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 pressure with oxygenated Tyrode solution. Ca paradox was induced by 10 min Ca free perfusion followed by 10 min Ca repletion. 10(-6) M d-sotalol was administered either during Ca depletion or during Ca repletion period. Electrical 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 majority of cardiomyocytes were irreversibly injured and profound dissociation of intercellular junctions was detected. Administration of d-sotalol during Ca free period preserved electrical activity and restored ventricular contraction accompanied by apparent protection of the ultrastructure, including intercellular connections. Uniform patterns of sarcomeres reflected synchronous contraction and protection of junctional couplings. In conclusion, d-sotalol attenuates Ca paradox injury. It seems that the protective effect of d-sotalol is most likely related to inhibition of potassium efflux antagonizing Na loading during Ca depletion period, as well as to attenuation of excess of [Ca2+]i via acceleration of sarcoplasmic Ca exchange during Ca repletion.
Tribulova
N
N
Institute for Heart Research, Slovak Academy of Sciences, Bratislava, Slovak Republic.
Sosner
I
I
Varon
D
D
Manoach
M
M
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002118:Calcium / Q000494:pharmacology / Q000502:physiology*; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000648:ultrastructure*; D026902:Potassium Channel Blockers; D013015:Sotalol / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D007552:Isotonic Solutions; D026902:Potassium Channel Blockers; C037692:Tyrode's solution; D013015:Sotalol; D002118:Calcium; D004837:Epinephrine