[Show abstract][Hide abstract] ABSTRACT: LVAD speed adjustment according to a functioning aortic valve has hypothetic advantages but could lead to submaximal support. The consequences of an open aortic valve policy on exercise capacity and hemodynamics have not yet been investigated systematically.
Journal of Cardiothoracic Surgery 05/2014; 9(1):93. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Veno-venous extracorporeal membrane oxygenation (vvECMO) can be a life-saving therapy in patients with severe acute lung failure refractory to conventional therapy. Nevertheless, vvECMO is a procedure associated with high costs and resource utilization. The aim of this study was to assess published models for prediction of mortality following vvECMO and optimize an alternative model.
Established mortality risk scores were validated to assess their usefulness in 304 adult patients undergoing vvECMO for refractory lung failure at the University Medical Center Regensburg from 2008 to 2013. A parsimonious prediction model was developed based on variables available before ECMO initiation using logistic regression modelling. We then assessed whether addition of variables available one day after ECMO implementation enhanced mortality prediction. Models were internally validated and calibrated by bootstrapping (400 runs). Predictive ability, goodness-of-fit and model discrimination were compared across the different models.
In the present study population, existing mortality prediction tools for vvECMO patients showed suboptimal performance. Evaluated before vvECMO initiation, a logistic prediction model comprising age, immunocompromised state, artificial minute ventilation, pre-ECMO serum lactate and haemoglobin concentrations showed best mortality prediction in our patients (area under curve, AUC: 0.75). Additional information about norepinephrine dosage, fraction of inspired oxygen, C-reactive protein and fibrinogen concentrations the first day following ECMO initiation further improved discrimination (AUC: 0.79, P = 0.03) and predictive ability (likelihood ratio test, P < 0.001). When classifying patients as lower (<40%) or higher (>80%) risk based on their predicted mortality, the pre-ECMO and day1-on-ECMO models had negative/positive predictive values of 76%/82% and 82%/81%, respectively.
While pre-ECMO mortality prediction remains a challenge due to large patient heterogeneity, evaluation one day after ECMO initiation may improve the ability to separate lower- and higher-risk patients. Our findings support the clinical perception that chronic health condition, high comorbidity and reduced functional reserves are strongly related to survival during and following ECMO support. Renewed evaluation the first day after ECMO initiation may provide enhanced guidance for further handling of ECMO patients. Despite the usefulness of prediction models, thorough clinical evaluation should always represent the cornerstone in decision for ECMO.
Critical care (London, England) 04/2014; 18(2):R67. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Postoperative Acute Kidney Injury (AKI) after coronary artery bypass grafting (CABG) is a common complication associated with significant morbidity and mortality. Cardiopulmonary bypass (CPB) is accepted to contribute to the occurrence of AKI and is of particular importance as it can be avoided by using the off-pump technique. However the renoprotective properties of off-pump (CABG) are controversial. This analysis evaluates the impact of cardiopulmonary bypass on renal function.
A matched-pair analysis of 1428 patients undergoing coronary artery bypass grafting was conducted. The patients were stratified according to their preoperative renal function and to risk factors for postoperative AKI. The development of the glomerular filtration rate (GFR) from before surgery until hospital discharge was analyzed. Incidence of AKI were analyzed. Furthermore the impact of CPB duration on postoperative GFR was assessed.
The occurrence of AKI increases the risk of thirty-day mortality (odds ratio of 4.3). The postoperative GFR decreases significantly after coronary artery bypass grafting but does not differ between onpump and offpump CABG (60.2 +/- 24.5 vs 60.7 +/- 24.8; p = 0.54). No difference regarding the incidence (26.6% vs 25%) and severity of AKI between cardiopulmonary bypass and the off-pump technique could be found. Duration of cardiopulmonary bypass does not correlate with the decline in postoperative glomerular filtration rate (Pearson Product Moment Correlation; p > 0.050).
Neither the mere use nor duration of cardiopulmonary bypass proofed to be a risk factor for developing postoperative AKI in CABG patients with a comparable preoperative risk profile for postoperative renal dysfunction. Furthermore, the severity of postoperative AKI is not affected by the use of cardiopulmonary bypass.
