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Friedrich W Mohr

Publications and source records attributed to Friedrich W Mohr.

At least 19 recordsLinked to original sources
PubMed2007

Seven-year follow-up after minimally invasive direct coronary artery bypass: experience with more than 1300 patients.

BACKGROUND: Minimally invasive direct coronary artery bypass (MIDCAB) for revascularization of the left anterior descending artery has become a routine operation. Here we present the experience after more than 1300 MIDCAB procedures with up to 7 years of follow-up. METHODS: All patients undergoing standard MIDCAB between 1996 and 2004 were included. Long-term follow-up information about health status, major cardiac and cerebral adverse events, and freedom of angina was collected annually by a questionnaire or personal contact. Preoperative, intraoperative, and postoperative data could be completed for all 1347 patients. Five-year follow-up was available for 450 patients and 7-year follow-up for 194 patients. RESULTS: Mean age was 63.2 years (range, 25 to 92 years) and mean ejection fraction was 0.61 +/- 0.14. In 23 patients (1.7%), intraoperative conversion to sternotomy or CPB, or both, was necessary. Early postoperative mortality was 0.8% (n = 11), and 0.4% (n = 5) had a perioperative stroke. A routine postoperative angiogram in 709 patients showed 95.6% early graft patency. Short-term target vessel reintervention was needed 55 patients (4.1%): 10 had percutaneous transluminal coronary angioplasty/stent and 45 had reoperation. A repeat angiogram at the 6-month follow-up was available in 350 patients and demonstrated 94.3% graft patency. Kaplan-Meier analysis revealed a 5-year survival of 91.9% (95% confidence interval [CI], 90.1% to 93.8%) and a 7-year survival of 89.4% (95% CI, 86.7% to 92.1%). The freedom of major adverse events and angina was 89.5% (95% CI, 87.4% to 91.5%) after 5 years and 83.3% (95% CI, 79.0% to 87.5%) after 7 years. CONCLUSIONS: MIDCAB can be safely performed with low postoperative mortality and morbidity. The excellent short-term and long-term survival as well as freedom from major adverse cardiac and cerebral events and angina compare favorably with stenting and conventional surgery.

Adult↗
PubMed2006

Replacing cardiopulmonary bypass with extracorporeal membrane oxygenation in lung transplantation operations.

OBJECTIVE: Cardiopulmonary bypass (CPB) support is required in some lung transplantation (LTX) operations. CPB support and full-dose heparin increases the risks of bleeding and early graft dysfunction. We report our experiences of replacing CPB with heparin-bonded low-dose heparin extracorporeal membrane oxygenation (ECMO) support in LTX surgery. METHODS: From 2003 to 2005 forty-seven patients were transplanted. Thirty-seven LTX patients were retrospectively evaluated for this study (10 patients were excluded due to heart-lung-, lung-kidney transplantation, LTX with bypass grafting, and ASD closure or emergency CPB support). Extracorporeal circulation support was necessary in 40% of the 37 LTX patients due to severe primary or secondary pulmonary hypertension (P or SPHTN), right heart dysfunction, or hemodynamic instability. There were seven LTX procedures with CPB and eight implantations with ECMO support. CPB (high-dose heparin) and ECMO support (ACT 160-220 s) was always set up through femoral veno-arterial canulation. All patients had limited access thoracotomies without transsection of the sternum. Normothermia was maintained in all patients. CPB patients: PPH 15%, COPD 15%, IPF with mean PAP>40 mmHg 70%. ECMO patients: PPH 13%, COPD 13%, IPF with severe PAP pressure elevation 74%. RESULTS: In patients undergoing LTX for PPH, the ECMO support was directly extended into the post-operative period. Packed red blood cell (PRBC) transfusion requirements during the operation and the first 24h were 13.25+/-1.6 PRBC units versus 5.1+/-2.8 PRBC units on CBP (p=0.02). Operative time was longer (p=0.11) in the ECMO LTX (451 min+/-76 vs 346+/-140). The increased 90-day mortality rate of the ECMO patients showed a trend toward significance (p=0.056), which was related to infectious complications (3 vs 1 patient). Severe graft ischemia/reperfusion injury occurred in 9% in the CPB versus 13% in the ECMO group. The 1-year survival was significantly reduced in ECMO patients (p=0.004, log-rank test). CONCLUSIONS: The advantages of femoral canulation rather than conventional central connections in lung transplantation procedures led to an undisturbed operative field. A significantly higher blood product amount was required in ECMO patients, which might lead to increased infection and mortality rates. CPB, obviously, should remain the standard support technique if extracorporeal circulation is required in lung transplantation surgery.

