.81; P = 0.01). Adhesions to the Gore-SM occurred at wrinkles in or at the edges of the membrane. In contradistinction to the findings of other investigators using different animal models, the Gore-SM appears to increase PRPSA in this unique model.
The difficulties of reoperation owing to adhesions are well known. Clinical attempts to solve this problem using synthetic materials or glutaraldehyde-fixed pericardial xenograft have been less than satisfactory. Although experimental animal results have been good, they have not considered the influence of cardiopulmonary bypass (CPB) on adhesion formation. This study addressed the influence of CPB on the formation of adhesions and evaluated biodegradable polyglycolic acid as a material to reduce adhesions and as a pericardial substitute. Forty-five weanling sheep received implants of pericardial xenograft and polyglycolic acid with and without CPB. The pericardial xenograft showed no adhesions when implanted without CPB, but severe adhesions formed and a thick fibrinous layer covered the heart when CPB was used, making identification of coronary arteries at reoperation very difficult. The polyglycolic acid mesh implanted without CPB was absorbed and replaced with newly formed host collagen. With CPB, the polyglycolic acid was more rapidly absorbed, and a thinner layer of host collagen formed. Therefore, future animal studies must include CPB. In agreement with reported clinical results, glutaraldehyde-fixed pericardial tissue implanted with CPB resulted in severe epicardial reaction and therefore is not an ideal pericardial substitute.
Many thoracic surgeons have used pericardial substitutes to reduce the risk of reoperation, but there have been few reports of these procedures. Therefore, we used a questionnaire to gather information on experience with use of pericardial substitutes and to document the findings at reoperation. A six-question survey was sent to 2,344 members of The Society of Thoracic Surgeons, requesting surgeons to list their experience with pericardial substitutes and at reoperation in patients with these substitutes in place. Of the 634 surgeons who responded to the survey, 120 reported the insertion of 3,828 pericardial substitutes. Two hundred thirty-six reoperations were reported by 89 surgeons. None of the pericardial substitutes was reported to be completely successful in facilitating reoperation. The experience with polytetrafluoroethylene (PTFE) pericardial substitutes was reported to be significantly more satisfactory than that with all other substitutes (p = 0.0004 by chi-square analysis), but 14% of surgeons who used PTFE said they were dissatisfied at reoperation. Based on the results of this survey, we suggest caution, careful documentation, and long-term follow-up studies before widespread use of pericardial substitutes can be recommended.
Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical applications of solutions containing hyaluronic acid (HA) have been shown to reduce adhesions following abdominal and orthopedic surgery. The mechanism by which HA solutions prevent adhesion formation is unknown, but may be due to a cryoprotective effect on mesothelial surfaces, thus limiting intraoperative injury. In this study we tested the efficacy and safety of HA coating solutions for the prevention of postoperative intrapericardial adhesion formation.
Patients who undergo repair of congenital heart defects have a high probability of eventually needing a repeat operation. In such cases, use of a pericardial substitute can preclude adhesion formation, thereby helping to avert the complications of a repeat sternotomy. This report describes our use of the GORE-TEX polytetrafluoroethylene surgical membrane in 321 patients who underwent repair of congenital heart disease at our hospital between May of 1989 and December of 1992 (these cases account for 37.1% of all such repairs performed during this period). The patients' ages ranged from 2 days to 31 years (mean, 5.9 years). Eighty-eight patients (27.4%) had at least 1 previous median sternotomy, and 234 (73.0%) had a moderate to high probability of reoperation. Seventy-eight patients (24.3%) received a homograft, which was positioned extracardially in 63 cases. During a maximum follow-up period of 43 months (mean, 26 +/- 5.6 months), 11 patients died, for an overall mortality of 3.4%. In no case was death attributable to membrane-related complications. Postoperative complications were encountered in 12 patients (3.7%), 10 of whom required an early repeat thoracotomy. One patient had mediastinitis, for an incidence of 0.3% (in contrast to 0.2% in 864 patients who underwent similar repair without the use of a surgical membrane). No complications were encountered in the 27 patients in whom the membrane was implanted during delayed sternal closure. Seventeen patients (5.5% of the survivors) underwent a repeat sternotomy, for further correction of congenital heart defects, a mean of 20 months after the original repair. At reoperation, major complications were encountered. Although the number of reoperations was low, we conclude that use of the polytetrafluoroethylene surgical membrane for pericardial closure in children is a safe procedure that helps prevent complications at reoperation.
