The effects of two antianginal drugs,
nicorandil and
isosorbide dinitrate (ISDN), on metabolism and function of the ischemic myocardium were studied in a preparation of multiple
coronary occlusions in
barbital-anesthetized dogs. The preparation consisted of three 5 min occlusions of the left anterior descending coronary artery interspersed by 30 min of reperfusion. An equihypotensive dose of
nicorandil (7.5 micrograms/kg/min) or ISDN (12.5 micrograms/kg/min) was infused 15 min before and during the second occlusion period. Hemodynamics, myocardial segment shortening (%SS), tissue blood flow, and myocardial oxygen consumption were determined throughout. Uptake of
free fatty acids (FFA),
glucose, and
lactate were determined during control and ischemic periods. At the end of the final 30 min reperfusion period, biopsy samples of transmural tissue were taken for analysis of
phosphocreatine,
adenine nucleotides, and total tissue water content. No major hemodynamic changes were produced by either
drug except for a 5 to 10 mm Hg decrease in mean aortic pressure. Compared with untreated and ISDN-treated hearts, hearts of dogs treated with
nicorandil exhibited reversal of a significant increase in FFA uptake during recurrent
ischemia. This was accompanied by an attenuation of the increase in
oxygen extraction and CO2 production in the ischemic zone by
nicorandil, but not by ISDN.
Nicorandil, but not ISDN, improved %SS during reperfusion. Endocardial
ATP and total
adenine nucleotides were preserved in both
nicorandil- and ISDN-treated hearts. Tissue
edema was also attenuated by both compounds. Thus,
nicorandil improved both function and metabolism during recurrent
myocardial ischemia independent of a hemodynamic effect, whereas ISDN only attenuated the loss of
adenine nucleotides and increase in tissue water.