Adult↗
PubMed2006

Perspectives in endoscopic cardiac surgery.

Surgical telemanipulators are obviously used in cardiac surgery to provide the surgeon in a confined space the same stereoscopic vision, full dexterity, unimpaired hand-eye alignment and tactile feedback as in open surgery. This is the basic concept that enables the controlled fine soft tissue manipulation that is needed in bypass grafting and valve surgery. In 2005, a total of 2984 cardiac procedures were performed worldwide using the da Vinci system. This includes totally endoscopic coronary artery bypass grafting (TECAB), mitral valve repair (MVR) procedures, ASD closure and cardiac tissue ablation for atrial fibrillation.

Cardiac Surgical Procedures↗
PubMed2006

Pharmacodynamic monitoring of the immunosuppressive therapy in patients after heart transplantation: whole blood flow cytometric analysis of lymphocyte function.

Despite therapeutic monitoring and daily measurements of blood concentrations (pharmacokinetics) of immunosuppressive medications, immunosuppressive therapy remains still a challenge after heart transplantation (HTx) due to drug interactions, toxicities and individual responses to drug effects. We established whole blood flow cytometric assays of lymphocyte function to assess the pharmacodynamics of immunosuppressive therapy and investigated both pharmacokinetic and pharmacodynamic approaches after HTx. Our results showed that pharmacodynamic measurements provide a more direct assessment of the functional activity of immunosuppressants on immune cells compared to drug level monitoring alone. The information from both pharmacokinetic and pharmacodynamic monitoring has the potential to increase the efficacy and safety of individual immunosuppressive therapy after HTx.

Aged↗
PubMed2006

Minimally invasive transapical beating heart aortic valve implantation--proof of concept.

OBJECTIVE: To evaluate the feasibility of minimally invasive transapical beating heart aortic valve implantation (TAP-AVI) for high-risk patients with aortic stenosis. METHODS: TAP-AVI was performed via a small anterolateral minithoracotomy with or without femoral extracorporeal circulation (ECC) on the beating heart. A pericardial xenograft fixed within a stainless steel, balloon expandable stent (Cribier-Edwards, Edwards Lifesciences, Irvine, CA, USA) was used. Thirty consecutive patients (82 +/- 5.1 years, 21 (70%) female) were operated from 02/06 until 09/06 at one center using fluoroscopic and echocardiographic visualization. Average EuroSCORE predicted risk for mortality was 27 +/- 12%. RESULTS: Valve positioning was successful in 29 patients and one required early conversion to full sternotomy. Implantation (8 mm x 23 mm and 22 mm x 26 mm valves) was performed on the beating heart during brief periods of rapid ventricular pacing. ECC was applied in 13 patients. Neither coronary artery obstruction nor migration of the prosthesis was observed and all valves displayed good hemodynamic function. Echocardiography revealed minor paravalvular leakage in 14 patients (trace in three, mild in nine and moderate in two). Three patients (10%) died, one on postoperative day (POD) three secondary to preoperative global myocardial failure and two on POD 18 and 86 due to abdominal complications. CONCLUSIONS: Minimally invasive beating heart TAP-AVI is feasible. Initial results are encouraging in view of the high-risk profile of the patients. Long-term studies as well as randomized protocols are required.

Aged↗
PubMed2006

Affects of immunosuppression on circulating dendritic cells: an adjunct to therapeutic drug monitoring after heart transplantation.

