Hemodynamic effects of grisorixin, a monocarboxylic ionophore

The cardiovascular effects of grisorixin, a monocarboxylic ionophore, were studied in anesthetized dogs. At low doses, up to 60 micrograms/kg, grisorixin showed potent coronary vasodilator properties without marked effects on other cardiac parameters. The maximum increase in CBF was observed with the 60 micrograms/kg dose (+390%). With higher doses (125-500 micrograms/kg), the coronary vasodilation was more persistent and concomitant with strong inotropic and hypertensive effects. Pretreatment with a beta-blocking agent (propranolol 2 mg/kg) partly reduced the grisorixin-induced effects. The increase in CBF was lowered in the dogs receiving 60 micrograms/kg and shortened in those receiving 500 micrograms/kg while the rise in contractility was considerably reduced but not abolished; the hypertensive effect was almost not affected by pretreatment with propranolol. In no case was the myocardial oxygen consumption increased in proportion to cardiac work. It is suggested that like other ionophores such as monensin, grisorixin acts partly through a release of catecholamines but also by a nonadrenergic mechanism involving modifications in intra- and extracellular ionic concentrations.