Role of cardiovascular and ionic changes in pathogenesis and prevention of isoprenaline-induced cardiac necrosis.
Blood pressure, heart rate, oxygen uptake, and blood values of PO2, PCO2, and pH were studied in unanesthetized rats for 8 hours. After a cardiotoxic dose of 20 mg/kg isoprenaline, s.c., blood pressure fell from 117 to 72 mm Hg, heart rate accelerated from 326 to 497 beats/minute, and cardiac work diminished by about 15%. Metabolic rate increased by about 80%, blood values of PO2 rose, and those of PCO2 fell somewhat, whereas blood pH dropped from 7.48 to 7.38, indicating metabolic acidosis. Propranolol (40 mg/kg, i.p.) and verapamil (50 mg/kg, i.p.), both of which almost completely prevented isoprenaline-induced cardiac necroses, inhibited the chronotropic and calorigenic actions of isoprenaline by about 50%. While propranolol inhibited the depressor effect of isoprenaline completely, verapamil enhanced it: blood pressure fell to 46 mm Hg. Isoprenaline-induced fall of blood pH was not prevented by either propranolol or verapamil. Decrease of blood pH and cardionecrotisation were enhanced when isoprenaline was given together with 4.8 g/kg ethanol, p.o. In conclusion, hemodynamic actions of isoprenaline, especially hypotension, seem to be nonessential for the production of cardiac necroses. Strong acidification can aggravate the cardiotoxicity of isoprenaline.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002245:Carbon Dioxide / Q000097:blood; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D006863:Hydrogen-Ion Concentration; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009336:Necrosis; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011433:Propranolol / Q000627:therapeutic use; D051381:Rats; D014700:Verapamil / Q000627:therapeutic use
D002245:Carbon Dioxide; D011433:Propranolol; D014700:Verapamil; D007545:Isoproterenol; D010100:Oxygen