Journal of Cardiothoracic Surgery 01/2014; 9(1):20. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Early markers of oxygenator dysfunction during prolonged use of extracorporeal membrane oxygenation (ECMO) are important for timely exchange to avoid sudden loss of function due to clot formation within the system. The measurement of d-dimers (DDs) in plasma might be a marker for early diagnosis of thrombus formation and dysfunction of heparin-coated membrane oxygenators (MOs).
This is a retrospective study on prospectively collected data of 24 adult acute respiratory distress syndrome patients requiring long-term veno-venous ECMO with at least 1 MO exchange. Kinetics of coagulation, inflammation, and oxygenator function were analyzed before and after MO exchange.
Median (interquartile range) support duration is 20 (15-29) days. Thirty-four MOs had to be replaced. Exchange occurred due to visible thrombus formation in the MO (n = 16), worsening gas exchange (n = 11), increased blood flow resistance (n = 1), and activation of coagulation with diffuse bleeding (n = 6). In 15 cases, DDs were continuously elevated and, therefore, not suitable as marker for MO exchange. In the remaining 19 cases, DDs increased significantly within 3 days before exchange from 15 (9-20) to 30 (21-35) mg/dL (P = .002) and declined significantly within 1 day thereafter to 13 (7-17) mg/dL (P = .003).
An increase in plasma DD concentration in absence of other explaining pathology can be helpful in predicting an MO exchange in miniaturized heparin-coated ECMO systems.
Journal of critical care 12/2013; · 2.13 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Membrane oxygenator (MO) failure is a known hazard during venovenous extracorporeal membrane oxygenation (v-v ECMO) therapy. Knowledge about technical and performance details of different ECMO systems (Maquet, Rastatt, Germany; Medos, Stolberg, Germany; Sorin, Modena, Italy) licensed for adults with acute lung failure might improve their handling. This retrospective study comprises 186 adult patients (Regensburg ECMO Registry) treated with v-v ECMO. Flow dynamic data were used to analyze the performance of different blood pumps, cannula types, and MOs to maintain an adequate blood flow (1-5 L/min). Usage of the Medos ECMO system in critically ill patients required a higher pump speed and generated a higher pressure drop across the MO (dpMO), however, without an increase in free plasma hemoglobin. The dpMO depended on the type of MO and increased with blood flow as expected. Type-specific normal values are reported. A distinct increase in dpMO above normal values within 1 day required an immediate MO exchange. This was an infrequent technical complication (3%). Finally, pressure-flow performance of single dual-lumen cannulas (27 Fr) was comparable with small single-lumen cannulas (15 Fr), without an increased risk of technical-induced hemolysis. Despite different performances, all current commercially available adult v-v ECMO systems produce adequate blood flow without an increased risk in technical-induced hemolysis. Familiarity with the specific properties of individual systems allows early detection of technical complications. Additionally, the choice of an adequate cannula requires a closer consideration of the individual patient situation.
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal life support (ECLS) is a rescue option in critically ill patients. Since fast available and appropriate for respiratory and circulatory failure, it is frequently applied in resuscitation scenarios. Neurological injury is a complication common in ECLS patients limiting outcome, particularly after resuscitation. In this study, the institutional ECLS database was used to correlate neuron-specific enolase (NSE) serum peak values with outcome of patients supported with venoarterial (VA) ECLS during cardiopulmonary resuscitation (CPR).
From January 2011 to August 2012, 31 patients were provided with a VA ECLS during CPR (external cardiac massage). Serum NSE peaks were monitored and correlated with neurological outcome and hospital mortality. Patients were divided into two groups with mild-to-moderate and high NSE levels (cut-off value 100 μg/l).
