Biomedical subjects
Publications and source records attributed to Axel Haverich.
We hereby present our experiences with arterial cannulation through the aneurysm in patients with thoracoabdominal aortic aneurysm. This can be a good option for thoracoabdominal aortic aneurysm repair in patients with diseased peripheral arteries.
BACKGROUND: This study quantified the number of intraoperative microemboli in patients undergoing aortic arch surgery using selective cerebral perfusion (SCP) in comparison with those in patients undergoing ascending aortic replacement without circulatory arrest and SCP. METHODS: A transcranial Doppler monitoring of the medial cerebral artery was performed in 15 patients undergoing proximal arch replacement with SCP (SCP group) and 15 patients undergoing replacement of the ascending aorta (control group). RESULTS: There was no significant difference in the high-intensity transient signal counts between the SCP group and the control group at any phase. In the SCP group, 4.8% of microemboli occurred during cross-clamping, and only 0.6% occurred during SCP. In the control group, 4.6% occurred during cross-clamping. Most microemboli occurred after removing the cross-clamps in both groups; 92.2% in the SCP group and 92.1% in the control group. CONCLUSIONS: The present study demonstrated that outbreak frequency of microemboli during SCP was very low, and thus implies that the risk of embolic event that may be caused by SCP is very low.
BACKGROUND: Tissue-engineered pulmonary arteries could overcome the drawbacks of homografts or prosthetic conduits used in the repair of many congenital cardiac defects. However, the ideal scaffold material for tissue-engineered conduits is still subject of intensive debate. In this study, we evaluated an acellularized allogeneic matrix scaffold for pulmonary artery tissue engineering with and without in-vitro reseeding with autologous endothelial cells in the pulmonary circulation in a growing sheep model. METHODS: Ovine pulmonary arteries (n = 10) were acellularized by trypsin/ethylenediamine tetraacetic acid incubation. Autologous endothelial cells were harvested from carotid arteries, and the pulmonary conduits were seeded with endothelial cells. We implanted in-vitro, autologous, reendothelialized (group A, n = 5) and acellularized pulmonary conduits (group B, n = 5) in the pulmonary circulation. The animals were sacrificed 6 months after the operation. Explanted valves were examined histologically and by immunohistochemistry. RESULTS: The conduit diameter increased in both groups (group A, 44% +/- 11%; group B, 87% +/- 18%; p < 0.05). In group A, however, a proportional increase in diameter was present, whereas in group B, a disproportionate increase resulting in aneurysm formation was observed. Histologically, the conduit wall integrity was destroyed in group B and preserved in group A. In group B, the extracellularmatrix degenerated with a reduced amount of collagens and proteoglycanes. Furthermore, no elastic fibers were detectable. In contrast, the extracellularmatrix in group A was close to native ovine tissue. CONCLUSIONS: Tissue-engineered pulmonary conduits (autologous endothelial cells and allogeneic matrix scaffolds) functioned well in the pulmonary circulation. They demonstrated an increase in diameter and an extracellular matrix comparable to that of native ovine tissue.
BACKGROUND: The aim of this study was to assess palmar microcirculation in a long-term follow-up after radial artery harvesting for coronary revascularization. METHODS: One hundred fourteen patients (100 male; aged 61.7 +/- 6.7 years; preoperative New York Heart Association 2.3 +/- 0.6, ejection fraction 61.4% +/- 13.9%) were included after undergoing elective coronary revascularization using the radial artery of the nondominant forearm with a nonpathologic Allen's test. Superficial and deep tissue oxygen saturation (SO2), postcapillary venous filling pressure (rHb), capillary blood flow, and capillary blood flow velocity were determined at a mean 25 +/- 5 months after surgery using a combined laser Doppler spectrophotometry system. RESULTS: At 2-mm tissue depth, there was a small, but significant, decrease of 3% of superficial SO2 at the thumb and the thenar eminence (D1: 75.3% +/- 8.9% versus 77.6% +/- 9.7%, p = 0.003; thenar: 71.5% +/- 10.5% versus 73.2% +/- 8.2%, p = 0.027). Deep palmar SO2 was changed significantly at 5 of 7 positions by 3%. Deep postcapillary venous filling pressure (8 mm) was significantly increased by 9% only at the fingertip of the fifth finger (112.4 +/- 49.7 versus 103.0 +/- 25.0, p = 0.033), while superficial capillary blood flow decreased by 13% at only 1 of 7 positions at the hypothenar eminence (242.0 +/- 153.6 versus 275.6 +/- 169.2, p = 0.009). Overall, only 2 of 56 positions exceeded a given threshold of 5% change of microcirculation. No clinical signs of malperfusion were found (postoperative New York Heart Association 1.1 +/- 0.4, p < 0.05), and no patient was impaired in daily palmar motor activity. CONCLUSIONS: Long-term objective evaluation of superficial and deep palmar microcirculation confirms that radial artery harvesting for coronary revascularization does not compromise palmar microcirculation.
