Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart

The exact mechanism of mechano-electrical feed-back and stretch-induced arr hythmias is unknown, but the role of stretch-activated ion channels and spe cific calcium channels has been proposed. The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and th at these effects can be neutralized by stretch-activated channel block. We studied the interaction of acute ventricular dilatation and the stretch-act ivated channel blocker streptomycin and the specific calcium channel blocke r verapamil in an isolated retrogradely perfused rabbit heart model in whic h the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle. Acute ventricular dila tation led to a rate-dependent decrease in repolarization. The mean effecti ve refractory period (ERP) and monophasic action potential duration (MAP(90 )) for cycle lengths between 300 and 1,000 ms decreased from 174.2 +/- 9 ms and 178.9 +/- 7 ms to 161.6 +/- 11 ms and 169.7 +/- 5 ms, respectively. St reptomycin (80 muM) inhibited this stretch-related shortening of repolariza tion (ERP: 175.4 +/- 8 ms; MAP(90): 179.7 +/- 8 ms, p < 0.05) but had almos t no effect on already dilated ventricles. Counteraction of the observed el ectrophysiologic changes could only be achieved by increasing the streptomy cin concentration to 200 <mu>M. Streptomycin nearly completely suppressed s tretch-related ectopic ventricular complexes. In contrast, verapamil (1 muM ) had no effect on stretch-related changes in repolarization and stretch-in duced arrhythmias. The present study indirectly implicates stretch-activate d ion channels in the genesis of stretch-related changes in repolarization and arrhythmias. The electrophysiologic changes after ventricular dilatatio n to a degree that increases left ventricular pressure in a clinically rele vant range can be influenced by the stretch-activated channel blocker strep tomycin but not by specific calcium channel block. This may have clinically important implications for the development of new antiarrhythmic drugs.