Bernhard Gohrbandt

Human cytokine responses to coronary artery bypass grafting with and without cardiopulmonary bypass

BACKGROUND Coronary artery bypass grafting (CABG) is associated with a systemic inflammatory response. This has been attributed to cytokine release caused by extracorporeal circulation and myocardial ischemia. This study compares the inflammatory response after CABG with cardiopulmonary bypass and after minimally invasive direct coronary artery bypass grafting (MIDCABG) without cardiopulmonary bypass. METHODS Cytokine release and complement activation (interleukin-6 and interleukin-8, soluble tumor necrosis factor receptors 1 and 2, complement factor C3a, and C1 esterase inhibitor) were determined in 24 patients before and after CABG or MIDCABG. The maximum body temperature, chest drainage, and fluid balance were recorded for 24 hours after operation. RESULTS Release of interleukin-6, interleukin-8, and tumor necrosis factor receptors 1 and 2 was significantly higher (p < or = 0.005) in the CABG group than the MIDCABG group just after operation. After 24 hours, a significant increase in interleukin-6 was also found in the MIDCABG group (p = 0.001) compared with preoperative value. Body temperature and fluid balance were significantly higher after CABG (p < or = 0.001). CONCLUSIONS Minimally invasive direct coronary artery bypass grafting represents a less traumatizing technique of surgical revascularization. The reduction in the inflammatory response may be advantageous for patients with a high degree of comorbidity.

Matched-pair analysis of conventional versus endoluminal AAA treatment outcomes during the initial phase of an aortic endografting program.

Purpose: To investigate whether endovascular stent-grafts implanted during the early phase of an aortic endografting program have advantages over conventional surgical procedures for treatment of infrarenal aortic aneurysm (AAA). Methods: In the first months of an endografting program, 37 patients (36 men; mean age 67.9 ± 7.1 years, range 55 to 86) underwent AAA repair with endovascular implantation of a Vanguard (n = 17) or Talent (n = 20) bifurcated stent-graft. Data collected during the perioperative period and in follow-up were compared retrospectively to a matched group of 37 elective surgical patients. Results: All endograft implantations were completed. Two type I and 6 type II endoleaks (21.6%) were seen postoperatively. Five type II sealed without intervention; 1 type I endoleak was corrected with an additional stent, but 1 type I and 1 type II endoleaks persisted despite attempts with coil embolization. Two (5.4%) endograft patients died during the perioperative period; however, this was not significantly different (p = 0.15) from the control group. In the mean follow-up of 12 ± 6 months for both groups, 1 (2.7%) late conversion was necessary at 2 years for aneurysm expansion in an endograft patient with an unsealed type I endoleak. Conclusions: In our learning curve experience with aortic endografting, postoperative morbidity and mortality were higher in endograft patients compared to conventionally treated controls. Only in the endograft group was reoperation required during follow-up. Careful monitoring with periodic imaging studies is mandatory after endoluminal AAA treatment.

Re: Cardiac retransplantation: is it justified in times of critical donor organ shortage? Long-term single-center experience

OBJECTIVE Survival after heart transplantation has improved significantly over the last decades. There are a growing number of patients that require cardiac retransplantation because of chronic allograft dysfunction. With regard to the critical shortage of cardiac allograft donors the decision to offer repeat heart transplantation must be carefully considered. METHODS Since 1983 a total of 807 heart transplantations have been performed at our institution. Among them 41 patients received cardiac retransplantation, 18 patients because of acute graft failure and 23 because of chronic graft failure. Data were analyzed for demographics, morbidity and risk factors for mortality. The acute and chronic retransplant group was compared to those patients undergoing primary transplantation. RESULTS The mean interval between primary transplantation and retransplantation was 1.9 days in the acute and 6.7 years in the chronic retransplant group. Mean follow-up was 6.9 years. Baseline characteristics were similar in the primary and retransplant group. Actuarial survival rates at 1, 3, 5 and 7 years after primary cardiac transplantation compared to retransplantation were 83, 78, 72 and 64% vs 53, 50, 47 and 36%, respectively (p<0.001). Early mortality after acute retransplantation was significantly higher compared to late retransplantation (10/18, 55.6% vs 4/23, 17.4%, p=0.011). Major causes of death were acute and chronic rejection, infection and sepsis. CONCLUSIONS Cardiac retransplantation is associated with lower survival rates compared to primary transplantation. However, results after retransplantation in chronic graft failure are significantly better compared to acute graft failure. Therefore, we consider cardiac retransplantation in chronic graft failure a justified therapeutic option. In contrast, patients with acute graft failure seem to be inappropriate candidates for cardiac retransplantation.

Lung and heart-lung transplantation in children and adolescents: a long-term single-center experience.

