Wolfgang Harringer
Harvard University
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Circulation | 2000
Bernhard Schieffer; Elisabeth Schieffer; Denise Hilfiker-Kleiner; Andres Hilfiker; Petri T. Kovanen; Maija Kaartinen; Jörg Nussberger; Wolfgang Harringer; Helmut Drexler
BACKGROUND Patients with an activated renin-angiotensin system (RAS) or genetic alterations of the RAS are at increased risk of myocardial infarction (MI). Administration of ACE inhibitors reduces the risk of MI, and acute coronary syndromes are associated with increased interleukin 6 (IL-6) serum levels. Accordingly, the present study evaluated the expression of angiotensin II (Ang II) in human coronary atherosclerotic plaques and its influence on IL-6 expression in patients with coronary artery disease. METHODS AND RESULTS Immunohistochemical colocalization of Ang II, ACE, Ang II type 1 (AT(1)) receptor, and IL-6 was examined in coronary arteries from patients with ischemic or dilated cardiomyopathy undergoing heart transplantation (n=12), in atherectomy samples from patients with unstable angina (culprit lesion; n=8), and in ruptured coronary arteries from patients who died of MI (n=13). Synthesis and release of IL-6 was investigated in smooth muscle cells and macrophages after Ang II stimulation. Colocalization of ACE, Ang II, AT(1) receptor, and IL-6 with CD68-positive macrophages was observed at the shoulder region of coronary atherosclerotic plaques and in atherectomy tissue of patients with unstable angina. Ang II was identified in close proximity to the presumed rupture site of human coronary arteries in acute MI. Ang II induced synthesis and release of IL-6 shortly after stimulation in vitro in macrophages and rat smooth muscle cells. CONCLUSIONS Ang II, AT(1) receptor, and ACE are expressed at strategic sites of human atherosclerotic coronary arteries, suggesting that Ang II is produced primarily by ACE within coronary plaques. The observation that Ang II induces IL-6 and their colocalization with the AT(1) receptor and ACE is consistent with the notion that the RAS may contribute to inflammatory processes within the vascular wall and to the development of acute coronary syndromes.
The New England Journal of Medicine | 1991
Carlos Fernandez-del Castillo; Wolfgang Harringer; Andrew L. Warshaw; Gus J. Vlahakes; Greg Koski; Alan M. Zaslavsky; David W. Rattner
BACKGROUND Pancreatitis is a known complication of cardiac surgery with cardiopulmonary bypass. Although ischemia is believed to be a factor, the cause of pancreatitis after cardiopulmonary bypass remains unknown. METHODS We prospectively studied 300 consecutive patients undergoing cardiac surgery with cardiopulmonary bypass. Serum amylase, pancreatic isoamylase, and serum lipase were measured on postoperative days 1,2,3,7, and 10. Pancreatic cellular injury was defined as the presence of hyperamylasemia (greater than 123 U per liter) with an increase in either the serum level of lipase (greater than 24 U per liter) or the peak level of pancreatic isoamylase. Trypsinogen-activation peptides, which indicate intrapancreatic enzyme activation, were measured in the urine of the last 101 patients studied. RESULTS Evidence of pancreatic cellular injury was detected in 80 patients (27 percent), of whom 23 had associated abdominal signs or symptoms and 3 had severe pancreatitis (2 with pancreatic abscess and 1 with necrotizing hemorrhagic pancreatitis). Two of 19 postoperative deaths were secondary to pancreatitis. In multivariate analyses, the development of pancreatic cellular injury was significantly associated with preoperative renal insufficiency, valve surgery, postoperative hypotension, and perioperative administration of calcium chloride. The administration of more than 800 mg of calcium chloride per square meter of body-surface area was an independent predictor of pancreatic cellular injury, and the increase in risk was dose-related. No differences were found in the level of trypsinogen-activation peptides between patients who had pancreatic cellular injury and those who did not. CONCLUSIONS Pancreatic cellular injury, as indicated by hyperamylasemia of pancreatic origin, is common after cardiac surgery. The administration of large doses of calcium chloride is an independent predictor of pancreatic cellular injury and may be a cause of it.