High NSE levels were seen in 7 patients (mean 218 ± 155 μg/l) and mild-to-moderate levels in 24 patients (50 ± 23 μg/l, P = 0.0001). Duration of extracoporeal support was comparable in both groups (6.3 ± 7.5 vs 5.0 ± 4.5 days, P = n.s.). Patients with mild-to-moderate NSE levels were significantly older than those with high NSE levels (58 ± 16 vs 44 ± 15 years, P = 0.02). Six patients with high NSE levels (86%) developed severe neurological complications. Though 4 patients could be weaned from extracorporeal support, hospital mortality was 86% (6 patients). In contrast, patients with mild-to-moderate NSE levels had a hospital mortality of 46% (11 patients). Eighteen patients (75%) could be weaned from the device, and incidence of major neurological events was 29% (6 patients) only. Serum pH and lactate levels before ECLS implantation were significantly lower in patients with mild-to-moderate NSE values (pH: 7.23 ± 0.04 vs 6.93 ± 0.12, P = 0.039; lactate: 106 ± 11 vs 161 ± 16 mg/l, P = 0.023).
High NSE serum levels after ECLS correspond to poor neurological outcome and considerable mortality. Therefore, early neuroimaging is reasonable for determining therapeutic strategies in patients with high NSE peaks after resuscitation and extracorporeal support.
European journal of cardio-thoracic surgery: official journal of the European Association for Cardio-thoracic Surgery 07/2013; · 2.40 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES
Based on continuous technical innovations and recent research, extracorporeal membrane oxygenation (ECMO) has become a promising tool in the treatment of patients with acute (cardio)pulmonary failure. Nevertheless, any extracorporeal technique requires a high degree of experience and knowledge, so that a restriction to specialized centres seems to be reasonable. As a consequence of this demand, the need for inter-hospital transfer of patients with severely impaired (cardio)pulmonary function is rising. Unfortunately, most of the ECMO devices used in the clinical setting are not suitable for inter-hospital transport because of their size, weight or complexity. In this article, we describe our first experiences with the airborne transport of 6 patients on a new portable, miniaturized and lightweight extracorporeal circulation system, the Medos deltastream® DP3.METHODS
Six patients suffering acute respiratory failure were taken on venovenous ECMO (DP3) out-of-centre and transferred to the University Medical Center Regensburg by helicopter. All cardiorespiratory-relevant parameters of the patients and the technical functioning of the device were continuously monitored and documented.RESULTSImplantation of the device and air-supported transport were performed without any technical complications. The patients were transported from a distance of 66-178 km, requiring a time of 40-120 min. With the help of the new deltastream® DP3 ECMO device, a prompt stabilization of the cardiopulmonary function could be achieved in all patients. One patient was under ongoing cardiopulmonary resuscitation by the time our ECMO team arrived at the peripheral hospital and died shortly after arrival in the central emergency ward.CONCLUSIONS
Our experience shows that the deltastream® DP3 is an absolutely reliable and safe ECMO device that could gain growing importance in the field of airborne transportation of patients on ECMO due to its unsophisticated, miniaturized and lightweight characteristics.
Interactive Cardiovascular and Thoracic Surgery 07/2013; · 1.11 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Extracorporeal membrane oxygenation (ECMO) is a very effective bridging therapy in patients with cardiogenic shock. To perform coronary angiography in these patients our group developed an unique system to get urgent vascular access with minimal additional vascular complication risk. The 6 Fr coronary catheters are introduced through a standard Y-connector, which is inserted into the arterial cannula of the ECMO-line close to the patient, the blind end of which is then equipped with a haemostatic valve (Check-Flo Performer accessory adapter, Cook Medical, USA). To the best of our knowledge, we here present the first patient, in whom this system had been used to insert an 8 Fr radiofrequency ablation catheter to treat incessant ventricular fibrillation.METHODS AND RESULTS: A 66-year-old patient had been transferred with electrical storm 5 days after an acute MI. After failed interventional and medical therapies an ECMO system had been inserted (right femoral artery cannula 15 Fr, left femoral vein cannula 21 Fr) and an electrophysiological study had been performed because of incessant ventricular fibrillation episodes, which always were induced by the same ventricular premature beat (VPB). During this first EP study over the left femoral artery the VPB could be targeted and successfully ablated. Unfortunately the VPB recovered again after some days so a second EP study had to be performed. This time the left femoral artery could not be used because of a postinterventional complication so we used the arterial cannula of the ECMO system as the access for the ablation catheter using a Y-connector. Using this way again a successful ablation procedure could be performed, after getting familiar with manipulation the ablation catheter over the ECMO cannula and with the help of different curved ablation catheters. The issue of compromising of the effective lumen of the arterial cannula by the ablation catheter`s cross sectional area could be overcome with increasing the rotational speed of the V-A ECMO.CONCLUSION: Ablation of ventricular arrhythmias using a Y-connector to insert the ablation catheter into the arterial cannula is feasible in patients with a V-A ECMO system avoiding additional arterial puncture with potentially major vascular complications in critically ill patients. Manipulation of the catheter is not as easy as using a standard sheath but can well be performed after a short habituation.
