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.
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.