Cardiac injury during sternal reentry to the heart is a rare but dangerous complication of cardiac reoperations. Positioning a pericardial flap between the heart and sternum at the time of the initial operation may consistently facilitate cardiac reoperation by providing a reliable plane of dissection and by reducing adhesion formation.
The use of glutaraldehyde as a fixative in bioprostheses and drug delivery matrices is reviewed. The chemistry of glutaraldehyde cross-linking and its effect on the biological performance of a number of bioprostheses such as tissue heart valves, vascular grafts, pericardial patches, tendon grafts and drug delivery matrices are examined.
Surgical adhesions are a major cause of morbidity and mortality. The ideal barrier agent will both minimize adhesions and provide a milieu for the regeneration of the mesothelium lining of the abdominal and thoracic cavities. N,O-Carboxymethylchitosan (NOCC), a derivation of chitin that markedly reduces adhesions, may function to modulate intracellular signals such as growth factors and cytokines in the inflammatory exudate. Since transforming growth factor-beta is implicated in the fibrotic process, we investigated the possibility that NOCC's effects on adhesion formation reflects a modulation of TGF-beta activity. Using a biological assay for inhibition of cell proliferation to detect TGF-beta activity, we demonstrate that NOCC suppresses the levels of an inhibitor of cell proliferation released into serum and peritoneal exudates after cecal abrasion in the rat. However, this activity was distinct from known forms of TGF-beta as determined using both TGF-beta-neutralizing antisera and a TGF-beta-resistant cell proliferation assay. Thus at least one potential effect of NOCC involves a mechanism distinct from TGF-beta inhibition.
The purpose of this study was to test the efficacy of three bioresorbable films of polyethylene glycol (EO) and polylactic acid (LA) (EO/LA = 1.5, 2.5, and 3.0) in the prevention of adhesion formation between the epicardium and the sternum (retrosternal adhesions) in a rabbit model. Retrosternal adhesions were generated by sternotomy, pericardiotomy, and abrasion of the anterior epicardium. The adhesion barrier was placed between the epicardium and the sternum and sutured to the edge of the pericardium. Epicardial adhesions were evaluated 14-20 days later by assessing the area of the epicardium covered by adhesions. In the control rabbits, tenacious adhesions were observed between sternum and the central portion of epicardium (portion exposed through the pericardiotomy) which were difficult to dissect. When a bioresorbable film was placed over the pericardium, adhesion formation at the central strip of the epicardium (area between the sternum and the epicardium exposed through the pericardium) could be reduced or prevented. At this site, the areas of adhesion formation were 0% (EO/LA = 1.5), 8.4 +/- 2.8% (EO/LA = 2.5), and 5.6 +/- 4.7% (EO/LA = 3.0) of the central strip, significantly less than that observed in the control group, 78.0 +/- 5.8% (P < 0.01). At the anterior left and right and posterior apex of the heart (sites where the film was not placed), there were no differences between control and treatment groups. The films were completely resorbed at the time of necropsy in group EO/LA = 2.5 and 3.0. Small pieces of film were observed in group EO/LA = 1.5. In conclusion, the bioresorbable films [EO/LA = 1.5 (REPEL-CV), 2.5, or 3.0] were efficacious in the reduction of retrosternal adhesions to the epicardium.
The effect of fibrin glue on inhibition of pericardial adhesions was tested using 26 beagle dogs. Dacron patches were sutured to the heart and tincture of iodine was applied to promote adhesions. Fibrin glue (3 ml) was sprayed over the patches in 15 dogs (test group), and was not separated in the remaining 11 dogs (control group). All animals in the test group had minimal adhesions between the pericardium and the epicardium or patched region, and an accumulation of gelatinous material was found in the subpericardial space. Marked fibrosis and a poor demarcation of the subpericardial space were found in the control group. The adhesion score and the visibility of coronary anatomy in the test group were significantly better than in the control group. The tension strength in the test group was significantly less than in the control group. We concluded, therefore, that fibrin glue may also be useful as an adhesion inhibitor.