[Show abstract][Hide abstract] ABSTRACT: Cardiac tamponade is a severe complication after open heart surgery. Diagnostic imaging is challenging in postoperative patients, especially if tamponade develops with subacute symptoms. Hypothesizing that delayed tamponade after open heart surgery is not sufficiently detected by transthoracic echocardiography, in this study CT scans were used as standard reference and were compared with transthoracic echocardiography imaging in patients with suspected cardiac tamponade.
Twenty-five patients after open heart surgery were enrolled in this analysis. In case of suspected cardiac tamponade patients underwent both echocardiography and CT imaging. Using CT as standard of reference sensitivity, specificity, positive and negative predictive values of ultrasound imaging in detecting pericardial effusion/hematoma were analyzed. Clinical appearance of tamponade, need for re-intervention as well as patient outcome were monitored.
In 12 cases (44%) tamponade necessitated surgical re-intervention. Most common symptoms were deterioration of hemodynamic status and dyspnea. Sensitivity, specificity, positive and negative predictive values of echocardiography were 75%, 64%, 75%, and 64% for detecting pericardial effusion, and 33%, 83%, 50, and 71% for pericardial hematoma, respectively. In-hospital mortality of the re-intervention group was 50%.
Diagnostic accuracy of transthoracic echocardiography is limited in patients after open heart surgery. Suplemental CT imaging provides rapid diagnostic reliability in patients with delayed cardiac tamponade.
Journal of Cardiothoracic Surgery 06/2013; 8(1):158. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Severe trauma with concomitant chest injury is frequently associated with Acute Lung Failure (ALF). This report summarizes our experience with Extracorporeal Lung Support (ELS) in thoracic trauma patients treated at the University Medical Center Regensburg.
A retrospective, observational analysis of prospectively collected data (Regensburg ECMO-Registry database) on all consecutive trauma patients with acute pulmonary failure requiring ELS in a 10-year interval was performed.
Between April 2002 and April 2012, 52 patients (49 male, 3 female) with severe thoracic trauma and ALF refractory to conventional therapy required ELS. The mean age was 32 +/- 14 years (range, 16 - 72). Major traffic accident (73%) was the most common trauma followed by blast injury (17%), deep fall (8%) and blunt trauma (2%). The mean Injury Severity Score (ISS) was 58.9 +/- 10.5, mean lung injury score (LIS) was 3.3 +/- 0.6 and sequential organ failure assessment (SOFA) score was 10.5 +/- 3. Twenty six patients required pumpless extracorporeal lung assist (PECLA) and twenty six patients required veno-venous extracorporeal membrane oxygenation (vv-ECMO) for primary post-traumatic respiratory failure. Mean time to ELS support was 5.2 +/- 7.7 days (range, <24h - 38 days) and mean ELS duration was 6.9 +/- 3.6 days (range, <24h - 19 days). In 24 cases (48%) ELS implantation was performed in an external facility and cannulation was done percutaneously by Seldinger`s technique in 98% of patients. Cannula-related complications occurred in 15% of patients (PECLA 19% (n= 5); vv-ECMO 12% (n= 3)). Surgery was performed in 44 patients with 16 patients under ELS prevention. Eight patients (15%) died during ELS-support and three patients (6%) died after ELS weaning. Overall survival rate was 79% compared to proposed ISS-related mortality (59%).
