[show abstract][hide abstract] ABSTRACT: BACKGROUND: Despite continuous improvements in materials and perfusion techniques, cardiac surgery still causes lung injury and a delay of pulmonary recovery. Currently, there is no gold standard for quantifying cardiac surgery induced lung injury and dysfunction. Adding objective measures, such as plasma biomarkers, could be of great use here. In this study the utility of lung epithelium specific proteins as biomarkers for lung dysfunction was evaluated. METHODS: Serial measurements of plasma concentrations of Clara cell 16 kD (CC16) protein, Surfactant protein D (SP-D), Elastase and Myeloperoxidase were performed on blood samples from 40 patients who underwent coronary artery bypass grafting with cardiopulmonary bypass (CABG, n = 20) or without cardiopulmonary bypass (OPCAB, n = 20). RESULTS: The increase of SP-D and CC16 between pre-operative concentrations and concentrations at the end of cardiopulmonary bypass, correlated with the Aa-O2 gradient at 1 hour on the ICU (Rs = 0.409, p = .016 and Rs = 0.343, p = .043, respectively).Furthermore, SP-D and CC16 were higher in CABG than in OPCAB at the end of surgery [8.96 vs. 4.91 ng/mL, p = .042 and 92 vs. 113%, p = .007, respectively]. After 24 h both biomarkers returned to their baseline values. CONCLUSIONS: Our results show that increases in plasma of SP-D and CC16 correlate with clinical lung injury after coronary artery bypass surgery. Therefore, lung epithelium specific proteins seem to be a useful biomarker for measuring lung injury in the setting of cardiac surgery.
Journal of Cardiothoracic Surgery 01/2013; 8(1):4. · 0.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: A minimized perfusion circuit (MPC) has proven to be superior to the conventional circulatory perfusion bypass (CCPB) as it reduces the blood-material interaction and hemodilution. Until now not much is known about impact these different perfusion systems have on the brain. The objective of this study is to determine carnosinase and brain-type fatty binding protein (BFABP) activity as novel specific biomarkers for ischemic brain tissue damage and how their activity differs during and after MPC and CCPB as well as to compare the inflammatory response of both perfusion systems. In a prospective pilot study, 28 patients undergoing coronary artery bypass grafting were randomly divided into an MPC group (n = 14) and a CCPB group (n = 14). Blood samples were taken before, during, and after operation until the fifth postoperative day. The brain biomarker carnosinase was determined by measuring the rate of histidine production from the substrate homocarnosine, whereas BFABP and interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) and endothelin-1 were determined by enzyme immunoassay. The mean serum carnosinase activity was significantly higher in MPC (0.57 ± 0.34 nM histidine/mL/min) as compared with the CCPB group (0.36 ± 0.13 nM histidine/mL/min) at the end of operation (P = 0.02). The BFABP did not show any difference between the two groups in the immediate postoperative period until the second postoperative day. From that time point onward, it showed a steep increase in the CCPB group (581.3 ± 157.11 pg/mL) as compared with the concentrations in the MPC group (384.6 ± 39 pg/mL) (P = 0.04). The inflammation markers interleukin-6 and CRP showed a similar pattern in both groups without significant difference. In contrast, the leukocyte count on operation day and endothelin-1 on the first postoperative day were significantly higher in the CCPB group (P = 0.01, P = 0.03, respectively). MPC showed a significant higher and stable serum carnosinase activity during extracorporeal circulation as compared with the CCPB due to less hemodilution and a better preserved oxygen capacity. As a consequence, the antioxidant stress during MPC is limited as compared with CCPB, which means less brain tissue damage reflected by a lower BFABP release. Except endothelin-1 and leukocyte count, the inflammatory response of the MPC and CCPB was equal.
