Nicorandil improves myocardial high-energy phosphates in postinfarction porcine hearts.
1. Nicorandil is a potent vasodilator combining the effects of a nitrate with an ATP-sensitive potassium channel (K(ATP)) opener. Because the postinfarct remodelled heart has increased vulnerability to subendocardial hypoperfusion, it is possible that the vasodilator effects of nicorandil could cause transmural redistribution of blood flow away from the subendocardium. Alternatively, the K(ATP) channel opening effects of nicorandil could exert a beneficial effect on mitochondrial respiration. Consequently, the present study was performed to examine the effect of nicorandil on energy metabolism in the postinfarct heart. 2. Studies were performed in swine in which myocardial infarction produced by proximal left circumflex coronary artery ligation had resulted in left ventricular remodeling. [(31)P] nuclear magnetic resonance spectroscopy (MRS) was used to examine the myocardial energy supply/demand relationship across the left ventricular wall while the transmural distribution of blood flow was examined with radioactive microspheres. Data were obtained during baseline conditions and during infusion of nicorandil (100 microg, i.v., followed an infusion of 25 microg/kg per min). 3. Nicorandil caused coronary vasodilation with a preferential increase in subepicardial flow; however, subendocardial flow also increased significantly. Nicorandil had no significant effect on the rate-pressure product or myocardial oxygen consumption. The ratio of phosphocreatine (PCr)/ATP determined with MRS was abnormally depressed in remodelled hearts (2.01 +/- 0.11, 1.85 +/- 0.10 and 1.59 +/- 0.11 for subepicardium, midwall and subendocardium, respectively) compared with normal (2.22 +/- 0.11, 2.01 +/- 0.15 and 1.80 +/- 0.09, respectively). Nicorandil had no effect on the high-energy phosphate content of normal hearts. However, nicorandil increased the PCr/ATP ratio in the subendocardium of remodelled hearts from 1.59 +/- 0.11 to 1.87 +/- 0.10 (P < 0.05). 4. Although nicorandil caused modest redistribution of blood flow away from the subendocardium of the postinfarct left ventricle, this was associated with an increase of the PCr/ATP ratio towards normal. These results suggest that nicorandil exerts a beneficial effect on energy metabolism in the subendocardium of the postinfarct remodelled left ventricle.
Murakami
Yo
Y
The Fourth Department of Internal Medicine, Shimane Medical University, Izumo, Shimane, Japan.
Wu
Xiaoyun
X
Zhang
Jianyi
J
Ochiai
Koichi
K
Bache
Robert J
RJ
Shimada
Toshio
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D006439:Hemodynamics; D007773:Lactates / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D010101:Oxygen Consumption / Q000187:drug effects / Q000502:physiology; D010710:Phosphates / Q000378:metabolism*; D013552:Swine
D001786:Blood Glucose; D007773:Lactates; D010710:Phosphates; D020108:Nicorandil; D000255:Adenosine Triphosphate