Pumpless and pump-driven ELS systems are an excellent treatment option in severe thoracic trauma patients with acute lung failure and facilitate survival in an experienced trauma-center with an interdisciplinary treatment approach. We encourage the use of vv-ECMO due to reduced complication rates, better oxygenation and best short-term outcome.
Critical care (London, England) 06/2013; 17(3):R110. · 4.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The complex anatomy of the aortic annulus warrants the use of three dimensional (3D) modalities for prosthesis sizing in transcatheter aortic valve implantation (TAVI). Multislice computed tomography (MSCT) has been used for this purpose, but its use may be restricted because of contrast administration. 3D transesophageal echocardiography (3D-TEE) lacks this limitation and data on comparison with MSCT is scarce. We compared 3D-TEE with MSCT for prosthesis sizing in TAVI. METHODS: Aortic annulus diameters in the sagittal and coronal plane and annulus areas in 3D-TEE and MSCT were compared in 57 patients undergoing TAVI. Final prosthesis size was left at the operator's discretion and the agreement with 3D-TEE and MSCT was calculated. RESULTS: Sagittal diameters on 3D-TEE and MSCT correlated well (r=.754, p<.0001) and means were comparable (22.3±2.1 vs. 22.5±2.3mm; p=0.2; mean difference: -0.3mm [-3.3-2.8]). On 3D-TEE, coronal diameter and annulus area were significantly smaller (p<.0001 for both) with moderate correlation (r=0.454 and r=0.592). Interobserver variability was comparable for both modalities. TAVI was successful in all patients with no severe post-procedural insufficiency. Final prosthesis size was best predicted by sagittal annulus diameters in 84% and 79% by 3D-TEE and MSCT, respectively. Agreement between both modalities was 77%. CONCLUSIONS: Annulus diameters and areas for pre-procedural TAVI assessment by 3D-TEE are significantly smaller than MSCT with exception of sagittal diameters. Using sagittal diameters, both modalities predicted well final prosthesis size and excellent procedural results were obtained. 3D-TEE can thus be a useful alternative in patients with contraindications to MSCT.
International journal of cardiology 05/2013; · 6.18 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: OBJECTIVES: This study sought to predict the value of tumor marker carbohydrate antigen 125 (CA125) before and after transcatheter aortic valve implantation (TAVI) for all-cause death and a composite endpoint of death, admission for heart failure, myocardial infarction, and stroke (major adverse cardiac events [MACE]). BACKGROUND: Risk stratification after TAVI remains challenging. The use of biomarkers in this setting represents an unmet need. METHODS: CA125 was measured in 228 patients before and after TAVI. The association with outcomes was assessed using parametric Cox regression and joint modeling for baseline and longitudinal analyses, respectively. CA125 was evaluated as logarithm transformation and dichotomized by its median value (M1 ≤15.7 U/ml vs. M2 >15.7 U/ml). RESULTS: At a median follow-up of 183 days (interquartile range: 63 to 365) and 144 days (interquartile range: 56 to 365), 50 patients (22%) died and 75 patients (33%) experienced MACE. A 3-fold increase in the rates for death and MACE was observed in patients above the median (M2 vs. M1) of CA125 (5.2 vs. 1.6 per 10 person-years and 8.3 vs. 3.3 per 10 person-years, respectively; p for both <0.001). In a multivariable analysis adjusted for logistic EuroSCORE, New York Heart Association functional class III/IV, and device success, baseline values of CA125 (M2 vs. M1) independently predicted death (hazard ratio [HR]: 2.18; 95% confidence interval [CI]: 1.11 to 4.26; p = 0.023) and MACE (HR: 1.77; 95% CI: 1.05 to 2.98; p = 0.031). In the longitudinal analysis, lnCA125 as a time-varying exposure, was highly associated with both endpoints: HR: 1.47; 95% CI: 1.01 to 2.14; p = 0.043 and HR: 2.26; 95% CI: 1.28 to 3.98; p = 0.005, for death and MACE, respectively. CONCLUSIONS: Serum levels of CA125 before and after TAVI independently predict death and MACE.