[show abstract][hide abstract] ABSTRACT: Polycaprolactone (PCL) polyester and segmented aliphatic polyester urethanes based on PCL soft segment have been thoroughly investigated as biodegradable scaffolds for tissue engineering. Although proven beneficial as long term implants, these materials degrade very slowly and are therefore not suitable in applications in which scaffold support is needed for a shorter time. A recently developed class of polyacylurethanes (PAUs) is expected to fulfill such requirements. Our aim was to assess in vitro the degradation of PAUs and evaluate their suitability as temporary scaffold materials to support soft tissue repair. With both a mass loss of 2.5-3.0% and a decrease in molar mass of approx. 35% over a period of 80 days, PAUs were shown to degrade via both bulk and surface erosion mechanisms. Fourier Transform Infra Red (FTIR) spectroscopy was successfully applied to study the extent of PAUs microphase separation during in vitro degradation. The microphase separated morphology of PAU1000 (molar mass of the oligocaprolactone soft segment = 1000 g/mol) provided this polymer with mechano-physical characteristics that would render it a suitable material for constructs and devices. PAU1000 exhibited excellent haemocompatibility in vitro. In addition, PAU1000 supported both adhesion and proliferation of vascular endothelial cells and this could be further enhanced by pre-coating of PAU1000 with fibronectin (Fn). The contact angle of PAU1000 decreased both with in vitro degradation and by incubation in biological fluids. In endothelial cell culture medium the contact angle reached 60 degrees, which is optimal for cell adhesion. Taken together, these results support the application of PAU1000 in the field of soft tissue repair as a temporary degradable scaffold.
[show abstract][hide abstract] ABSTRACT: Although the centrifugal pump has been widely used as a nonpulsatile pump for cardiopulmonary bypass (CPB), little is known about its performance as a pulsatile pump for CPB, especially on its efficacy in producing hemodynamic energy and its clinical effectiveness. We performed a study to evaluate whether the Rotaflow centrifugal pump produces effective pulsatile flow during CPB and whether the pulsatile flow in this setting is clinically effective in adult patients undergoing cardiac surgery. Thirty-two patients undergoing CPB for elective coronary artery bypass grafting were randomly allocated to a pulsatile perfusion group (n = 16) or a nonpulsatile perfusion group (n = 16). All patients were perfused with the Rotaflow centrifugal pump. In the pulsatile group, the centrifugal pump was adjusted to the pulsatile mode (60 cycles/min) during aortic cross-clamping, whereas in the nonpulsatile group, the pump was kept in its nonpulsatile mode during the same period of time. Compared with the nonpulsatile group, the pulsatile group had a higher pulse pressure (P < 0.01) and a fraction higher energy equivalent pressure (EEP, P = 0.058). The net gain of pulsatile flow, represented by the surplus hemodynamic energy (SHE), was found much higher in the CPB circuit than in patients (P < 0.01). Clinically, there was no difference between the pulsatile and nonpulsatile groups with regard to postoperative acute kidney injury, endothelial activation, or inflammatory response. Postoperative organ function and the duration of hospital stay were similar in the two patient groups. In conclusion, pulsatile CPB with the Rotaflow centrifugal pump is associated with a small gain of EEP and SHE, which does not seem to be clinically effective in adult cardiac surgical patients.
[show abstract][hide abstract] ABSTRACT: In transfusion medicine, frozen red blood cells (RBCs) are an alternative for liquid-stored RBCs. Little is known about the rheologic properties (i.e., aggregability and deformability) of thawed RBCs. In this study the rheologic properties of high-glycerol frozen RBCs and postthaw stored in saline-adenine-glucose-mannitol medium were compared to those of conventionally liquid-stored and fresh RBCs.
Fresh RBCs were obtained from healthy volunteers. Leukoreduced liquid-stored and thawed deglycerolized RBC units were obtained from the Sanquin Blood Bank. RBCs were tested for aggregability (aggregation index [AI]), deformability (elongation index [EI]), and various hematologic variables.
