Hemodynamic effects of a potassium ionophore, lonomycin A

Lonomycin A, an ionophorous antibiotic, exhibits a high transport rate for monovalent cations, especially potassium. The cardiovascular actions of lonomycin A were studied in anesthetized dogs. Lonomycin A administered intravenously at 30 micrograms/kg increased coronary blood flow slightly with relatively small alterations in other hemodynamic parameters. After 100 micrograms/kg, a slight and transient fall followed by an increase in blood pressure was observed. Coronary blood flow, cardiac output, left ventricular pressure, max dP/dt, and isometric ventricular segmental tension increased. Arterial venous O2 difference and total peripheral vescular resistance decreased. Above 300 micrograms/kg, dramatic alterations were produced in almost all hemodynamic parameters, and total peripheral vascular resistance was increased. Lonomycin A-induced positive inotropic action was partly inhibited by pretreatment with pindolol, however gradual shortening of the ventricular wall length was still observed. A positive chronotropic action induced by lonomycin A was inhibited by pindolol pretreatment in vivo. On the other hand, lonomycin A elicited a negative chronotropic effects in the isolated guinea-pig right atrium, concomitantly increasing resting tension. These results suggest that lonomycin A alone produces peripheral vascular dilation and effects cardiac functions, which are in turn modified by lonomycin A-induced cathecholamine release from nerve terminals.