Effectiveness of nicorandil in the preservation of myocardium stressed by transient ischemia and its influence on cardiac metabolism during coronary artery occlusion with subsequent reperfusion: a comparison with isosorbide dinitrate.
This study was designed to investigate the effects of nicorandil in comparison to isosorbide dinitrate (ISDN) on hemodynamics, on myocardial metabolism and on effectiveness in the preservation of ischemically stressed myocardium. Repeated ischemia (3 min) was produced in anaesthetized open-chest mongrel dogs by proximal, intermittent left anterior descending artery occlusion with subsequent reperfusion. In each experiment 2--3 control occlusions were compared to 2--3 occlusions under nicorandil or ISDN. Application of both nicorandil (0.64 mumol X kg-1 body weight, i.v.) and ISDN (1.27 mumol X kg-1 body weight, i.v.) led to a significant afterload reduction and to a decrease of the coronary vascular resistance. The efficiency of the compounds in the protection of ischemic myocardium was examined by quantification of oxygen-debt and oxygen-repayment in the occlusion and reperfusion periods. Compared to control, premedication with nicorandil led to a significant increase of oxygen-debt, whereas ISDN reduced it significantly. Oxygen-repayment remained unchanged. The influence of the drugs on the metabolism of glucose, lactate and free fatty acids (FFA) was examined under basic conditions, in ischemia and during reperfusion. For all substrates, extraction, extraction ratio and oxygen extraction ratio were calculated. Under basic conditions, glucose metabolism was significantly enhanced in both groups but FFA metabolism was inhibited only by ISDN. In ischemia, FFA metabolism was enhanced by nicorandil and depressed by ISDN.(ABSTRACT TRUNCATED AT 250 WORDS)
Korb
H
H
Hoeft
A
A
Hunneman
D H
DH
Schraeder
R
R
Wolpers
H G
HG
Hellige
G
G
D000818:Animals; D003327:Coronary Disease / Q000378:metabolism*; D003331:Coronary Vessels; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007548:Isosorbide Dinitrate / Q000494:pharmacology*; D007773:Lactates / Q000378:metabolism; D019344:Lactic Acid; D008026:Ligation; D009206:Myocardium / Q000378:metabolism*; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D010477:Perfusion
D005230:Fatty Acids, Nonesterified; D007773:Lactates; D009536:Niacinamide; D020108:Nicorandil; D019344:Lactic Acid; D007548:Isosorbide Dinitrate; D005947:Glucose