The AI of thawed RBCs was reduced, compared to fresh and liquid-stored RBCs (p<0.05). The EI of stored RBCs was significantly enhanced over a shear stress range of 2.0 to 50Pa compared to fresh RBCs (p<0.05). No significant differences in EI between thawed and 21- or 35-day liquid-stored RBCs were observed. The osmotic fragility, hemolysis, mean cell volume, and mean cell hemoglobin concentration of thawed RBCs were markedly altered, compared to fresh and liquid-stored RBCs (p< 0.05). The adenosine triphosphate (ATP) content of thawed RBCs was similar to 3- or 21-day liquid-stored and fresh RBCs.
Thawed RBCs are more fragile than conventionally liquid-stored and fresh RBC. The freeze-thaw-wash process, however, did not adversely affect the aggregability and deformability or the ATP content of thawed RBCs. Based on the rheologic properties, cryopreserved RBCs are a valuable alternative to liquid-stored RBCs.
[show abstract][hide abstract] ABSTRACT: To investigate the effect of benfotiamine on urinary albumin excretion (UAE) and the tubular damage marker kidney injury molecule-1 (KIM-1) in patients with type 2 diabetes and nephropathy.
Patients with type 2 diabetes and UAE equivalent to 15-300 mg/24 h, despite ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs), were randomly assigned to 12 weeks of benfotiamine (900 mg/day) (n = 39) or placebo (n = 43).
Compared with placebo, benfotiamine treatment resulted in significant improvement of thiamine status (P < 0.001). Benfotiamine treatment did not significantly decrease 24-h UAE or 24-h KIM-1 excretion.
In patients with type 2 diabetes and nephropathy, high-dose benfotiamine treatment for 12 weeks in addition to ACE-Is or ARBs did not reduce UAE or KIM-1 excretion, despite improvement of thiamine status.
Diabetes care 04/2010; 33(7):1598-601. · 7.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Red blood cell (RBC) units stored for more than 2 weeks at 4 degrees C are currently considered of impaired quality. This opinion has primarily been based on altered RBC rheologic properties (i.e., enhanced aggregability, reduced deformability, and elevated endothelial cell interaction), during prolonged storage of nonleukoreduced RBC units. In this study, the rheologic properties and cell variables of leukoreduced RBC units, during routine blood bank storage in saline-adenine-glucose-mannitol, were investigated.
Ten leukoreduced RBC units were stored at the blood bank for 7 weeks at 4 degrees C. RBCs were tested weekly for aggregability, deformability, and other relevant variables.
RBC aggregability was significantly reduced after the first week of storage but recovered during the following weeks. After 7 weeks aggregability was slightly, but significantly, reduced (46.9 + or - 2.4-44.3 + or - 2.2 aggregation index). During storage the osmotic fragility was not significantly enhanced (0.47 + or - 0.01% phosphate-buffered saline) and the deformability at shear stress of 3.9 Pa was not significantly reduced (0.36 + or - 0.01 elongation index [EI]). The deformability at 50 Pa was reduced (0.58 + or - 0.01-0.54 + or - 0.01 EI) but remained within reference values (0.53 + or - 0.04). During 5 weeks of storage, adenosine triphosphate was reduced by 54% whereas mean cell volume, pH, and mean cell hemoglobin concentration were minimally affected.
RBC biochemical and physical alterations during storage minimally affected the RBC ability to aggregate and deform, even after prolonged storage. The rheologic properties of leukoreduced RBC units were well preserved during 7 weeks of routine blood bank storage.
[show abstract][hide abstract] ABSTRACT: Hemodilution is the main cause of a low hematocrit concentration during cardiopulmonary bypass. This low hematocrit may be insufficient for optimal tissue oxygen delivery and often results in packed cell transfusion. Our objective in this study was to find a relationship between intraoperative hematocrit and allogeneic blood transfusion on release of postoperative injury markers from the kidneys and the splanchnic area.