OBJECTIVES: Recent evidence emerges dendritic cells (DCs) as pharmacological targets of immunosuppressive drugs. Therefore, in this study we monitored DCs in peripheral blood to compare the effects of calcineurin inhibitors (CNI: cyclosporine, tacrolimus) and mammalian target of rapamycin inhibitors (sirolimus, SRL, everolimus, ERL) basis-immunosuppressive therapies in human heart transplanted (HTx) recipients. METHODS: We compared HTx recipients which were converted from either CNI to ERL (severe renal dysfunction, n=8), or from SRL to ERL (approval of ERL for HTx, n=8) with 20 healthy human controls. Twenty four after the last CNI or SRL dose recipients were treated with ERL/BID on days 1-3. Peripheral blood was collected at trough in the morning before and on day 4 after conversion. Percentages of positive myeloid and plasmacytoid DC (m and pDC) subsets in peripheral blood were analysed by flow cytometry. The status of maturation was further characterised by flow cytometry analysis of % expression of CD83 and % expression of various intracellular cytokines (IL-1beta, TNF-alpha, IL-8, IL-12), respectively. RESULTS: HTx recipients had higher % positive mDCs regardless the immunosuppressive therapy compared to controls (p<0.05). Whereas, % positive pDCs were only significantly lower in recipients converted from CNI to ERL compared to controls (p<0.05). The data consolidate the finding that the subset ratio pDCs/mDCs was lower in recipients compared to controls. But after conversion from CNI or SRL to ERL the ratio increased towards pDCs. Percentages of expression of CD83 on mDCs were not different among the recipient groups and controls. Recipients with CNI and SRL had higher % expression of IL-12 and lower % expression of IL-1beta compared to controls (p<0.05). However, after conversion to ERL % expression of both IL-12 and IL-1beta returned to control values in both groups. CONCLUSIONS: The results showed that analysis of immunosuppression of circulating DCs in peripheral blood may be an adjunct to therapeutic drug monitoring to optimize immunosuppressive therapy after HTx.

Antigens, CD↗
PubMed2006

The influence of immunosuppressive drugs on T- and B-cell apoptosis via p53-mediated pathway in vitro and in vivo.

BACKGROUND: This study was designed to assess the effects of calcineurin and inosine-5-monophosphate-dehydrogenase inhibitors on p53-mediated-apoptosis in T- and B-cells in vitro and in human heart-transplanted recipients (HTx-R). METHODS: For in vitro experiments, peripheral blood from healthy volunteers was collected and treated either with 1 microM cyclosporin A (CsA; n = 6), 10 microM mycophenolic acid (MPA; n = 6) or 100 nM tacrolimus (TRL; n = 6). For the second part, peripheral blood was collected from HTx-R undergoing CsA-MPA (n = 11) or TRL-MPA (n = 11) therapy before (0 hr) and after (2 hr) acute drug application and from healthy volunteers (n = 11) without drug therapy. Whole blood (part 1+2) was stimulated (24 hr) with eight different concentrations of actinomycin-D (0-800 nM), an apoptosis inductor acting via p53-pathway. Apoptotic lymphocytes were measured by TUNEL and expression of Annexin-V using FACS. Drug effects were calculated by taking the effects of actinomycin-D as baseline values. RESULTS: In vitro drug treatment with CsA, MPA, and TRL significantly (P < 0.05) decreased the apoptotic effect of actinomycin-D in T-cells in a noncompetitive manner. In HTx-R undergoing drug therapy, there was a similar antiapoptotic effect observed in both T- and B-cells (P < 0.05). Differences between 0 hr and 2 hr after acute drug application did not exist. Apoptosis induced by actinomycin-D can be completely blocked by caspase-inhibitor zVAD-FMK. CONCLUSION: Our results suggest that, in vitro and in HTx-R, an inhibition of calcineurin and inosine-5-monophosphate-dehydrogenase by CsA, TRL, or MPA lead to an inhibition of T-and B-cell apoptosis via p53-pathway. This assay may be helpful to provide insights into mechanisms of immunosuppressive drugs in regulation of apoptosis in lymphocytes.

Apoptosis↗
PubMed2006

Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress: the EPAS trial.