Two patients were referred to our hospital with constrictive pericarditis approximately 1 year after undergoing mitral valve repair at another institution. Both repairs had included the use of a pericardial substitute, Marlex mesh, to prevent adhesion and to facilitate possible reoperations. Computed tomography and cardiac catheterization were used to establish the diagnosis of constrictive pericarditis. During surgery, dense, thickened fibrous tissue, the result of a Marlex mesh-related reaction, was found tightly adhered to the epicardium in each of the patients. It appeared that the Marlex mesh, which had been inserted to facilitate reoperation, had contributed to the development of constrictive pericarditis.
Glutaraldehyde fixed patch grafts of bovine pericardium were implanted in myocardial windows in young (3-4 months old) sheep. The samples were retrieved after one to three weeks for study with scanning electron microscopy (SEM) and energy dispersive x-ray microanalysis (EDX). A layer of porous material (pseudoneointima, PNI), consisting mostly of a dense mesh of fibers interspersed with blood cells, was noted to form on the blood contacting surface of the graft. Four distinct sets of mineralization were noted in the retrieved grafts: (1) at the blood contacting surface of the PNI; (2) within the PNI at the junction between layers of PNI with differing densities; (3) near the junction of PNI and pericardium (but in the PNI); and (4) within the pericardium. In both the PNI and pericardium the mineral was shown by EDX analysis to contain both calcium and phosphorous indicating the mineral to be a calcium phosphate. Mineralization in the PNI differed from that in the pericardium; in the PNI it was deposited in discrete regions and apparently in association with thrombi while in the pericardium it was distributed diffusely within the collagen matrix, which may influence its formation.
Operations through a previous sternotomy incision are associated with significant hazards, including cardiac injury, excessive hemorrhage during and after cardiopulmonary bypass, and postoperative sternal instability. A technique for safely opening previous sternotomy incisions has been developed at New York University Medical Center which has proved satisfactory in over 150 patients. It has been demonstrated repeatedly to be free of the serious and often lethal intraoperative and postoperative complications previously associated with this procedure.
Patches of glutaraldehyde-preserved porcine pericardium were transplanted orthotopically into 20 dogs to see if they might make a satisfactory pericardial substitute. Two dogs had mediastinal infections and were excluded from this study. All animals were reoperated on at regular intervals between 15 and 300 days. In 15 dogs there were no adhesions between the porcine pericardium and the host's epicardium. Histological study showed healing between both pericardiums and no degenerative changes in transplanted pericardium. Glutaraldehyde porcine pericardium has been utilized in 8 patients to close the pericardial cavity. There have been no problems related to the pericardial grafts after a maximum follow-up of 9 months.
Experiences with primary closure of the pericardium in a series of 100 patients undergoing open-heart operations are described. The pericardium was kept under tension during the operation to minimize shrinkage and permit closure at the end of the procedure. In 28 patients one pleural space was opened for drainage, whereas in 72 patients intra- and extrapericardial sumps alone were used for drainage. Measurements of sump drainage revealed that most postoperative bleeding originates from outside the pericardium. There were no instances of cardiac tamponade although 19 patients lost more than 1 L. of blood after operation and 5 required reoperation for hemorrhage. Transpleural drainage tubes were shown to be ineffective and in addition were associated with a fourfold increase in postcardiotomy syndrome and a significantly greater frequency of pleural effusion and atelectasis when compared to the use of mediastinal sump drainage alone. We have concluded that closing the pericardium and using mediastinal sump drainage minimizes the risk of cardiac tamponade and allows early localization of the site of postoperative bledding. Another advantage of pericardial closure and drainage is that postoperative adhesions and postcardiotomy syndrome will be less significant. As a consequence the danger of injuring the heart in a subsequent operation is lessened.
Pericardial substitutes have been shown to decrease the formation of pericardial adhesions. For a pericardial substitute to be properly implanted, it must lie over the heart smoothly without buckling and prevent the accumulation of blood under its surface. The technique we describe prevents buckling of the pericardial substitute and consequently reduces the formation of pericardial adhesions.