BACKGROUND: Morbidity and mortality after coronary artery bypass graft surgery are directly related to specific preoperative risk factors. We assessed the influence of preoperative risk factors on the effect of pexelizumab, a C5 complement inhibitor, to reduce postoperative morbidity and mortality in this post hoc analysis of the Pexelizumab for Reduction in Myocardial Infarction and MOrtality in Coronary Artery Bypass Graft surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing coronary artery bypass graft surgery with cardiopulmonary bypass. METHODS: The composite endpoint of death or myocardial infarction or both through postoperative day 30 was examined in subpopulations of patients with pre-specified risk factors, which included diabetes mellitus, prior coronary artery bypass graft, urgent intervention, female sex, history of neurologic event, history of congestive heart failure, and two or more previous myocardial infarctions or a recent myocardial infarction. Stratified post hoc analyses were also performed on patients presenting with two or more and three or more of those risk factors. RESULTS: Pexelizumab significantly reduced the incidence of the composite endpoint of death or myocardial infarction through postoperative day 30 by 28% in patients with two or more risk factors (p = 0.004) and 44% in patients with three or more risk factors (p < 0.001). CONCLUSIONS: The C5 complement inhibitor, pexelizumab, reduced morbidity and mortality among high-risk patients undergoing coronary artery bypass grafting with cardiopulmonary bypass.
BACKGROUND: Prolonged cross-clamp time during cardiac surgery increases the risk of postoperative mortality and myocardial injury. This subanalysis from the pexelizumab for reduction of infarction and mortality in coronary artery bypass grafting surgery (PRIMO-CABG) trial, a phase III double-blind, placebo-controlled study of 3,099 patients undergoing on-pump coronary artery bypass graft surgery with or without valve surgery, assessed the impact of pexelizumab, an investigational C5 complement inhibitor, on postoperative outcomes after prolonged aortic cross-clamp time. METHODS: The composite endpoint of death or myocardial infarction through postoperative day 30 and death alone through days 30, 90, and 180 were examined in subpopulations of patients across different cross-clamp times. RESULTS: After prolonged cross-clamping (> or = 90 minutes), death, or myocardial infarction through day 30 and death through days 30, 90, and 180 were significantly increased in the intent-to-treat population and were even higher in patients with two or more prespecified risk factors, compared with all patients cross-clamped less than 90 minutes. Pexelizumab significantly reduced the incidence of death or myocardial infarction through day 30, and significantly reduced the incidence of mortality through day 180, in patients with two or more risk factors that required prolonged cross-clamp time. Pexelizumab also significantly reduced perioperative myocardial injury in all patients requiring prolonged cross-clamp time. CONCLUSIONS: In this retrospective, subgroup analysis, pexelizumab reduced postoperative morbidity and myocardial injury in patients with multiple risk factors who underwent prolonged cross-clamp time during coronary artery bypass surgery. The clinical benefit of pexelizumab may be related to the effect of complement inhibition in the presence of potential ischemic-reperfusion injury associated with prolonged aortic cross-clamp time.
