Cardiac metabolism as an indicator of oxygen supply/demand ratio

We evaluated the anti-ischemic effect of drugs by using the inhibition of glycolytic flux at the level of the phosphofructokinase (PFK) reaction, caused by ischemia, as an indicator of the oxygen supply/demand ratio in the ischemic myocardium. Ischemia was induced by ligating the left anterior descending coronary artery in the open-chest dog. After 3 min of coronary ligation, the ischemic myocardium was removed. The endocardial portion of the myocardial sample was used to determine the levels of glucose-6-phosphate (G6P), fructose-6-phosphate (F6P) and fructose-1,6-diphosphate (FDP), and the ratio of [( G6P] + [F6P])/[FDP] was calculated in order to assess the rate of glycolytic flux at the PFK stage. Either saline or drug (propranolol, 1 mg/kg; carteolol, 100 micrograms/kg; nadolol, 1 mg/kg; nifedipine, 10 micrograms/kg; diltiazem, 100 micrograms/kg; verapamil, 100 micrograms/kg; and flunarizine, 1 mg/kg) was injected intravenously 5 min before coronary ligation. In the saline-treated heart, ischemia increased the levels of G6P and F6P, whereas it decreased the level of FDP. The ratio of ([G6P] + [F6P])/[FDP] was increased by ischemia from 2.2 to 23.6, suggesting the inhibition of glycolytic flux at the level of the PFK reaction. In the drug-treated heart, ischemia increased the levels of G6P and F6P, but the increases were smaller than those in the saline-treated heart. Pretreatment with propranolol, nadolol, diltiazem, verapamil, flunarizine attenuated the increase in the ratio of ([G6P] + [F6P])/[FDP] caused by ischemia.(ABSTRACT TRUNCATED AT 250 WORDS)