Anti-inflammatory actions of aprotinin provide dose-dependent cardioprotection from reperfusion injury

Background and purpose: Myocardial injury following ischaemia and reperfusion has been attributed to activation and transmigration of polymorphonuclear leukocytes (PMNs) with release of mediators including oxygen-derived radicals and proteases causing damage. Experimental approach: We studied the serine protease inhibitor aprotinin in an in vivo rabbit model of 1 h of myocardial ischaemia followed by 3 h of reperfusion (MI+R). Aprotinin (10 000 Ukg−1) or its vehicle were injected 5 min prior to the start of reperfusion. Key results: Myocardial injury was significantly reduced with aprotinin treatment as indicated by a reduced necrotic area (11±2.7% necrosis as percentage of area at risk aft…

Aortenisthmusstenose bei Erwachsenen: operative Korrektur - mittel- und langfristige Ergebnisse

Fragestellung Ziel dieser retrospektiven Untersuchung war es, die Mittel- und Langzeitergebnisse der operativen Korrektur von Aortenisthmusstenosen (ISTHA) bei Erwachsenen zu erfassen. Patienten und Methodik Zwischen August 1985 und Januar 1999 wurden 20 Patienten (8 Frauen, 12 Manner) wegen ISTHA im Alter 19–60 Jahren (im Mittel 33 Jahre) operiert. Alle Patienten fielen klinisch durch Bluthochdruck der oberen Extremitaten auf (im Mittel 177/92 mmHg). Bei 9 Patienten von 16 (56%) handelte es sich um einen Zufallsbefund (bei 4 konnte dies nicht eruiert werden). Eine eingeschrankte praoperative Belastbarkeit wiesen 13 Patienten (65%) auf. Herzrhythmusstorungen zeigten sich bei 3 Patienten (15…

Magnetic resonance direct thrombus imaging for pre-operative assessment of acute thrombosis in chronic thromboembolic pulmonary hypertension

Aprotinin inhibits leukocyte–endothelial cell interactions after hemorrhage and reperfusion

Background. The serine protease inhibitor aprotinin has been successfully used to reduce blood loss in patients undergoing cardiac operations. We studied aprotinin for its ability to modulate leukocyte– endothelial cell interactions after ischemia and reperfusion. Methods. The effects of aprotinin on leukocyte– endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and immunohistochemical analysis. The inflammatory cascade (leukocyte rolling, firm adherence, and transmigration) was studied after thrombin stimulation and after hemorrhage and reperfusion. Results. Intravenous bolus administration of aprotinin treatment (20,000 U/kg) signifi…

Simvastatin Inhibits Inflammatory Properties ofStaphylococcus aureusα-Toxin

Background—Simvastatin, a 3-hydroxy-methylglutaryl coenzyme A reductase inhibitor, has been shown to lower serum cholesterol levels in clinical use. Moreover, statins exert beneficial effects in vascular diseases by inhibition of leukocyte rolling, adherence, and transmigration. The aim of this study was to determine if pretreatment with simvastatin attenuatesStaphylococcus aureusα-toxin–induced increase in leukocyte-endothelial interactions during exotoxemia.Methods and Results—The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation. Simvastatin (50 or 100 μg/kg) was administered 18 hours before the…

Cardioprotective effects of the serine protease inhibitor aprotinin after regional ischemia and reperfusion on the beating heart.

AbstractObjective: Early coronary reperfusion of the ischemic myocardium is a desired therapeutic goal to preserve myocardium. However, reperfusion itself contributes to an additional myocardial injury (ie, reperfusion injury), which has been attributed to neutrophil infiltration with subsequent release of proteases and oxygen-derived radicals. We studied the effects of the serine protease inhibitor aprotinin (Trasylol) on myocardial ischemia and reperfusion in a rat model. Methods: The effects of aprotinin (5000 and 20,000 U/kg) were examined in vivo in a rat model of regional myocardial ischemia (20 minutes) and long-term reperfusion (24 hours). Cardioprotecive effects were determined by …

Sodium/hydrogen exchange inhibition with cariporide reduces leukocyte adhesion via P-selectin suppression during inflammation

Background and purpose: The Na+/H+ exchange (NHE) inhibitor cariporide is known to ameliorate ischaemia/reperfusion (I/R) injury by reduction of cytosolic Ca2+ overload. Leukocyte activation and infiltration also mediates I/R injury but whether cariporide reduces I/R injury by affecting leukocyte activation is unknown. We studied the effect of cariporide on thrombin and I/R induced leukocyte activation and infiltration models and examined P-selectin expression as a potential mechanism for any identified effects. Experimental approach: An in vivo rat mesenteric microcirculation microscopy model was used with stimulation by thrombin (0.5 μ ml−1) superfusion or ischaemia (by haemorrhagic shock…

Neutrophil Adherence to Activated Saphenous Vein and Mammary Endothelium After Graft Preparation

Interaction of circulating leukocytes and vascular endothelium plays an important role in vasoconstriction, endothelial dysfunction, and vascular injury. Dilation procedures of grafts before coronary artery bypass graft surgery might lead to vascular injury and subsequent bypass graft disease.We analyzed in vitro the adherence of fluorescence-labeled polymorphonuclear neutrophils (PMNs) to endothelium of human saphenous vein grafts or internal mammary artery grafts after stimulation with thrombin (0.5 to 2 U/mL) or dilating procedures. Furthermore, we investigated endothelial function of prepared grafts.Thrombin stimulation resulted in a dose-dependent increase of PMN adherence to the endot…

The Fontan-Operation: From Intra- to Extracardiac Procedure

Purpose For treatment of univentricular heart, the Fontan operation has been established as the definitive palliation. The current controversy is mainly based on the high incidence of arrhythmias after an intra-atrial lateral tunnel Fontan operation. Methods From January 1995 until April 2002. 46 children underwent a Fontan-type operation with or without a small fenestration. In 33 patients (group I) an Intracardiac tunnel and in 13 patients (group II) an extracardiac conduit procedure was performed. Principal findings There was no perioperative mortality. All patients showed postoperative a significant increase of arterial oxygen saturation, from 76 to 86% after surgery with fenestration, …

Anti-inflammatory properties of simvastatin on leukocyte-endothelial cell interactions following hemorrhagic shock

Background Hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been shown to lower serum cholesterol levels. Recent studies reported that statins have vasculoprotective effects independent of their cholesterol-lowering properties. We studied simvastatin for its ability to modulate leukocyte-endothelial cell interactions under acute inflammation following hemorrhage and reperfusion. Methods The effects of simvastatin on leukocyte-endothelial cell interactions were observed by intravital microscopy in the rat mesenteric microcirculation and by immunohistochemical analyzes. Simvastatin (50 μg/kg or 100 μg/kg) was administrated intraperitoneally 18 h before study. Inf…