BACKGROUND Pediatric lung transplantation (LTx) remains a challenge for a highly selected group of patients. The requirements for immunosuppressive therapy and the associated risks must be weighed against the long-term prognosis of this operation. Therefore, we retrospectively analyzed our experience after 53 lung and heart-lung transplantations (HLTx) in children. METHODS All pediatric patients <18 years of age who underwent LTx (n = 37) and HLTx (n = 16) at our institution were included in this study. We analyzed indications for transplantation, survival rates and causes of death. Herein we assess pediatric-specific challenges in comparison to adults. RESULTS Thirty-day mortality was 13.2%. Kaplan-Meier survival rates at 1, 3, 5 and 10 years were 69%, 64%, 44% and 39%, respectively. Main indications for transplantation were cystic fibrosis and congenital heart disease with Eisenmenger syndrome. Other diagnoses were retransplantation, primary pulmonary hypertension and pulmonary fibrosis. The main causes of death were infection and chronic graft failure. Reduced-size transplantation was performed in 42% of double-lung transplantation (DLTx) patients without negatively impacting survival. Six patients received pulmonary retransplantation, 1 of whom died early. CONCLUSIONS Pediatric transplantation is a feasible therapeutic option when undertaken by an experienced team. It should be offered to the small patient population suffering from end-stage pulmonary disease. The limited number of pediatric donor organs can be overcome by using reduced-size organs. However, the management of pediatric-specific complications and therapeutic requirements is essential for positive long-term results after LTx in these patients.

Should lungs from donors with severe acute pulmonary embolism be accepted for transplantation? The Hannover experience.

Lung transplantation has evolved to an accepted treatment modality for patients suffering from end-stage lung disease. The number of listed patients waiting for a lung transplant is dramatically higher than the number of available donor organs, which contributes to a 1-year mortality on the waiting list of approximately 20% and of 40% after 2 years of listing. Many strategies aiming for an increase of donor organs have been discussed controversially and are partially under clinical examination, such as the utilization of lungs from non–heartbeating donors or the concept of living-related lung transplantation. Other approaches to the problem are even more experimental, such as pulmonary xenotransplantation. During the 2003 annual meeting, The International Society for Heart and Lung Transplantation discussed the issue of redefining current lung donor criteria and the concept of using marginal donor organs for selected recipients in a main session. Many groups presented their outcomes following lung transplantation using lungs from donors who were heavy smokers, from donors with onset of fatal asthma, or from elderly donors up to 77 years of age. One major consensus of this intense discussion, however, was that some donors are still considered as inadequate for lung donation, such as patients who show signs of severe pneumonia or aspiration as well as those who died from fulminant pulmonary embolism. Here, we report on 3 cases in which lung grafts from patients with fatal severe acute pulmonary embolism were successfully transplanted. We further describe a novel strategy of in situ retrograde lung flush perfusion that we are routinely using in our clinical program now, which is of special importance for lung graft retrieval from donors with acute pulmonary embolism.

An infection with linezolid-resistant S. aureus in a patient with left ventricular assist system

We report an infection with a linezolid-resistant S. aureus in a patient with a left ventricular assist system. Linezolid should be used with caution when invasive devices or foreign materials are in place or therapeutic courses last longer than 14 d. Previous cases of linezolid-resistant S. aureus are summarized.

Glutathione preconditioning ameliorates mitochondria dysfunction during warm pulmonary ischemia-reperfusion injury

OBJECTIVES Reduced glutathione (GSH) has been shown to improve pulmonary graft preservation. Mitochondrial dysfunction is regarded to be the motor of ischemia-reperfusion injury (IR) in solid organs. We have shown previously that IR induces pulmonary mitochondrial damage. This study elucidates the impact of GSH preconditioning on the integrity and function of pulmonary mitochondria in the setting of warm pulmonary IR. METHODS Wistar rats were subjected to control, sham, and to two-study-group conditions (IR30/60 and GSH-IR30/60) receiving IR with or without GSH preconditioning. Rats were anesthetized and received mechanical ventilation. Pulmonary in situ clamping followed by reperfusion generated IR. Mitochondria were isolated from pulmonary tissue. Respiratory chain complexes activities (I-IV) were analyzed by polarography. Mitochondrial viability (Ca2+-induced swelling) and membrane integrity (citrate synthase assay) were determined. Subcellular-fractional cytochrome C-content (Cyt C) was quantified by enzyme-linked immunosorbent assay (ELISA). Mitochondrial membrane potential (ΔΨm) was analyzed by fluorescence-activated cell sorting (FACS) after energizing and uncoupling. Inflammatory activation was determined by myeloperoxidase activity (MPO), matrix-metalloproteinase 9 (MMP-9) activity by gel zymography. RESULTS Pulmonary IR significantly reduced mitochondrial viability in combination with ΔΨm hyper-polarization. GSH preconditioning improved mitochondrial viability and normalized ΔΨm. Cyt C was reduced after IR; GSH protected from Cyt C liberation. Respiratory chain complex activities (I, II, III) declined during IR; GSH protected complex II function. GSH also protected from MMP-9 and neutrophil sequestration (P>.05). CONCLUSIONS GSH preconditioning is effective to prevent mitochondrial death and improves complex II function during IR, but not mitochondrial membrane stability. GSH-mediated amelioration of ΔΨm hyper-polarization appears to be the key factor of mitochondrial protection.