The Journal of Thoracic and Cardiovascular Surgery | 1994
John D. Mitchell; Raymond Lee; George T. Hodakowski; Kazou Neya; Wolfgang Harringer; C. Robert Valeri; Gus J. Vlahakes
Postoperative pericardial adhesions complicate reoperative cardiac procedures. Topical application of solutions containing hyaluronic acid have been shown to reduce adhesions after abdominal and orthopedic surgery. The mechanism by which hyaluronic acid solutions prevent adhesion formation is unknown but may be due to a cytoprotective effect on mesothelial surfaces, which would limit intraoperative injury. In this study, we tested the efficacy and safety of hyaluronic acid coating solutions for the prevention of postoperative intrapericardial adhesion formation. Eighteen mongrel dogs underwent median sternotomy and pericardiotomy followed by a standardized 2-hour protocol of forced warm air desiccation and abrasion of the pericardial and epicardial surfaces. Group 1 (n = 6) served as untreated control animals. Group 2 (n = 6) received topical administration of 0.4% hyaluronic acid in phosphate-buffered saline solution at the time of pericardiotomy, at 20-minute intervals during the desiccation/abrasion protocol, and at pericardial closure. The total test dose was less than 1% of the circulating blood volume. Group 3 (n = 6) served as a vehicle control, receiving phosphate-buffered saline solution as a topical agent in a fashion identical to that used in group 2. At resternotomy 8 weeks after the initial operation, the intrapericardial adhesions were graded on a 0 to 4 severity scale at seven different areas covering the ventricular, atrial, and great vessel surfaces. In both the untreated control (group 1, mean score 3.2 +/- 0.4) and vehicle control (group 3, mean score 3.3 +/- 0.2) animals, dense adhesions were encountered. In contrast, animals treated with the hyaluronic acid solution (group 2, mean score 0.8 +/- 0.3) characteristically had no adhesions or filmy, transparent adhesions graded significantly less severe than either the untreated control (group 2 versus group 1, p < 0.001) or vehicle control (group 2 versus group 3, p < 0.001) animals. In separate experiments, six baboons were infused with 0.4% hyaluronic acid in phosphate-buffered saline solution in volumes equivalent to 2.5%, 5%, and 10% of the measured circulating blood volume. The 2.5% and 5% infusions had no effect on the parameters measured; infusion of the 10% volume produced transient hemodynamic, coagulation, and gas exchange abnormalities. Hyaluronic acid solutions are efficacious in the prevention of pericardial adhesions in this model, and they appear safe in doses five times the amount needed to prevent adhesions. Further studies investigating the mechanism by which these solutions prevent adhesions, their optimal dose and method of application, and documentation of their safe use in humans are warranted.
European Journal of Cardio-Thoracic Surgery | 1992
Wolfgang Harringer; George T. Hodakowski; Tracy Svizzero; Edward E. Jacobs; Gus J. Vlahakes; T. Treasure
The capability of stroma-free hemoglobin solutions to act as a plasma expander with oxygen and carbon dioxide transport properties has encouraged the idea of their possible use in settings of massive blood loss. Using a canine hemorrhagic shock model (systolic arterial pressure < or = 50 torr for 60 min), we evaluated the efficacy of an ultra-pure stroma-free bovine hemoglobin solution (PBHg) as a resuscitation fluid in hypovolemic and acidotic animals, using homologous blood (PRBC) and 10% human serum albumin (HSA) as control solutions. Following volume replacement, dogs were studied for 2 h under anesthesia and for 4 h subsequently while awake. Resuscitation with PBHg (30 +/- 3 ml/kg) was able to restore stable hemodynamics and correct acidosis to an extent comparable to that in animals treated with PRBC. Additionally, oxygen transport was maintained at a higher level than that in dogs treated with HSA. Administration of PBHg in this shock model revealed no significant cardiopulmonary toxicity or adverse effects. These short-term results suggest that PBHg may be useful for effective resuscitation after major blood loss.