BACKGROUND: Here we report our surgical experiences with aberrant right subclavian artery (ARSA) aneurysm in 8 patients. METHODS: Eight patients underwent surgical treatment for ARSA aneurysm between March 1994 and June 2005. The age of these patients ranged from 20 to 75 years. The mean size of the ARSA aneurysm was 3.3 cm, ranging from 2 to 5 cm. The ARSA aneurysm was completely resected through a left posterolateral thoracotomy after reconstruction of the right subclavian artery through the supraclavicular approach in 4 patients (group 1). The ARSA aneurysm was excluded through a left posterolateral thoracotomy without revascularization of the right subclavian artery in 2 patients (group 2). The distal site of the ARSA aneurysm was closed followed by revascularization through a median sternotomy, and the ARSA aneurysm was left as a blind sack in 2 patients (group 3). RESULTS: None of the patients in group 1 or 3 had any postoperative complications. In group 2, 1 had a steal syndrome caused by the exclusion of the ARSA aneurysm, and the other died of sepsis 2 months after the operation. CONCLUSIONS: Complete anatomical repair of the ARSA aneurysm could be performed through the combination of the supraclavicular approach and the left posterolateral thoracotomy, with excellent results. Exclusion of the ARSA aneurysm without revascularization resulted in a suboptimal outcome. Surgical results of simple closure of the ARSA followed by revascularization were uneventful, but the ARSA aneurysm was left as a blind sack.
BACKGROUND: We present our perioperative management of operable nonsmall-cell lung cancer invading the tracheobronchial bifurcation and the results obtained. METHODS: Fifty consecutive patients undergoing carinal surgery with radical lymphadenectomy over a 5-year period were studied. RESULTS: Eighteen patients (36%) were N2 and had chemoradiation (48 +/- 6 Gy) preoperatively. Surgery included 34 carinal pneumonectomies (24 right, 10 left), 11 carinal lobectomies (n = 6) or bilobectomies (n = 5), and 5 carinal resections, with (n = 3) and without (n = 2) reconstructions. Patients were ventilated through low tidal volume controlled techniques except during airway resection and reconstruction, during which the apneic (hyper) oxygenation techniques were used. High inspiratory oxygen concentrations, multiple collapse and reexpansions, hypoperfusion of the ipsilateral lung, and fluid overload were avoided. All patients but 1 were extubated in the operating room, 7 +/- 5 minutes after skin closure. Operative mortality (less than 30 days) and morbidity were 4% (n = 2) and 37% (n = 18), respectively. All resections but 1 (98%) R1 were complete. The number of resected nodes per patient was 9 +/- 2, and 7 (22%) of the 32 patients who had negative preoperative positron emission tomography results had micrometastatic mediastinal nodes. With a median follow-up of 38 months, actuarial 5-year and disease-free survivals were 51% and 47%, respectively. Disease-free survival was significantly affected by endobronchial extension (tracheobronchial angle invasion versus less than 0.5 cm from carina, p = 0.03) and nodal status (N0 versus N1-2, p = 0.02) in the multivariate analysis. CONCLUSIONS: Preoperative chemoradiation, carinal lobectomy, or left pneumonectomy, and radical lymphadenectomy do not worsen the therapeutic index of carinal surgery. The high incidence of micrometastatic nodes in positron emission tomography-negative patients justifies routine mediastinoscopy and radical lymphadenectomy.
OBJECTIVES: Intramyocardial transplantation of bone marrow-derived cells is currently under clinical evaluation as a therapy of heart failure. A major limitation of all clinical studies dealing with myocardial cell engraftment is the inability to track the fate of the transplanted cells. We present a clinically applicable technique using transesophageal echocardiography (TEE) of CliniMACS nanoparticle labeled transplanted CD133+ cells in ischemic hearts. METHODS AND RESULTS: CD133+ cells were isolated from human bone marrow by CliniMACS magnetic bead selection. Positive (5 x 10(6) cells) cells were transplanted into porcine ischemic myocardium (n = 6). Control animals (n = 5) received medium injection. TEE was performed to demonstrate the distribution of the cells during and 8 weeks after the procedure. Accumulations of labeled CD133+ cells of adjacent injections in the myocardium were discriminatively identified by TEE. CONCLUSIONS: TEE is an elegant method for real-time documentation of successful transplantation and cell colony localization of magnetically labeled CD133+ cells in the ischemic myocardium. Our method should be of special interest for TEE-guided transcatheter injection of cells.