This experimental study summarizes our experience with the use of a new polytetrafluoroethylene surgical membrane as a pericardial substitute in 24 dogs. Group I consists of 10 dogs who underwent simple pericardial closure with this membrane, and in Group II, 14 dogs had pericardial closure with this membrane after cardiac procedures. There were three early deaths. Two dogs that had undergone an associated right heart procedure developed endocarditis at 4 and 7 months, respectively. Postmortem examinations were performed in all 21 surviving dogs. The pericardial membranes were found to be acellular and to have maintained their initial characteristics. The epicardium was normal and the coronary arteries easily visible. Seven of the eight 0.2 mm thick membranes caused filmy pericardial adhesions. None of the 0.1 mm thick membranes formed adhesions or had any structural change. We conclude that this new 0.1 mm thick polytetrafluoroethylene surgical membrane should be clinically tested to see if it will reduce or eliminate pericardial adhesions and facilitate cardiac reoperation.
In a limited series of 87 patients, the pericardial cavity was closed with a patch of heterologous glutaraldehyde-preserved pericardium. Five specimens have become available for macroscopic and microscopic study, with a postimplant time ranging between 1.5 and 59 months. The patches maintained their initial structure, but the reaction over the epicardial area facing the graft greatly impeded the recognition of the coronary vessels.
Cardiac reoperations, particularly for coronary revascularization, are becoming more frequent and carry increased risk of damage to the heart during resternotomy. We experimentally evaluated a pericardial meshing technique to facilitate primary pericardial closure. In 18 mongrel dogs, an 8 by 5 cm pericardial flap was fashioned through a left thoracotomy. A standardized procedure for induction of pericardial adhesions was carried out in all animals. Animals were divided into three groups of six animals each: Group I (control)--the pericardial flap was primarily resutured; Group II--the flap was meshed and then resutured; and Group III--the flap was replaced by a pericardial substitute. Animals were put to death 8 weeks postoperatively and the pericardial space was examined for adhesions and epicardial reaction. The extent of adhesions and epicardial reaction was graded as: 0--none; 1--minimal; 2--moderate; and 3--severe. Both in Group I and Group III severe pericardial adhesions (grade 2-3) and epicardial reactions (grade 2-3) were formed, which obscured the underlying coronary anatomy. In Group II pericardial adhesions and epicardial reactions were none to minimal (grade 0-1) and the underlying coronary anatomy was not obscured. The meshed pericardium was completely regenerated by normal pericardium within several weeks. This study demonstrates that pericardial meshing facilitates primary tension-free pericardial closure. Free drainage of intrapericardial blood is achieved. A complete anatomic layer between heart and sternum is restored. Pericardial meshing is superior to the pericardial substitutes examined, as adhesions and epicardial reactions are significantly reduced, and the coronary anatomy is readily identifiable.
The use of commercially available Dacron patch coated with silicone rubber (Mediform dura substitute) as a partial pericardial replacement to reduce postoperative mediastinal adhesions is reported. The authors studied this patch both in the experimental animal and in the cardiac surgical patient. In the experimental animal, the material significantly reduced adhesions between the epicardial surface and the surrounding thoracic structures. The value of the patch, however, was negated by supervening infection. Clinically, five operative deaths occurred in 28 patients in whom the artificial material was partially substituted for the pericardium. In none of these was the presence of the artificial patch considered contributory. Mediastinal infection necessitated patch removal in 1 case, with full recovery. The artificial patch facilitated dissection over the cardiac surface in 1 further patient in whom mitral valve replacement was carried out 24 months after aortic valve replacement.
Processed bovine pericardium is increasingly used as a pericardial substitute. It is allegedly nonreactive with epicardium, but adequate clinical data are lacking on this subject. A case report is presented wherein a dense epicardial reaction to processed bovine pericardium was found at reoperation. Histologic examination confirmed the presence of a severe inflammatory response.
We examined the impact of mediastinal healing on right ventricular performance in three groups of five piglets by performing gated blood pool scans in two planes to determine right ventricular ejection fraction. Animals in Group I then had sternotomy and excision of anterior pericardium. Group II animals had a similar operation plus insertion of a silicone rubber sheet as a pericardial substitute. Group III animals (controls) had no operation. Each group was followed up for 60 days, after which gated blood pool scans were repeated in a manner identical to the initial study. Experimental animals in Groups I and II were then put to death and autopsied. Adhesion formation between the right ventricle and sternum was graded on a 0 to 3 scale. Group I animals showed a significant average decline in right ventricular ejection fraction of 19.2% (p less than 0.02). Group II animals demonstrated an average decrease in ejection fraction, although not significant, of 12.2%. Groups I and II combined showed a significant average loss in ejection fraction of 15.7% (p less than 0.01). Severity of adhesions between the right ventricle and sternum correlated well with loss of right ventricular ejection fraction (p less than 0.01). Group III controls demonstrated no significant change in ejection fraction. Mediastinal healing and fibrous attachment of the right ventricle to the sternum may play a significant role in loss of right ventricular ejection fraction after cardiac operations. Variability in loss of right ventricular ejection fraction is related to intensity of the mediastinal healing process.