BACKGROUND: Statins and angiotensin type 1 (AT1) receptor blockers reduce cardiovascular mortality and morbidity. In the Endothelial Protection, AT1 blockade and Cholesterol-Dependent Oxidative Stress (EPAS) trial, impact of independent or combined statin and AT1 receptor blocker therapy on endothelial expression of anti-atherosclerotic and proatherosclerotic genes and endothelial function in arteries of patients with coronary artery disease were tested. METHODS AND RESULTS: Sixty patients with stable coronary artery disease undergoing elective coronary artery bypass grafting (CABG) surgery were randomized 4 weeks before surgery to: (A) control without inhibition of renin-angiotensin system or statin; (B) statin (pravastatin 40 mg/d); (C) AT1 blockade (irbesartan 150 mg/d); or (D) combination of statin and AT1 blocker in same dosages. Primary end point was a priori therapy-dependent regulation of an anti-atherosclerotic endothelial expression quotient Q including mRNA expression (in arbitrary units measured by real-time polymerase chain reaction) of endothelial nitric oxide synthase and C-type natriuretic peptide, divided by expression of oxidized low-density lipoprotein receptor LOX-1 and NAD(P)H oxidase subunit gp91phox in left internal mammary arteries biopsies obtained by CABG surgery; 49 patients completed the study. Statin therapy increased lnQ from 3.2+/-0.4 to 4.4+/-0.4 significantly versus control. AT(1) blockade showed a trend to increase lnQ to 4.2+/-0.5. Combination of statin and AT1 blocker further increased lnQ to 5.1+/-0.6, but a putative interaction of both therapies in lnQ was not significant. Furthermore, preoperative therapy with statin, AT1 blocker and their combination improved endothelial function in internal mammary artery rings. CONCLUSIONS: Statin and AT1 blocker therapy independently and in combination improve an anti-atherosclerotic endothelial expression quotient and endothelial function.

Angiotensin II Type 1 Receptor Blockers↗
PubMed2006

Patient prosthesis mismatch affects short- and long-term outcomes after aortic valve replacement.

OBJECTIVE: The aim of this study was to evaluate the impact of patient prosthesis mismatch (PPM) and additional risk factors on outcome after aortic valve replacement (AVR). METHODS: Four thousand one hundred and thirty-one patients who were operated between May 1996 and April 2004 were evaluated. One thousand eight hundred and fifty-six patients received bileaflet mechanical AVR and 2275 stented xenograft AVR. PPM was defined as severe if manufacturers effective orifice area (EOA) divided by body surface area (BSA) was <0.65 cm(2)/m(2) and as moderate in the range of 0.65-0.85 cm(2)/m(2). PPM, age, gender, EOA index, emergency indication for surgery (within 24h), EuroSCORE as well as requirement for additional procedures were tested. Univariate (Fisher's exact test) and multivariate logistic regression analysis as well as survival analysis (Kaplan-Meier) were performed. RESULTS: Severe PPM was present in 97 (2.4%) and moderate PPM in 1103 (26.7%) patients. PPM occurs more frequently with xenograft AVR. In-hospital mortality was 5.2% for severe, 10.6% for moderate and 6.9% with no PPM (p=0.018, OR 1.4). Moderate PPM was independently predictive for short- and long-term mortality. Further analysis revealed patient age >70 years (n=1589, p=0.002, OR 1.85), emergency indication (n=374, p<0.001, OR 4.4), EuroSCORE >10 (n=494, p<0.001, OR 4.7) and additional cardiac procedures (n=2049, p<0.001, OR 2.0) as predictors for adverse outcome after AVR. CONCLUSION: Severe PPM is rare; moderate PPM is present in a quarter of patients. PPM has a significant impact on short- and long-term mortality after AVR.

Aged↗
PubMed2006

Transapical approach for sutureless stent-fixed aortic valve implantation: experimental results.

OBJECTIVE: Percutaneous aortic valve implantation has been performed in patients with severe aortic stenosis judged as nonsurgical candidates. We evaluated a facilitated transapical antegrade approach for potential use in surgical high-risk patients. METHODS: A pericardial xenograft fixed within a 23-mm stent (Cribier-Edwards aortic prosthesis, Edwards Inc., Irvine, CA, USA) was implanted using a transapical approach in fifteen 35-45 kg pigs. A limited or a full sternotomy was used to transapically introduce a crimped valve through a 24-F sheath. Deployments were performed on the beating heart either with ventricular unloading using femoro-femoral cardiopulmonary bypass (CPB) or rapid ventricular pacing (RVP), all under fluoroscopic and echocardiographic visualization. RESULTS: All valves were successfully deployed at the target site with acceptable visualization of the noncalcified annulus. Valve migration occurred in six procedures (three distal and three retrograde) secondary to inadequate reduction of ventricular output, unfavorable annular anatomy, excessive crimping of the valve, and dislodgement by the delivery balloon. Exact positioning of the valve into the target area was confirmed by autopsy at the end of the procedures. Paravalvular leak was noted in five implants. CONCLUSIONS: The transapical approach provides a safe, accurate, and effective route for facilitated antegrade delivery of a stent-fixed valve. Advanced stent design will lead to better stability of the implant and may minimize the risk of paravalvular leakage in future. Identifying the appropriate population for human feasibility trials remains a challenge.