Fifty consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass were included. Systemic tissue hypoxia was assessed by lactate concentrations. Kidney and splanchnic ischemia were assessed by the measurement of N-acetyl-beta-D-glucosaminidase (NAG) and intestinal fatty acid binding protein (IFABP) in urine. Patients were retrospectively placed into groups according to their lowest hematocrit concentration on bypass (<24% or >or=24%).
The intraoperative lactate and the postoperative NAG and IFABP concentrations were higher in the low hematocrit group (<24%) than in the high hematocrit group (>or=24%; P < 0.05). Low hematocrit correlated with higher lactate concentrations (R(2) = 0.150, P < 0.01) and with higher NAG concentrations (R(2) = 0.138, P < 0.01) and IFABP concentrations (R(2) = 0.107, P < 0.01) postoperatively. Transfusion of packed cells during cardiopulmonary bypass correlated with higher lactate (R(2) = 0.089, P < 0.05), NAG (R(2) = 0.431, P < 0.01), and IFABP concentrations (R(2) = 0.189, P < 0.01).
The results support the concept that hemodilution below an intraoperative hematocrit of 24% and consequently transfusion of red blood cells is related to release of injury markers of the kidneys and splanchnic area.
Anesthesia and analgesia 08/2009; 109(2):331-9. · 3.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Leucocyte filtration of salvaged blood has been suggested to prevent patients from receiving activated leucocytes during auto-transfusion in cardiac surgery. This study examines whether leucocyte filtration of salvaged blood affects the red blood cell (RBC) function and whether there is a difference between filtration of the concentrated and diluted blood on RBC function.
Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly divided into a group receiving leucocyte filtration of concentrated blood (High-Hct, n=20) and another group receiving leucocyte filtration of the diluted blood (Low-Hct, n=20). During operation, all the salvaged blood, as well as the residual blood, from the heart-lung machine was filtered. In the High-Hct group, blood was concentrated with a cell saver prior to filtration, whereas in the Low-Hct group, blood was filtered without concentration. RBC function was represented by RBC aggregation and deformability measured by a laser-assisted optical rotational cell analyser and by the RBC 2,3-diphosphoglycerate (2,3-DPG) and adenosine triphosphate (ATP) contents with conventional biochemical tests.
Leucocyte filtration of diluted blood with a low haematocrit (14+/-4%) did not affect RBC function. However, when the concentrated blood with a high haematocrit (69+/-12%) was filtered, there was a reduction of ATP content in RBCs after passing through the filter (from 1.45+/-0.57 micromol g(-1) Hb to 0.92+/-0.75 micromol g(-1) Hb, p<0.05). For patients who received the concentrated blood, their in vivo RBC function did not differ from those who received diluted blood.
Leucocyte filtration of the diluted salvaged blood during cardiac surgery does not affect RBC function, but it tends to deplete the ATP content of RBCs as the salvaged blood has been concentrated prior to filtration.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 07/2009; 36(5):877-82. · 2.40 Impact Factor
[show abstract][hide abstract] ABSTRACT: Hemolysis testing is the most common method to determine the hemocompatibility properties of biomaterials. There is however no consensus on the procedures of hemolysis testing due to insufficient comparative studies on the quality of the red blood cells used and the experimental conditions of testing. In this study we determined the effects of a number of incubation variables on the sensitivity and reproducibility of the hemolysis test using positively as well as negatively responding biomaterials and compared these results to those obtained according to the American Society for Testing and Materials (ASTM) standard. The ASTM standard method recommends hemolysis testing with highly diluted rabbit blood that is static incubated for 3 h. In this study we found that 24 h incubation of a biomaterial sample at 37 °C in slightly diluted human blood or with washed red blood cells was the most sensitive hemolysis test. Moreover usage of cryopreserved human RBC in the hemolysis test seemed to be a good alternative for fresh RBC since cryopreserved and fresh human RBC gave similar results in the hemolysis test. Hemolysis testing by exposing diluted rabbit erythrocytes to biomaterials as according to the ASTM method or by exposing biomaterials extract in saline to washed human red blood cells gave a different outcome and appeared not to be representative for clinical applications.
