The effect of 2-(2,5-dimethoxyphenylmethyl)-3-(2-dimethylaminoethyl)- 6-isopropoxy-4(3H)-quinazolinone hydrochloride (MCI-176), a
calcium antagonist, on ischemic myocardial metabolism was studied in dog hearts subjected to an occlusion of the left anterior descending coronary artery (LAD) for 3 or 30 min.
MCI-176 (0.03 or 0.1 mg/kg), when injected i.v. 5 min before occlusion, increased coronary blood flow and decreased systemic aortic pressure. When the LAD was ligated, the levels of
creatine phosphate,
ATP, total
adenine nucleotides and energy change potential decreased in the ischemic myocardium. Three minutes after
ischemia,
MCI-176 (0.1 mg/kg) significantly (P less than 0.05) diminished these impairments of energy metabolism. Even 30 min after
ischemia, pretreatment with
MCI-176 tended to lessen the depletion of
ATP and total
adenine nucleotides, although these effects were not statistically significant.
Myocardial ischemia produced a breakdown of
glycogen, an accumulation of
lactate, and an inhibition of glycolytic flux through
phosphofructokinase reaction.
MCI-176 (0.1 mg/kg) significantly (P less than 0.05) reduced these alterations of carbohydrate metabolism after 3 min of
ischemia. These results suggest that pretreatment with
MCI-176 reduces the impairments of myocardial energy and carbohydrate metabolism in ischemic dog hearts, suggesting that the
drug is capable of improving the imbalance between
oxygen supply and
oxygen demand in the ischemic myocardium.