The Journal of Thoracic and Cardiovascular Surgery | 2009
John D. Puskas; Michael E. Halkos; Husam H. Balkhy; Michael P. Caskey; Mark W. Connolly; John Crouch; Anno Diegeler; Jan Gummert; Wolfgang Harringer; Valavanur A. Subramanian; Francis Sutter; Klaus Matschke
OBJECTIVE During coronary surgery, proximal vein graft anastomoses have been performed by using an aortic partial occlusion clamp to allow for a hand-sewn anastomosis. The purpose of this multicenter, prospective, randomized trial was to evaluate the efficacy of the PAS-Port device (Cardica, Inc, Redwood City, Calif), which allows an automated proximal anastomosis to be performed without aortic clamping. METHODS Between June 22, 2006, and March 22, 2007, 220 patients requiring coronary artery bypass grafting with at least 2 vein grafts were enrolled. Within each patient, 1 graft was randomly assigned to receive a PAS-Port device, and the other was assigned to receive a hand-sewn anastomosis to the ascending aorta. The primary end point was angiographic patency (<50% stenosis) 9 months after surgical intervention. Secondary end points included average time to complete each anastomosis and 9-month freedom from major adverse cardiac events. RESULTS One hundred eighty-three patients received matched grafts that were angiographically assessed at 9 months. The 9-month graft patency was 82.0% (150/183) for hand-sewn and 80.3% (147/183) for PAS-Port grafts. The patency rate of PAS-Port anastomoses was statistically noninferior to that of hand-sewn anastomoses (95% lower confidence limit for difference, -7.95%). The freedom from major adverse cardiac events at 9 months was 97.7% for PAS-Port (95% confidence interval, 94.5%-99.0%) and 98.2% for hand-sewn (95% confidence interval, 95.1%-99.3%) grafts. The PAS-port device was associated with a 4.6 +/- 3.9-minute reduction in anastomotic time compared with that seen with a hand-sewn anastomosis (P < .001). CONCLUSIONS The PAS-Port proximal anastomotic device produces an effective anastomosis with a 9-month patency rate that is comparable with that of a hand-sewn anastomosis. It allows for construction of a proximal anastomosis without aortic clamping and requires less time than a hand-sewn anastomosis.
European Journal of Cardio-Thoracic Surgery | 1994
Christoph Gross; Wolfgang Harringer; Rudolf Mair; Gerhard Wimmer-Greinecker; Uwe Klima; Peter Brücke
Between February 1982 and December 1992 we operated on five patients (three men, two women; aged 40 to 70 years) with mycotic aneurysms of the thoracic aorta. One patient had an aneurysm of the ascending aorta, once the aortic arch and in three cases the descending thoracic aorta were involved. In four of the five patients, excision of the aneurysm and in situ reconstruction of the aorta with a Dacron graft was performed, one patient required a Dacron graft repair and aortic valve replacement. We employed deep hypothermia with circulatory arrest (2), extracorporeal circulation (1), an axillofemoral shunt (1) and a centrifugal pump (1) for cerebral and spinal cord protection. One patient died 4 months postoperatively, the other four patients were without recurrent graft infection and are free of symptoms between 20 months and 5 years postoperatively.
The Journal of Thoracic and Cardiovascular Surgery | 1995
Martin Strüber; Joachim Cremer; Wolfgang Harringer; Stephan W. Hirt; Angelika Costard-Jäckle; Axel Haverich
Reperfusion injury is one of the major causes of early morbidity and mortality after lung transplantation. Features of thi s syndrome are pulmonary edema, reduction of compliance, and impaired gas exchange, and these occur in about 20% of all lung transplant recipients. Usual treatment includes prolonged mechanical ventilation with elevated positive end-expiratory airway pressure (PEEP), enhanced mean airway pressure with high oxygen content (Fio2), and, in severe cases, inverse ratio ventilation and extracorporeal membrane oxygenation. We report on the successful treatment with nebulized synthetic surfactant (Exosurf; Wellcome, Burgwedel, Germany) of a patient in whom reperfusion injury developed 5 hours after right lung transplantation. Right lung transplantation was done in a 26-year-old woman who had sarcoidosis with terminal interstitial lung disease and recurrent failure of the right side of the heart. The patient had been dependent on continuous oxygen insufllation for 30 months before transplantation. Pulmonary hypertension was present with a mean pulmonary artery pressure of 50 mm Hg.