Materials Science and Engineering: C. 01/2009; 29(5):1650-1654.
[show abstract][hide abstract] ABSTRACT: Mechanical cell salvage is increasingly used during cardiac surgery. Although this procedure is considered safe, it is unknown whether it affects the red blood cell (RBC) function, especially the RBC aggregation, deformability, and the contents of 2,3-diphosphoglycerate (2,3-DPG). This study examines the following: (1) whether the cell salvage procedure influences RBC function; and (2) whether retransfusion of the salvaged blood affects RBC function in patients.
Forty patients undergoing cardiac surgery with cardiopulmonary bypass were randomly allocated to a cell saver group (n = 20) or a control group (n = 20). In the cell saver group, the blood aspirated from the wound area and the residual blood from the heart-lung machine were processed with a continuous-flow cell saver before retransfusion. In the control group this blood was retransfused without processing. The RBC aggregation and deformability were measured with a laser-assisted optical rotational cell analyzer and 2,3,-DPG by conventional laboratory test.
The cell saver procedure did not influence the RBC aggregation but significantly reduced the RBC deformability (p = 0.007) and the content of RBC 2,3-DPG (p = 0.032). However, in patients receiving the processed blood, their intraoperative and postoperative RBC aggregation, deformability, and 2,3-DPG content did not differ from those of the control patients. Both groups of patients had a postoperative drop of RBC function as a result of hemodilution.
The mechanical cell salvage procedure reduces the RBC deformability and the cell 2,3-DPG content. Retransfusion of the processed blood by cell saver does not further compromise the RBC function in patients undergoing cardiac surgery with cardiopulmonary bypass.
The Annals of thoracic surgery 12/2008; 86(5):1570-5. · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Intra-operative cell salvage is increasingly used, especially in longer cases with continuing blood loss. However it is unknown if the quality of processed blood is affected when larger quantities of blood are processed. We hypothesized that the quality of the washed blood decreases after multiple runs.
Intra-operative cell salvage was performed in 42 consecutive patients undergoing cardiac surgery. When 1250 ml of blood was collected in the blood collection reservoir, this was processed and returned to the patient. In 21 patients more than 2500 ml of blood was collected during the whole procedure, thus allowing at least two subsequent runs with the auto-transfusion device. Blood samples were drawn from the blood collection reservoir of the cell saver device before, and from the processed blood after each run.
After the first run interleukin-6 concentrations were reduced with 85% (from 21+/-35 microg/l to 3.1+/-4.4 microg/l), whereas after the second run 72% was removed (63+/-69 microg/l to 17.6+/-25.3 microg/l). Leukocyte counts almost doubled after both processing runs (from 2.6+/-1.5 x 10(9)/l to 5+/-3.6 x 10(9)/l) and from 3.9+/-2.2 x 10(9)/l to 7.7+/-5.9 x 10(9)/l), hemoglobin concentration (14.8+/-1.6 mmol/l vs 15.0+/-1.1 mmol/l), free hemoglobin (2.3+/-1.6g/l vs 2.1+/-1.4 g/l) and platelet counts (18+/-9 x 10(9)/l vs 28+/-23 x 10(9)/l) were not different between the two runs.
Our results suggest, based on interleukin-6 and free hemoglobin washout that the quality of the processed blood remains constant with multiple runs of the cell saver device.
European Journal of Cardio-Thoracic Surgery 09/2008; 34(2):350-3. · 2.67 Impact Factor
[show abstract][hide abstract] ABSTRACT: Transient, subclinical myocardial, renal, intestinal, and hepatic tissue injury and impaired homeostasis is detectable even in low-risk patients undergoing conventional cardiopulmonary bypass (CPB). Small extracorporeal closed circuits with low priming volumes and optimized perfusion have been developed to reduce deleterious effects of CPB.