[Show abstract][Hide abstract] ABSTRACT: This study evaluated the pharmacokinetics of tacrolimus (Tac) in a novel self-microemulsifying drug delivery system (SMEDDS) for improved oral administration. SMEDDS Tac consisted of ethyl oleate as the oily phase, Solutol HS 15 as the surfactant and glycofurol as the co-surfactant and contained 0.5mg/mL tacrolimus. Blood and tissue concentrations of tacrolimus from two study groups (oral application of SMEDDS Tac and Prograf(®)) were determined using ELISA technique following tacrolimus administration in rats. There was no difference between area under the whole blood concentration-time curve in the SEDDM Tac group and the Prograf(®) group. Maximum concentrations of the drug were three times higher (P<0.05) in the SEDDM Tac group accompanied by a 3-fold earlier peak time. Elimination half-life was significantly lower in the SEDDM Tac group. Application of SMEDDS Tac increased tissue accumulation. Already after 15min, Tac levels of small intestine, liver, kidney, spleen, heart and bone marrow were significantly higher in the SMEDDS Tac group than in the Prograf(®) group (P<0.05). However, the Tac concentration in the kidney was significantly lower in the SMEDDS Tac group. Formulation of SMEDDS did not affect blood-brain barrier function. The SMEDDS is a potentially useful method for a local delivery of Tac to target organs. The selection of the optimum SMEDDS Tac composition might have advantage as an alternative oral dosage form for Tac.
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: Implantation of implantable cardioverter-defibrillators (ICD) from the left pectoral region is the standard therapeutical method. Increasing numbers of system revisions due to lead dysfunction and infections will consecutively increase the numbers of right-sided implantations. The reliability of devices implanted on the right pectoral side remains controversially discussed, and the question of testing these devices remains unanswered. METHODS: In a prospectively designed study all 870 patients (60.0+/-14 years, 689 male) who were treated with a first ICD from July 2005 until May 2012 and tested intraoperatively according to the testing protocol were analyzed. The indication for implantation was primary prophylactic in 71.5%. Underlying diseases included ischemic cardiomyopathy (50%), dilative cardiomyopathy (37%), and others (13%). Mean ejection faction was 27+/-12%. Implantation site was right in 4.5% and left in 95.5%. RESULTS: Five patients supplied with right-sided ICD (13%, p = 0.02 as compared to left-sided) failed initial intraoperative testing with 21 J. 3 patients were male. The age of the patients failing intraoperative testing with right-sided devices appeared higher than of patients with left-sided devices (p = 0.07). The ejection fraction was 28+/-8%. All patients reached a sufficient DFT <= 21 J after corrective procedures. CONCLUSION: Implantation of ICDs on the right side results in significantly higher failure rate of successful termination of intraoperatively induced ventricular fibrillation. The data of our study suggest the necessity of intraoperative ICD testing in right-sided implanted ICDs.
Journal of Cardiothoracic Surgery 04/2013; 8(1):77. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: BACKGROUND: The impact of minimized extracorporeal circulation (MECC) for emergency revascularization remains controversial. METHODS: A total of 348 patients underwent emergency CABG with MECC (n=146) or conventional extracorporeal circulation (CECC; n=175) between January 2005 and December 2010. Using propensity score matching after binary logistic regression, 100 patients, who underwent CABG with MECC could be matched with 100 patients, who underwent CABG with CECC. Primary outcome was 30-day mortality. RESULTS: Unadjusted 30-day mortality was 14.8% in patients with CECC and 6.9% in those with MECC (mean difference -7.9%; p=0.03). The adjusted mean difference (average treatment effect of the treated, ATT) after matching was -1.0% (95% CI -8.6 to 7.6; p=1.0). Intensive care unit stay (adjusted mean difference 1.0; 95% CI -0.2 to 3.2; p=0.70) and hospital stay (adjusted mean difference 1.0; 95% CI -2.0 to 3.6; p=0.40) did not show significant differences between both groups. The adjusted mean difference for postoperative low cardiac output syndrome was -1.1% (95% CI -7.3 to 7.1; p=0.83) without significant differences between CECC and MECC. Postoperative mechanical ventilation time, drain loss, postoperative rethoracotomy, postoperative neurological events, new onset renal replacement therapy and respiratory failure also had insignificant average treatment effects of the treated. In addition, all average treatment effects (ATEs) did not significantly differ between both groups. CONCLUSION: Using propensity score estimation and matching, we did not observe significant differences in terms of survival and further outcomes in patients who undergo emergency CABG with CECC or MECC, but our results call for further analysis.