Animals↗
PubMed2006

Current percutaneous coronary intervention and coronary artery bypass grafting practices for three-vessel and left main coronary artery disease. Insights from the SYNTAX run-in phase.

OBJECTIVE: Percutaneous coronary intervention with drug-eluting stents is challenging coronary artery bypass grafting (CABG) as the gold standard for treatment of three-vessel and left main coronary disease. We evaluated the current practice pattern in hospitals throughout Europe and USA. METHODS: To qualify for participation in the SYNTAX (Synergy between PCI with TAXUS drug-eluting stent and Cardiac Surgery) study, a randomized trial comparing percutaneous coronary intervention with drug-eluting stent versus coronary artery bypass grafting for three-vessel and left main disease, 104 centers were asked to provide their case volume in 3 months in 2004. Anonymous procedural data were collected. RESULTS: A total of 12,072 patients were recorded. Coronary artery bypass grafting was the most frequently performed procedure (N=8895, 74%). Three-vessel disease (3VD) predominated in this population (N=8532, 71%) versus left main (N=3540, 29%). In the 3-month period, per center a mean of 8.3 patients with left main and 22.3 patients with three-vessel disease were treated by percutaneous coronary intervention, while 26.0 patients with left main and 60.3 patients with three-vessel disease were treated by coronary artery bypass grafting. In USA, percutaneous coronary intervention for left main and/or three-vessel disease was performed in 18% of the cases while this was performed in 29% of the cases in Europe. Of all CABG procedures, only 12% were done with total arterial grafting while 7% were treated with only venous grafts. CONCLUSIONS: In patients with multivessel or left main disease, still coronary artery bypass grafting remains the dominant revascularization strategy. Percutaneous coronary intervention is performed frequently without supporting data from the literature. Percutaneous coronary intervention for this indication is performed more often in Europe than in USA. Only a minority of the patients receives total arterial grafting in case of coronary artery bypass grafting. The SYNTAX trial with randomized and registry cohorts should provide guidance for selecting the preferred form of treatment.

Angioplasty, Balloon, Coronary↗
PubMed2006

Cytokine analysis to predict immunosuppression.

BACKGROUND: Recently, it has been realized that TH1/TH2 cytokine production offer the unique possibility to predict drug efficacy. However, there is still an incessant need to explore assay conditions and techniques of analyzing cytokines, which are specific and reliable for monitoring drug efficacy. METHODS: In this study we used the multiplex bead array technique to detect cytokines of TH1/TH2 cells in whole blood of heart transplanted (HTx) recipients. RESULTS: We found significantly different levels of cytokine expression in HTx recipients compared with cytokine levels in patients prior to HTx. Furthermore, particular cytokine levels were significantly decreased 2 h after drug dosing, compared with cytokine levels before dosing in mitogen-stimulated whole blood. CONCLUSIONS: Cytokine analysis with the multiplex array technique in mitogen-stimulated whole blood provides the possibility to predict immunosuppression.

Cyclosporine↗
PubMed2006

Transapical aortic valve implantation: an animal feasibility study.

BACKGROUND: Percutaneous aortic valve implantation has recently been performed in nonsurgical patients with severe aortic stenosis. Retrograde valve delivery has been problematic because of the size of the delivery system and concomitant peripheral vascular disease. We investigated a minimally invasive approach through the left ventricular apex for antegrade placement of a device-deliverable valve. METHODS: Transapical aortic valve implantation was performed using a 23-mm equine valve mounted on a stainless steel stent in 24 swine (weight range, 35 to 45 kg). A limited or full sternotomy approach was used to access the apex of the heart. The crimped valve was introduced through a sheath in the left ventricular apex. Fluoroscopy and echocardiography were used for guidance. Deployments were performed on the beating heart either with ventricular unloading using femoral extracorporeal circulation or rapid ventricular pacing. RESULTS: All valves were successfully delivered at the selected target site with acceptable visualization of the noncalcified aortic annulus. Valve migration occurred during eight deployments (two distal and six retrograde) secondary to persistent cardiac output, unfavorable annular anatomy, and dislodgement by the delivery catheter. Exact positioning of the nonmigrated valves at the aortic annulus was examined by necropsy of all animals at the end of the procedures. Paravalvular leak was noted in 14 of 18 (77.8%) valves remaining in situ. CONCLUSIONS: The transapical approach was used for the successful antegrade placement of a stented valve, obviating the technical problems associated with a large delivery system transiting the peripheral vascular system. Stent design contributing to paravalvular leak remains problematic.