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OBJECTIVES: The potential role of glycine in combination with standard lung preservation with low-potassium dextran solution in lung ischemia-reperfusion injury has not been investigated in a preclinical porcine transplant model. METHODS: In a control group (n = 6), donor lungs were flushed with 1 liter of low-potassium dextran solution. In a second group (LPD-glyc, n = 6), low-potassium dextran solution was supplemented with 3.75 g of glycine. In a third group (IV-glyc, n = 6), donor preconditioning was performed by intravenous administration of 3.75 g glycine 1 hour before low-potassium dextran preservation. Grafts were stored in low-potassium dextran at 4 degrees C for 24 hours. Posttransplant graft function was assessed throughout a 7-hour observation period. RESULTS: In the control group, 2 recipients died of right-sided heart failure caused by severe ischemia-reperfusion injury. All animals of the glycine groups survived the entire observation period. Pulmonary vascular resistance remained significantly (P < .01) lower in both glycine groups when compared with controls. At the end of the observation period pulmonary vascular resistance in the control group was higher (P < .01) compared with the glycine groups (1310 +/- 319 dyn x sec x cm(-5) vs 879 +/- 127 dyn x sec x cm(-5) [LPD-glyc] vs 663 +/- 191 dyn x sec x cm(-5) [IV-glyc]). Changes of lung tissue water content were lower in the IV-glyc group compared with the LPD-control (P < .01) and LPD-glyc lungs (P < .05). Oxygenation (PO2/FiO2) was higher in the IV-glyc group compared with the LPD-glyc and control lungs (445 +/- 110 mm Hg vs 388 +/- 124 mm Hg [P < .01] vs 341 +/- 224 mm Hg [P < .001], respectively). DISCUSSION: Modification of low-potassium dextran solution with glycine or donor preconditioning ameliorates ischemia-reperfusion injury in lung transplantation. This intriguing approach merits further evaluation with respect to the mechanisms involved and may improve results in clinical lung preservation.
BACKGROUND: Worsening of lung failure in patients awaiting a lung transplantation might lead to ventilation-refractory hypercapnia and respiratory acidosis. Most transplant centers consider pretransplantation extracorporeal membrane oxygenation as a contraindication for lung transplantation because of the poor outcome. We have, for the first time, applied the novel pumpless interventional lung assist NovaLung for bridge to lung transplantation in patients with severe ventilation-refractory hypercapnia. We report on our initial experience. METHODS: Between March 2003 and March 2005, 176 lung transplantations were performed, of which 60% were high-urgency lung transplantations. Twelve of the high-urgency recipients had severe ventilation-refractory hypercapnia and respiratory acidosis. These patients were connected to the novel pumpless interventional lung assist NovaLung for bridge to lung transplantation. RESULTS: The length of interventional lung assist NovaLung support was 15 +/- 8 days (4-32 days). PaO2, pH, and PaCO2 levels in arterial blood prior to interventional lung assist NovaLung implantation were 71 +/- 27 mm Hg, 7.121 +/- 0.1, and 128 +/- 42 mm Hg, respectively. Six hours after interventional lung assist NovaLung implantation, PaO2, pH, and PaCO2 levels had changed to 83 +/- 17 mm Hg (ns), 7.344 +/- 0.1 (P < .05), and 52 +/- 5 mm Hg (P < .05), respectively. Four patients died of multiorgan failure, 2 patients before and 2 after lung transplantation. Thus, 10 out of 12 patients were successfully bridged to lung transplantation, and 8 are still alive (1-year survival, 80%). CONCLUSIONS: This report suggests that interventional lung assist NovaLung implantation is an effective bridge to lung transplantation strategy in patients with ventilation-refractory hypercapnia.
