학술논문

Reduction of myocardial infarction by calpain inhibitors A-705239 and A-705253 in isolated perfused rabbit hearts
Document Type
research-article
Source
Biological Chemistry. 385(11):1077-1082
Subject
coronary perfusion
coronary occlusion
enzyme release
infarct size
left ventricular pressure
Highlight: Hiroshi Maeda – a life dedicated to research on infection, inflammation and cancer
Biochemistry
Molecular biology
Cellular biology
Language
English
ISSN
1437-4315
1431-6730
Abstract
Two novel calpain inhibitors (A-705239 and A-705253) were studied in isolated perfused rabbit hearts subjected to 60-min occlusion of the ramus interventricularis of the left coronary artery (below the origin of the first diagonal branch), followed by 120 min of reperfusion. The inhibitors were added to the perfusion fluid in various final concentrations from the beginning of the experiments before the coronary artery was blocked. Hemodynamic monitoring and biochemical analysis of perfusion fluid from the coronary outflow were carried out. Myocardial infarct size and the area at risk (transiently non-perfused myocardium) were determined from left ventricular slices after a special staining procedure with Evans blue and 2,3,5-triphenyltetrazolium chloride. The infarcted area (dead myocardium) was 77.9±2.3% of the area at risk in untreated controls (n=12). The infarct size was significantly reduced in the presence of both calpain inhibitors. The best effect was achieved with 10-8 M A-705253 (n=8), which reduced (p