caa a22 4500 477112668 CHVBK 20180405111614.0 cr unu---uuuuu 170330e19961101xx s 000 0 eng 10.1007/BF01747187 doi (NATIONALLICENCE)springer-10.1007/BF01747187 The Protective effect of d -sotalol against hypoxia-induced myocardial uncoupling [Elektronische Daten] [Mordechai Manoach, Narcis Tribulova, Issei Imanaga] Summary: The effects ofd-sotalol on intercellular electrical coupling and ultrastructure under hypoxic conditions were investigated in myocardial samples from eight young (1-2 months) and four older (10-12 months) guinea pigs. A right ventricular muscle strip was kept simultaneously in two divided chambers and superfused with normoxic and/or hypoxic (97% N2+ 3% CO2) Krebs solution. Hypoxia caused shortening of action potential duration (APD) and electrical cellto-cell uncoupling. If the uncoupling appeared after short-term hypoxia (less than 30 min), administration of 3.10−7M ofd-sotalol to the hypoxic perfusate led to a recovery of electrical coupling. Transmission electron microscopy revealed moderate reversible ultrastructural alterations of the cardiomyocytes. No apparent changes in intercellular junctions were observed. The recoupling effect of sotalol decreased with the time of hypoxia as the ultrastructural damage progressed. After prolonged hypoxia (more than 30min), cardiomyocytes were markedly injured, intercellular junctions were severely affected, and gap junctions occurred less frequently. In these cases, administration ofd-sotalol caused only transient recoupling. After 1h of hypoxia, no recoupling was observed. Pretreatment withd-sotalol prevented hypoxia-induced electrical uncoupling and markedly attenuated ultrastructural damage, although shortening of APD still persisted. Our results indicate that the cardioprotective effect ofd-sotalol on electrical intercellular coupling is closely associated with sotalol-induced prevention of the ultrastructural damage. Considering previous results, we suggest that this protective effect ofd-sotalol may be related to its ability to increase intracellular cyclic adenosine monophosphate and, thereby, to decrease cytosolic free Ca. These effects can explain the antiarrhythmic and defibrillating properties ofd-sotalol. Springer-Verlag, 1996 Myocardium nationallicence Hypoxia nationallicence d -Sotalol nationallicence Intercellular uncoupling nationallicence Protection of intercellular coupling nationallicence Ultrastructural examination nationallicence Manoach Mordechai Department of Physiology, Tel-Aviv University, Medical School, 69978, Tel-Aviv, Israel aut Tribulova Narcis Department of Morphology, Institute of Heart Research Bratislava, Slovak Republic aut Imanaga Issei Department of Physiology, Fukuoka Medical School, Fukuoka, Japan aut Heart and Vessels Springer-Verlag 11/6(1996-11-01), 281-288 0910-8327 11:6<281 1996 11 380 https://doi.org/10.1007/BF01747187 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01747187 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Manoach Mordechai Department of Physiology, Tel-Aviv University, Medical School, 69978, Tel-Aviv, Israel aut NATIONALLICENCE 700 1- Tribulova Narcis Department of Morphology, Institute of Heart Research Bratislava, Slovak Republic aut NATIONALLICENCE 700 1- Imanaga Issei Department of Physiology, Fukuoka Medical School, Fukuoka, Japan aut NATIONALLICENCE 773 0- Heart and Vessels Springer-Verlag 11/6(1996-11-01), 281-288 0910-8327 11:6<281 1996 11 380 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer