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)
Ichihara
K
K
Department of Pharmacology, Asahikawa Medical College, Japan.
Abiko
Y
Y
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002354:Carteolol / Q000494:pharmacology; D004285:Dogs; D005260:Female; D005635:Fructosediphosphates / Q000378:metabolism; D005636:Fructosephosphates / Q000378:metabolism; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009248:Nadolol / Q000494:pharmacology; D010101:Oxygen Consumption; D011433:Propranolol / Q000494:pharmacology
D002121:Calcium Channel Blockers; D005635:Fructosediphosphates; D005636:Fructosephosphates; D005958:Glucosephosphates; D009248:Nadolol; D019298:Glucose-6-Phosphate; C027618:fructose-6-phosphate; D002354:Carteolol; D011433:Propranolol; C029063:fructose-1,6-diphosphate