Comparative effects of nicorandil, nitroglycerin, nicotinic acid, and SG-86 on the metabolic status and functional recovery of the ischemic-reperfused myocardium.
The effects of nicorandil (SG-75), its major metabolite (SG-86), nitroglycerin, and nicotinic acid on myocardial segment shortening (% SS) and velocity of shortening (dL/dt, mm/s) were compared with those of a control group during 15 min of coronary occlusion followed by 3 h of reperfusion in anesthetized dogs. Piezoelectric crystals were used to measure % SS and dL/dt in regions perfused by the left anterior descending (LAD) and left circumflex (LC) coronary arteries. The radioactive microsphere technique was used to measure regional myocardial blood flow, and arterial and coronary sinus blood samples were obtained for the determination of glucose and free fatty acids. All drugs were administered intravenously 30 min before and throughout the occlusion period. Nicorandil (25 micrograms/kg/min) and nitroglycerin (3 micrograms/kg/min) produced nearly equivalent reductions in the heart rate-systolic pressure product. Nicotinic acid (0.3 mg/kg/min) and SG-86 (50 micrograms/kg/min) had no hemodynamic effects. Nicotinic acid reduced free fatty acid uptake during occlusion and at 30 min of reperfusion, whereas the other three agents had no major effects on substrate utilization. During occlusion, % SS in the ischemic region was severely depressed; collateral blood flow was similar in each series. However, during reperfusion, the nicorandil- and nicotinic acid-treated animals showed a marked improvement in % SS and dL/dt, as compared with those treated with saline (control), nitroglycerin, or SG-86. The mechanism(s) responsible for the beneficial actions of nicotinic acid and nicorandil in this model are unknown but may be partially related to the effect of nicotinic acid to reduce fatty acid uptake by the ischemic myocardium and the peripheral hemodynamic actions of nicorandil.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003327:Coronary Disease / Q000378:metabolism / Q000503:physiopathology*; D004285:Dogs; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology; D009536:Niacinamide / Q000031:analogs & derivatives / Q000494:pharmacology; D020108:Nicorandil; D005996:Nitroglycerin / Q000494:pharmacology; D010477:Perfusion; D014665:Vasodilator Agents / Q000494:pharmacology*
D005230:Fatty Acids, Nonesterified; D014665:Vasodilator Agents; D009536:Niacinamide; D020108:Nicorandil; D009525:Niacin; C030731:N-(2-hydroxyethyl)nicotinamide; D005996:Nitroglycerin; D005947:Glucose