Animals↗
PubMed2006

Bovine jugular vein conduit for right ventricular outflow tract reconstruction: evaluation of risk factors for mid-term outcome.

BACKGROUND: The bovine jugular vein conduit (Contegra [Medtronic, Inc, Minneapolis, MN]) is one option for right ventricular outflow tract reconstruction. We examined the effect of patient age, conduit size, hemodynamics, and cardiac malformation on early and mid-term outcome. METHODS: Seventy-eight bovine jugular vein implantations were performed over 5 years. Follow-up averaged 31 +/- 17 months. Risk factor and adverse event analyses for graft dysfunction were performed by multivariate logistic regression and Kaplan-Meier analysis. RESULTS: There was no early mortality. Two late deaths occurred after 9 and 15 months. Early postoperative echocardiography revealed bovine jugular vein regurgitation greater than 2+ in 10 patients, all of which had conduit dilatation, had received a 12-mm conduit, and had a right-ventricular-to-left ventricular pressure ratio greater than 0.6. Two additional patients had severe conduit incompetence develop at the 2-year follow-up. During follow-up, mean gradients increased from 15 to 23 mm Hg (p = 0.03) and stenosis at the distal anastomosis occurred in 25% of patients. Percutaneous interventions were performed in 19 patients (24.4%). Conduit exchange was required in 10 patients (12.8%) after a mean of 14.9 months for severe graft incompetence (8 patients) and progressive supravalvular stenosis (2 patients). Freedom from reoperation was 77.6% and 59.3% at 1 and 4 years for patients less than 1 year of age compared with 93.5% and 87.4% for patients older than 1 year of age (p < 0.001). Risk factors for reoperation were age less than 1 year, correction of truncus arteriosus, conduit size of 12 mm, and persistently elevated right-ventricular-to-left ventricular pressure ratio greater than 0.6 (p = 0.001 each). CONCLUSIONS: Bovine jugular vein implantation is associated with low reoperation and acceptable reintervention rate in patients older than 1 year of age. In infants with persistently elevated right ventricular pressure, reoperation rate was high and had to be compared with other established surgical options.

Adolescent↗
PubMed2006

Minimally invasive surgery for valve disease.

Heart valve surgery evolved since the early 1960s toward routine clinical application with good patient outcome. Different surgical techniques and valve prostheses have been developed. Thus standard procedures were continuously established. The different surgical procedures have now gained widespread clinical acceptance with good patient outcomes. Aortic valve stenosis and mitral valve incompetence are the most frequently acquired heart valve lesions in the western communities. Usually such lesions reach clinical significance in patients during their fifth to eighth decade of life. Standard surgical techniques of aortic valve repair and mitral valve replacement or repair result in persistent cure of the disease. Surgical access was gained using conventional lateral thoracotomies in the early days and later on using median sternotomy. Minimally invasive techniques, mostly by a partial sternotomy for the aortic and a lateral minithoracotomy for the mitral position, have been increasingly applied to improve patient outcome since the mid 1990s. At specialized centers these techniques have evolved as clinical standard allowing all different valve procedures to be safely performed. Patient recovery is fast leading to a significant improvement in the individual's quality of life. Minimally invasive valve surgery can be considered the standard approach and will reach more widespread clinical application.

Aortic Valve Stenosis↗
PubMed2006

Aprotinin decreases reperfusion injury and allograft dysfunction in clinical lung transplantation.

