Electrophysiologic effects of exogenous phosphocreatine in cardiac tissue: potential antiarrhythmic actions.
The cellular electrophysiologic effects of exogenous phosphocreatine (PCr) were analyzed to ascertain its purported antiarrhythmic properties during myocardial ischemia and reperfusion. Transmembrane potentials were recorded from isolated guinea pig papillary muscles and Purkinje fibers studied in vitro. Under control, normoxic conditions, 10 mmol/L PCr significantly increased the action potential duration (measured at 90% of repolarization) in ventricular muscle by 14.6 +/- 3.3 msec and the effective refractory period by 11.5 +/- 3.8 msec (both p less than 0.01). Under ischemic-like conditions (hypoxia, lactic acidosis, elevated [K+]o, zero substrate) PCr had no effect. Phosphocreatinine, a related compound that is not a direct substrate in the creatine kinase reaction, acted similarly to PCr suggesting that alterations induced by PCr did not involve a change in the energy state of cells. However, PCr reduced free [Ca2+]o by nearly 20%, and its electrical effects under normoxic conditions could be largely reversed by a concomitant 20% increase in [Ca2+]o. In Purkinje fibers superfused with low [K+]o-Tyrode's solution to elicit conditions of Ca2+ overload, delayed afterdepolarizations and triggered responses were reversibly inhibited by PCr. These data suggest that the antiarrhythmic effects of PCr in situ may involve prolongation of the effective refractory period in nonischemic tissue or attenuation of membrane changes elicited by Ca2+ overload in ischemic cells. The mechanism by which PCr produces these effects may be related in part to changes in extracellular Ca2+ composition.
Rosenshtraukh
L V
LV
Institute of Experimental Cardiology, USSR Cardiology Research Center, Moscow.
Witt
R C
RC
Nance
P N
PN
Rozanski
G J
GJ
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000188:drug therapy*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D010210:Papillary Muscles / Q000187:drug effects* / Q000502:physiology; D010725:Phosphocreatine / Q000031:analogs & derivatives / Q000494:pharmacology*; D011690:Purkinje Fibers / Q000187:drug effects* / Q000502:physiology
D010725:Phosphocreatine; C025403:phosphocreatinine