Effects of trifluoperazine and chlorpromazine on calcium-repleted injury in isolated ventricle strips.
We observed changes in the performance of isolated right ventricle strips taken from rats when calcium was repleted following various periods of calcium depletion in order to study certain phenomena, such as the calcium paradox, in this preparation. Furthermore, to assess the possible role of calmodulin in this myocardial damage, the effects of known calmodulin inhibitors such as trifluoperazine and chlorpromazine on the contractility and resting tension were studied by means of the calcium repletion after a calcium-depleted period of 12 min. The temperature was kept at 37 degrees C, and the muscle strips were stimulated electrically at a rate of 0.25 Hz. When there was a calcium-depleted period of longer than 8 min, a marked increase in resting tension was observed and reached maximum at 2 to 4 min. The recovery of peak developed tension and peak positive or negative dT/dt worsened as the duration of the calcium depletion was longer. These findings indicate the massive intracellular calcium influx by the calcium reintroduction and the myocardial damage induced by the calcium overload as observed in isolated whole hearts. Treatment with trifluoperazine (1-5 microM) and chlorpromazine (1-5 microM) did not inhibit a rise in resting tension significantly after the calcium repletion, except for 5 microM of both drugs at 6 min. Trifluoperazine significantly improved the recovery of the contractility (developed tension and dT/dt), whereas the protective effect of chlorpromazine was not obtained. These results suggest that the depression of calmodulin activity is beneficial in the prevention of myocardial damage produced by calcium repletion, although there is a difference in the effect of the calmodulin inhibitors, trifluoperazine and chlorpromazine.
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D002746:Chlorpromazine / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014268:Trifluoperazine / Q000494:pharmacology*
D002147:Calmodulin; D014268:Trifluoperazine; D002118:Calcium; D002746:Chlorpromazine