OBJECTIVE: Primary graft dysfunction caused by ischemia-reperfusion injury is one of the most frequent causes of early morbidity and death after lung transplantation. We hypothesized that the perioperative management with aprotinin decreases the incidence of allograft reperfusion injury and dysfunction after clinical lung transplantation. METHODS: Lung transplant databases of two transplant centers were used to investigate the incidence of severe post-transplant reperfusion injury (PTRI). We examined data of 142 patients who underwent either single lung (81) or bilateral sequential lung (61) transplantation for COPD, idiopathic pulmonary fibrosis, cystic fibrosis, and miscellaneous lung disorders between 1997 and 2000. Thirty patients were excluded due to heart-lung transplantation or lung transplantation for Eisenmenger's disease, re-transplantation, rejection, or deviation from the standardized triple immunosuppression protocol. The data of remaining 112 patients (control group, 64% single lung, 36% sequential bilateral lung transplants) were compared to the prospectively collected data of 59 lung transplant patients over the last 5 years. All of these 59 patients were managed perioperatively with aprotinin infusion. In addition, Euro-Collins-aprotinin procurement solution (Apt-EC group) was used for 50 donor lungs (58% single lung, 42% sequential bilateral lung transplants). Aprotinin in combination with low-potassium dextran (LPD) flush solution (Apt-LPD group) was used for the procurement of 34 lungs (59% single lung, 41% sequential bilateral lung transplants). The International Society of Heart and Lung Transplantation (ISHLT) grade III injury score was used for the diagnosis of severe PTRI, which is based on a PaO(2)-FIO(2) ratio of less than 200 mmHg. RESULTS: Severe reperfusion injury grade III was observed in 18% of the control group. ECMO support was required in 25% of these patients. The associated mortality rate was 40%. Correlating factors for PTRI were donor age greater than 35 years (45%, p=0.01, mean age 38+/-8) and recipient pulmonary artery systolic pressure greater than 60 mmHg (48%, p<0.05). Lung graft ischemic times (231+/-14 min) and intraoperative techniques (cardiopulmonary bypass in 12%) were not associated with negative outcomes. Despite longer ischemic times (258+/-36 min and 317+/-85 min, respectively) and older donors (42+/-12 years and 46+/-12 years, respectively) in the aprotinin patient groups (Apt-EC and Apt-LPD group), the incidence of PTRI was markedly lower (6% and 9%, respectively). There was no mortality in the Apt-EC group and one patient died in the Apt-LPD group due to PTRI-induced graft failure. CONCLUSIONS: Severe PTRI increased short-term morbidity and mortality. The incidence of reperfusion injury was not dependent upon the duration of donor organ ischemia. The use of aprotinin in the perioperative patient management in lung transplantation had strong beneficial effects on the patient outcomes and decreased the incidence of post-transplant ischemia-reperfusion injury significantly.

Adult↗
PubMed2006

Both T-786C and G894T polymorphism of endothelial nitric oxide synthase affect in-vitro endothelium-dependent relaxation of internal mammary artery rings from patients with coronary artery disease.

OBJECTIVES: Polymorphisms of endothelial nitric oxide synthase (eNOS) gene in the promoter (T-786C) and exon 7 (G894T) have been suggested to attenuate endothelial function. As it is unknown whether these polymorphisms, on top of classical risk factors, further deteriorate endothelium-dependent vasomotion, we aimed to elucidate the impact of both polymorphisms on the ex-vivo vasomotor function of left internal mammary artery rings from patients with coronary artery disease (CAD) undergoing coronary bypass surgery (CABG). METHODS: Mammary artery rings from 51 consecutive patients with CAD were obtained during elective CABG. Endothelium-dependent ring relaxation was measured in vitro in an organ chamber using acetylcholine (10 to 3 x 10 mol/l). Polymorphisms were determined by polymerase chain reaction restriction length polymorphism. RESULTS: Thirty-three per cent of patients were positive for the T-786C polymorphism, 25% for the G894T polymorphism, and 18% carried mutated alleles in both loci. Maximal acetylcholine-induced ring relaxation was 46.7+/-3.2% in T-786C, 59.6+/-4.2% in G894T, and 66.7+/-7.4% in T-786C/G894T compared with 94.9+/-2.0% in wild-type subjects (P<0.05 versus T-786C, G894T, T-786C/G894T). Patients positive for an eNOS polymorphism with more than three cardiovascular risk factors displayed a further attenuation of acetylcholine-mediated relaxation (45+/-6 %) compared with having up to three risk factors (59+/-3%, P<0.05). CONCLUSION: In patients with CAD, in-vitro assessed endothelium-dependent relaxation of mammary arteries was significantly impaired in those positive for the T-786C or the G894T eNOS polymorphism. These results suggest that the presence of either one of the eNOS polymorphisms deteriorated endothelium-dependent vasodilatory capacity of large conduit vessels on top of classical risk factors in patients with CAD.

Aged↗