European Journal of Cardio-Thoracic Surgery | 2000
Ulrich Franke; K Wiebe; Wolfgang Harringer; Thekla Franke; Thorsten Wittwer; Thorsten Wahlers; Axel Haverich
Objective: Patients with primary pulmonary hypertension (PPHT) have a worse natural outcome compared with those with secondary pulmonary hypertension in Eisenmenger’s syndrome (ES) and chronic pulmonary embolism (CPE). Lung transplantation (SLTx, DLTx, HLTx) still remains the only therapeutical option for patients with this type of endstage lung disease. Methods: From 1988 to 1998, 63 patients underwent lung transplantation for PPHT (na 29, 9 m, 20 f, 2 SLTx, 14 DLTx, 13 HLTx), ES (na 29, 13 m, 16 f, 2 SLTx, 3 DLTx, 24 HLTx) or CPE (na 5, 2 m, 3 f, 1 SLTx, 2 DLTx, 2 HLTx). Groups were comparable for NYHA functional class, preoperative pulmonary arterial pressure, recipient and donor age, ischemic time, necessity and duration of cardiopulmonary bypass and cross-match. Results: The 1-, 3- and 5-year survival was 52, 40 and 35% for the PPHT-group, 83, 78 and 74% for the ES-group and 80, 60 and 60% for the CPE-group, respectively (Pa 0:026, Pa 0:033, Pa 0:082 for 1-, 3- and 5-year survival). Patients following DLTx showed a lower 1-year survival rate as compared with patients after HLTx both in PPHT patients (36 vs. 62%, Pa 0:091) and in ES patients (67 vs. 83%, Pa 0:213). The incidence of bronchiolitis obliterans syndrome was 29% at 1 year and 45% at 3 years for the PPHT-group vs. 17 and 65% for the ES-group (n.s. in between groups). Excluding postoperative ventilation time (PPHT-group: 26.8 ^ 24.0 days vs. ES-group: 16.1 ^ 30.8 days, Pa 0:011) and a higher incidence of infectious causes of death (PPHT-group na 8 vs. ES-group na 1, Pa 0:017) groups were comparable with regard to their postoperative courses. Conclusions: It is concluded, that predominantly the underlying primary disease influences graft survival after lung transplantation in patients with pulmonary hypertension compared with all other patient and procedure dependent factors. Lung transplantation in patients with PPHT requires further investigations to achieve results comparable with other indications. q 2000 Elsevier Science B.V. All rights reserved.
European Journal of Cardio-Thoracic Surgery | 2010
Aschraf El-Essawi; Tomas Hajek; Jirji Skorpil; Andreas Böning; František Sabol; Harald Hausmann; Yuri Ostrovsky; Wolfgang Harringer
OBJECTIVE Minimised perfusion circuits (MPCs) are expected to reduce the side effects of conventional cardiopulmonary bypass (CCPB); however, conclusive data from sufficiently powered clinical trials are lacking. The purpose of this study was to evaluate the safety and efficacy of the ROCsafeRX minimised perfusion circuit. METHODS A randomised, controlled, multicentre clinical trial comparing both perfusion circuits in patients subjected to elective coronary artery bypass and/or aortic valve replacement is described. The primary end points of safety, defined as procedure success without device-related complications, and secondary end point of efficacy, including reduction of transfusion requirement and incidence of atrial fibrillation, are analysed. RESULTS To date, 291 patients have been enrolled and randomised (146 MPC vs 145 CCPB). With the exception of a significantly higher male population in the MPC group (83.6% vs 71.0%, p=0.01), both groups were well matched for demographic data and type of surgery. There were no device-related complications but a hard-shell reservoir had to be integrated in one MPC because of a tear in the right atrium that was managed uneventfully. Total transfusion requirement (329+/-599 ml vs 783+/-1638 ml, p < or = 0.001) and erythrocyte transfusion (181+/-341 ml vs 434+/-798 ml, p < or = 0.001) were significantly reduced in the MPC group. The incidence of atrial fibrillation was significantly lower in the MPC group (7.1% vs 19.5%, p < or = 0.01), while freedom of major adverse events showed no significant difference. CONCLUSIONS Lack of device-related complications combined with a significant reduction in postoperative atrial fibrillation and transfusion requirements have shown the ROCsafeRX MPC to be both safe and efficient for large-scale use in cardiac patients. Additional data are expected to confirm these initial findings.
Perfusion | 2011
Aschraf El-Essawi; T Hajek; J Skorpil; Andreas Böning; F Sabol; Y Ostrovsky; H Hausmann; Wolfgang Harringer
Introduction: Minimized perfusion circuits (MPCs), although aiming at minimizing the adverse effects of cardiopulmonary bypass, have not yet gained popularity. This can be attributed to concerns regarding their safety, as well as lack of sufficient evidence of their benefit. Methods: Described is a randomized, multicentre study comparing the MPC - ROCsafeRX to standard cardiopulmonary bypass in patients undergoing elective coronary artery bypass grafting and/ or aortic valve replacement. Results: Five hundred patients were included in the study (252 randomized to the ROCsafeRX group and 248 to standard cardiopulmonary bypass). Both groups were well matched for demographic characteristics and type of surgery. No operative mortality and no device-related complications were encountered. Transfusion requirement (333 ± 603 vs. 587 ± 1010 ml; p=0.001), incidence of atrial fibrillation (16.3% vs. 24.2%; p=0.03) and the incidence of major adverse events (9.1% vs. 16.5%; p=0.02) were all in favour of the MPC group. Conclusion: These results confirm both the safety and efficacy of the ROCsafeRX MPC for a large variety of cardiac patients. Minimized perfusion circuits should, therefore, play a greater role in daily practice so that as many patients as possible can benefit from their advantages.