Lung Preservation With Perfadex or Celsior in Clinical Transplantation: A Retrospective Single-Center Analysis of Outcomes.

Background Despite improvement of lung preservation by the introduction of low-potassium dextran (LPD) solution, ischemia-reperfusion injury remains a major contributor to early post-lung transplant graft dysfunction and mortality. After favorable experimental data, Celsior solution was used in our clinical lung transplant program. Data were compared with our historic LPD cohort. Methods Between January 2002 and January 2005, 209 consecutive lung transplantations were performed with LPD. These were compared to 208 transplants between February 2005 and September 2007 with Celsior. Endpoints included posttransplant PaO2/FiO2 ratio at different timepoints after intensive care unit (ICU) admission, posttransplant ventilation time, ICU stay and 30-day mortality, follow-up survival, and bronchiolitis obliterans syndrome-free survival. Results Ratios of sex, urgency status, type of procedure, length of posttransplant ICU stay, and age did not show significant differences between the 2 groups. Mean ischemia times were significantly longer in the Celsior group (LPD, 355 ± 105 minutes vs Celsior, 436 ± 139 minutes, P < 0.001). Overall 3-year-survival (LPD, 66.5% vs Celsior, 72.0%; P = 0.25) was nonsignificantly improved in the Celsior cohort. Conclusions A trend toward better survival (P = 0.09) and increased freedom from bronchiolitis obliterans syndrome (P = 0.03) was observed in the Celsior group despite prolonged ischemic times compared with LPD. Lung preservation with Celsior is safe and effective and may carry advantages.

Exogenous surfactant instillation in lung donors to reduce early graft dysfunction

Background: Application of exogenous surfactant has been proposed to ameliorate lung ischemia-reperfusion injury. Experimentally, donor pretreatment has been favored over posttransplant application. We now report on the first prospective randomized clinical study of donor surfactant instillation in lung transplantation. Methods: Lung donors were randomly assigned to the surfactant (Surf, n=14) or the control group (Co, n=15). Bovine surfactant (100 mg/kg BW) was instilled segmentally via bronchoscopy within 30 min before organ harvest. Diagnostic bronchoalveolar lavage (BAL) was performed before surfactant instillation and 8 h after reperfusion of the graft. Surface-tension lowering properties of surfactant and the ratio of small to large surfactant aggregates (SA/LA) were determined as indicators for preservation of surfactant function from BAL fluid. Clinical outcome of the surfactant group was compared to 187 consecutive cases with otherwise similar treatment. Results: Surface tension of BAL fluid after transplantation was slightly increased in the Surf group but markedly increased in the Co group, indicating loss of surfactant function (9.6±2.1 vs. 17.5±1.9 mN/m; Surf vs. Co, respectively; P<0.05). The SA/LA ratio, as a marker for metabolic conversion of the surfactant material, was high in both groups before explant (0.86±0.4 vs. 0.78±0.31). This ratio was improved after transplant in Surf lungs, but further deteriorated in controls (0.42±0.28 vs. 1.58±0.44). Early clinical outcome showed no death in both groups and was without significant differences between groups due to low sample size, but when compared to our overall recipient population, spirometry in the Surf group revealed higher FEV1 2 weeks after transplant (2.81±0.71 vs. 1.77±0.91; P<0.05). Conclusion: Exogenous surfactant is safe and markedly improves post transplant surfactant function. Its application before organ harvest is therefore encouraged, especially in borderline donors.

Lung Perfusion in Clinical Heart-Lung Transplantation

The initial steps of cardiac transplantation were conducted more than 100 years ago by Carerel and Guthrie in 1905, employing an acute model with anastomosis of the neck vessels to cardiac structures.1 Reports of the cardiac function do not exist. In 1933, Mann, Pristley, and Markowitz published on donor hearts being connected to the neck vessels of dogs in various different ways. None of them allowed an active support of the cardiac graft to the recipient’s circulation. The functional status of the grafts remains unknown. The animals survived not longer than 8 days.1,2 In 1940, Demikhov initialized experiments with hearts transplanted into the inguinal position and concluded from his recent and other former results that the heart can only function actively if it would be transplanted into the chest due to its anatomical and physiological features. When it would be transplanted to vessels of the neck or inguinal region, it remained completely dependent on the recipient’s blood without any active movement of the blood.2