Oxyfedrine and propranolol. A comparative experimental approach to protect myocardium against isoprenaline-induced myocardial necrosis.
Myocardial necrosis was produced in rats by isoprenaline (ISP) administration (85 mg X kg-1 s.c.) for two consecutive days. Rats sacrificed at 12, 24, 30, 36 and 48 h, respectively, after the last injection of ISP showed a marked increase in serum enzymes, viz. creatine phosphokinase (CPK), lactic dehydrogenase (LDH) and aspartate transaminase (AST) and tissue content of lactate. In addition, there was a significant reduction in the glycogen content of myocardium and the activity of enzyme phosphofructokinase (PFK) was changed in biphasic fashion, i.e. initial enhancement of activity was followed by a persistent fall. All these changes were present along with typical infarct-like necrosis as seen microscopically. Both oxyfedrine (OXF, 2, 4 and 8 mg X kg-1 i.m.) and propranolol (PROP, 1, 2 and 4 mg X kg-1 i.m.) administered for 5 days before and two days during ISP administration were effective in providing protection. However, with 8 mg X kg-1 dose of PROP sporadic high mortality was observed. Serum AST and CPK levels in OXF (4 and 8 mg X kg-1) and PROP (2 and 4 mg X kg-1) pretreated animals returned back to the range of controls. Unlike OXF, the LDH level in PROP pretreated rats, though reduced significantly, remained always higher than the control values. The beneficial effect of OXF on myocardial glycolytic flux was dose-dependent. 8 mg X kg-1 of OXF increased (31%) the glycogen content significantly (p less than 0.01) and the activity of enzyme PFK and tissue lactate content were brought back to normal. PROP did not exhibit dose-dependent reduction in the lactate content of the myocardium and it was never restored back to the range of control values.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D005260:Female; D006019:Glycolysis / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors*; D008297:Male; D009206:Myocardium / Q000473:pathology; D009336:Necrosis / Q000517:prevention & control; D010099:Oxyfedrine / Q000494:pharmacology*; D011427:Propiophenones / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D011427:Propiophenones; D011433:Propranolol; D010099:Oxyfedrine; D007545:Isoproterenol