Attenuation of Ca paradox injury in guinea pig heart by K+ channel blocker, d-sotalol

D-sotalol was shown to prevent Ca overload and intermyocyte uncoupling. The aim of this study was to investigate the effect of d-sotalol in Ca paradox conditions. Guinea pig hearts were perfused at 37 degrees C and constant p ressure with oxygenated Tyrode solution. Ca paradox was induced by 10 min C a free perfusion followed by 10 min Ca repletion. 10(-6) M d-sotalol was ad ministered either during Ca depletion or during Ca repletion period. Electr ical activity and ventricular contraction were simultaneously recorded and subcellular alterations were analysed. The contraction terminated in 5 min of Ca free perfusion and electrical activity disappeared within 5 min of Ca repletion. Nonuniform injury of myocardial tissue was observed. The majori ty of cardiomyocytes were irreversibly injured and profound dissociation of intercellular junctions was detected. Administration of d-sotalol during C a free period preserved electrical activity and restored ventricular contra ction accompanied by apparent protection of the ultrastructure, including i ntercellular connections. Uniform patterns of sarcomeres reflected synchron ous contraction and protection of junctional couplings. In conclusion, d-so talol attenuates Ca paradox injury. It seems that the protective effect of d-sotalol is most likely related to inhibition of potassium efflux antagoni zing Na loading during Ca depletion period, as well as to attenuation of ex cess of [Ca2+](i) via acceleration of sarcoplasmic Ca exchange during Ca re pletion.