The development of postoperative pericardial adhesions increases the risk of cardiac reoperations because of the danger of damaging the heart, great vessels, or grafts. Several pericardial substitutes have been tested in the past in an attempt to facilitate reoperation, with inconclusive results. This study evaluated eight different materials as pericardial substitutes: six synthetic materials and two different preparations of bovine pericardium. In 32 dogs a 10 by 5 cm piece of pericardium was excised through a right thoracotomy and the defect closed with a measured patch. Each material tested was implanted in four dogs that were put to death at 3, 6, 9, and 12 months. At autopsy the development of adhesions and epicardial reaction were graded as none, minimal, moderate, and severe. Histologic studies of the patch, the epicardium, and the suture line were performed. Our results suggest that both types of bovine pericardium were an excellent substitute. Although minimal adhesions developed, these were easily dissected. The underlying anatomy was clearly recognizable because of the lack of epicardial reaction. Silicone rubber-coated polyester fabric was an acceptable material for the prevention of adhesions, but a severe fibrous epicardial reaction impeded the recognition of the coronary arteries. Both silicone-filled and high-porosity polytetrafluoroethylene (PTFE) films reduced adhesions but caused a severe epicardial reaction. The other synthetic materials were considered inferior because of severe epicardial reaction and/or structural deterioration.
Reoperations following cardiac procedures have an increased risk because of the danger of damaging the heart, great vessels, or grafts because of adhesions to the sternum and anterior chest wall. We report our experience with the use of silicone rubber as a pericardial substitute in 102 patients--58 children undergoing palliative and corrective operations and 44 adults undergoing porcine valve insertion or coronary revascularization. The pericardial substitute was used only in cases in which reoperation was considered likely. There were no mediastinal infections. One adult had signs of cardiac constriction which improved markedly on administration of anti-inflammatory agents. Seven patients required reoperation for bleeding. Two patients who underwent Fontan procedures developed pericardial effusions necessitating a pericardial window. Reoperation was undertaken 1 to 12 months postoperatively in seven patients, all of whom were children. The silicon rubber greatly facilitated opening of the chest bone but did not affect the formation of adhesions within the pericardium. Postmortem examinations have been obtained in two cases 5 and 9 months postoperatively, and showed a thin layer of dense fibrous tissue adjacent to the silicone rubber. We conclude that silicone rubber may be used as a pericardial substitute and that it facilitates reoperation following cardiac operations. Particular caution should be used in patients undergoing Fontan procedures, as there appears to be a tendency for pericardial effusions and tamponade to develop.
Complete closure of the pericardial sac after open-heart surgery is thought to be a help in avoiding some postoperative complications and in facilitating reoperation. Since 1977, sixty-six patients who were subjected to open-heart surgery had glutaraldehyde stabilized xenogeneic bovine pericardial patches inserted to achieve closure of their own pericardial sacs. There were no hemodynamic problems related to the implantation of these patches. All 60 surviving patients were clinically well during a follow-up of 145 patient-years. Reoperation was undertaken in three patients 2(1/2), 3, and 7 years after the initial operation. The presence of the pericardial patch greatly facilitated the reopening of the chest because it prevented the formation of adhesions between the patch and the epicardium. Histologically, the implanted pericardium consisted of laminae of collagen fibrils containing evenly dispersed fibrocyte nuclei and parallel runs of fairly wide, separated elastic fibrils. There was no evidence of immune reaction. On the basis of our findings that there was no host reaction or complications after its use, glutaraldehyde stabilized xenogeneic bovine pericardium appears to be the material of choice for patch closure of the pericardium when primary closure alone is not feasible.
Protection of the heart during reoperation using a bovine pericardial shield: clinical experience
- Dietzman
Clinical application of a new material, “expanded polytetrafluoroethylene.”
- Sakamoto