Journal of Cardiothoracic Surgery 04/2013; 8(1):59. · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Bronchiolitis obliterans (BO) is a progressive and fatal disease after lung transplantation (LTX). Dysregulated growth factor-induced proliferation of myofibroblasts seems to be responsible for the development of BO. The aim was to confirm the efficacy of both inhibitors of receptor tyrosine kinases (RTKI) and of mammalian target of rapamycin (mTORI) after rat LTX. We used a rat model of left lung allo-transplantation (F344-to-WKY) to evaluate the effect of imatinib (RTKI; 20 mg/kg/day; postoperative day (POD) 0-100) alone or in combination with everolimus (mTORI; 2.5 mg/kg/day; POD 14-100). Non-treated animals were the reference. In non-treated rats, acute rejection (AR) peaked between POD 20 and 30 (19/19) and ended in chronic rejection (CR) on POD 60/100 (12/12). Imatinib alone did not prevent AR (6/6), but attenuated the degree of degenerated bronchioles on POD 30 (non-treated, 57%; imatinib, 4%), and increased the allografts free of CR on POD 60/100 (3/12). A Combination of imatinib and everolimus significantly reduced AR, attenuated fibrotic degenerated bronchioles (5%) and vessels (non-treated, 24%; combination therapy, 11%) on POD 30, and reduced fibrotic degenerated vessels (non-treated, 97%; combination therapy, 43%) and bronchioles (non-treated, 88%; combination therapy, 34%) on POD 60/100. Fifty percent of the animals were completely free of BO and vasculopathy. In conclusion, co-application of RTKI and mTORI attenuated the development of BO and vasculopathy. Thus, imatinib might be an interesting therapeutic approach after LTX.
Histology and histopathology 03/2013; · 2.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Chronic rejection (CR) in terms of bronchiolitis obliterans (BO) and vascular sclerosis (VS) still represents the major obstacle for pulmonary graft survival in the medium and long term course after lung transplantation (LTX). Aside from nonspecific stimuli, early acute rejection (AR) seems to be causative especially in cases of a late diagnosis or inadequate treatment. This study investigated the effects of FTY720, a new immunosuppressant that promotes lymphocyte sequestration into lymph nodes and Peyer's patches, on the development of CR after experimental LTX.
A total of 50 rats underwent allogenic (F344-to-WKY) and syngenic (WKY-to-WKY) left LTX. Group 1 animals had no treatment. Group 2 animals were administered FTY720 (3 mg/kg body weight per day) at the maximum time of AR (day 14) and continued up to day 100 after LTX. Group 3 animals were treated with the same dosage of FTY720 from day 0 to 100. The grades of AR and CR were classified according to the criteria of the International Society for Heart and Lung Transplantation.
Within 14 days after allogenic LTX, all nontreated rats developed early AR followed by severe CR with VS and BO. Similar data were observed for FTY720 treatment of existing AR (group 2). Only early administration of FTY720 (at the time of LTX) significantly reduced the proportion of animals with severe acute vascular rejection (P < .001). However, all of these allografts showed high-grade acute airway inflammation. After long-term application, the chronic inflammatory response was absent; none of the allografts developed BO and VS.
Only application of FTY720 immediately after LTX prevented lymphocyte recirculation and lung injury.