OBJECTIVE: Bronchiolitis obliterans syndrome has become the most limiting factor for long-term outcome after lung transplantation. Redo lung transplantation was performed for end-stage bronchiolitis obliterans syndrome. Long-term outcome was compared with that after primary lung transplantation as well as with other indications for retransplantation. METHODS: Of 614 lung transplantation procedures performed at our institution, 54 (8.5%) were redo transplants. These were stratified into different groups according to the indication for redo transplantation, including chronic graft failure/bronchiolitis obliterans syndrome, acute graft failure, and posttransplantation airway complications. Long-term survival was compared with that of the primary lung transplantation cohort, thereby respecting the need for pretransplant mechanical ventilatory support in a subanalysis. In addition, recurrence of bronchiolitis obliterans syndrome after redo lung transplantation was compared with the occurrence of bronchiolitis obliterans after primary transplantation. RESULTS: A 1-year survival of 50% was achieved after redo lung transplantation for acute graft failure and airway complications as well as after primary lung transplantation in patients with pretransplant ventilatory support. Retransplantation for bronchiolitis obliterans syndrome revealed superior 1- (78%) and 5-year (62%) survivals, which were not different from those of first-time lung transplant recipients. In addition, we found a similar incidence of bronchiolitis syndrome after retransplantation for BOS compared with its occurrence after primary lung transplantation. CONCLUSION: Redo lung transplantation for end-stage bronchiolitis obliterans syndrome leads to acceptable long-term outcome in selected patients. Future analyses of redo lung transplantation data should generally stratify bronchiolitis obliterans syndrome from other indications with higher mortality.
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The prospects of patients on the thoracic waiting list are governed by the chance of receiving an organ in time and by the outcome of the transplantation. The former probability is determined by a triad of disease severity, resource size and allocation rules. The aim of this study was to provide an objective description of the distributional effects of the thoracic allocation system in Eurotransplant. It appears that the interpretation of waiting-list outflow indicators is not straightforward and that it is difficult to assess the fairness of an organ allocation system in the framework of changing donor-organ availability. The timing of listing for heart transplantation can substantially be improved; whether this is also true for lung transplantation cannot be determined from the available data. Allocation schemes cannot solve the problem of organ shortage; a shift of attention toward collaboration with procurement professionals is needed.
Glycine reduces ischemia-reperfusion injury after experimental liver transplantation. We hypothesized that glycine might also protect right heart function in an isovolumic cardiac transplantation model. In six domestic donor pigs 150 ml of a 300 mmol L-glycine solution were administered intravenously. The hearts were then arrested with histidine-tryptophan-ketoglutarate solution. Animals without prior glycine infusion served as controls (n = 6). After 4 h of ischemia, hearts were transplanted into recipients. An isovolumic model was used in which the right ventricular (RV) volume was controlled in vivo using an intracavitary high-compliance balloon. After 1 and 2 h of reperfusion the RV balloon volume was gradually increased and the developed pressures were recorded (P(developed) = P(systolic) - P(diastolic)). Right ventricular failure was defined as a decrease in developed intracavitary pressure. Glycine hearts could be loaded with a significantly increased volume after 1 h (glycine: 53 +/- 13.7 ml vs. control: 32 +/- 11.7 ml; P = 0.015) and after 2 h (67 +/- 18.6 ml vs. 43 +/- 8.2 ml; P = 0.018). Maximal RV developed pressures were not significantly different between groups. Postischemic RV end-diastolic compliance was significantly higher in glycine-treated animals (P = 0.04). Glycine protects early postischemic RV compliance, but has no important influence on maximal developed pressures.
Inhibition of complement activation via human membrane-associated complement regulators is known to prevent hyperacute rejection in heart and kidney pig-to-primate transplantation. The protective effect of such strategies in pulmonary xenografts, however, seems to be insufficient. In an ex vivo perfusion, model lungs from donor pigs transgenic for human CD55 (n = 6) or human CD59 (n = 5) were perfused with fresh human blood and compared with nontransgenic organs (n = 6). In addition, a soluble complement component 1 esterase inhibitor (C1-Inh) was applied in h-CD55 transgenic lungs (n = 3). In the h-CD55 transgenic group, survival was prolonged (P < 0.05), quality and maximal time of oxygenation significantly improved and pulmonary vascular resistance reduced compared with the control group. There was a decreased sequestration of platelets, less parenchymal injury and reduced deposition of C(5b-9) in the h-CD55 transgenic group. Additional soluble complement inhibition (C1-Inh) did not prolong survival of h-CD55 transgenic lungs. Survival and pulmonary function in lungs expressing h-CD59 was not significantly different from parameters observed in nontransgenic lungs. In this ex vivo model of pig-to-primate lung transplantation, membrane-based complement inhibition resulted in significantly improved pulmonary function. However, minor histopathological injuries observed in these transgenic xenografts suggested only partial protection from pulmonary dysfunction by complement inhibition alone.
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