A prospective, randomized trial was conducted in 49 patients undergoing elective coronary artery bypass graft surgery either with the use of a standard or mini-CPB system (Synergy). We determined early postoperative inflammatory response (leukocytosis, C-reactive protein, urine interleukin-6), platelet consumption and activation (urine thromboxane B2), proximal renal tubular injury (urine N-acetyl-glucosaminidase), and intestinal injury (intestinal fatty acid binding protein).
In patients undergoing coronary artery bypass grafting with a mini-CPB system, we observed decreased priming volumes with subsequent attenuation of on-pump hemodilution, improved hemostatic status with reduced platelet consumption and platelet activation, decreased postoperative bleeding and minimized transfusion requirements. We also found reduced leukocytosis and decreased urinary interleukin-6. Levels of urine N-acetyl-glucosaminidase were on average threefold lower, and urinary intestinal fatty acid binding protein was 40% decreased in the patients on the mini-CPB system, as compared with standard CPB.
The use of the mini-CPB system during myocardial revascularization represents a viable nonpharmacologic strategy that can attenuate the alterations in the hemostatic system, reduce bleeding and transfusion requirements, decrease systemic inflammatory response, and reduce immediate postoperative renal and intestinal tissue injury.
The Annals of thoracic surgery 06/2007; 83(5):1760-6. · 3.74 Impact Factor
[show abstract][hide abstract] ABSTRACT: Activated leukocytes and fat particles are associated with organ injury after a cardiac surgery. Filters are currently used to remove either leukocytes or fat particles. A novel approach with a filter that combines leukocyte and fat removal might be clinically useful. As it is not known which type of filter has a good and safe performance in both leukocyte and fat removal, we measured in this study the leukocyte and fat removal properties and the biocompatibility of three different filters. We used six Pall RS1 (Pall, Portsmouth, England) leukocyte removal filters, six Pall LipiGuard fat removal filters, and six Fresenius Biofil 02 (Fresenius, Emmer-Compascuum, The Netherlands) leukocyte removal filters and measured the passage times of 500 and 1000 mL of residual heart-lung machine blood. We determined the circulating leukocyte and platelet counts, and total hemoglobin, triglyceride, and free fatty acid concentration after the filters. In addition, we measured free hemoglobin, plasma elastase (Merck, Darmstadt, Germany), and complement C5-9 (Quidel, San Diego, CA, U.S.A.) to assess the biocompatibility of the filters. The circulating fat particles were calculated with an automated hematology analyzer. The passage time for the blood was shortest for the Biofil filter (P = 0.02, analysis of variance). The total leukocyte counts (P = 0.04) and fat particles (P = 0.02) were higher after the LipiGuard filter. This filter also had a higher increase in free hemoglobin concentration (P = 0.03). We conclude that the leukocyte removal filters were superior to the fat removal filter both in leukocyte and fat removal.
[show abstract][hide abstract] ABSTRACT: The Trillium coating is designed to minimize adsorption of protein and the attachment of cells and other particles. The present study was undertaken to investigate the effect of surface coating on the adhesion of thrombotic components (activated platelets, white blood cells and fibrin) to the surface of a clinically used oxygenator. Twenty patients undergoing elective coronary artery bypass grafting (CABG) were randomized to one of the two oxygenator groups: non-coated (NC, n = 10) or Trillium-coated (TC, n = 10). Platelet and white blood cell counts and factor XIIa concentrations were determined prior to the induction of anesthesia and at the end of cardiopulmonary bypass (CPB). Binding of activated platelets, white blood cells and fibrin to the artificial surfaces was quantified by means of antibody binding and histological validation was achieved by scanning electron microscopy. Patient demographic and CPB data were similar for the two groups. No significant differences between the groups were found for any of the tested thrombotic components. However, observations from our scanning electron microscopy suggested a release of formed particles from the Trillium-coated surface. Primary adhesion of activated platelets, white blood cells and fibrin to the artificial surface of the venous blood inlet from an oxygenator is not affected by the Trillium surface coating under conditions of full systemic heparinization.