THE CONTRACTILE AND ELECTROPHYSIOLOGICAL EFFECTS OF ROLIPRAM IN GUINEA-PIG PAPILLARY-MUSCLES AND ISOLATED VENTRICULAR MYOCYTES

Isometric force, action potentials and in voltage-clamp I-si (second inward current) and its current voltage relation were recorded in papillary muscles from guinea-pigs and from guinea-pig isolated ventricular myocytes (35-37 degrees C, 0.5-1 Hz). Rolipram (1-100 mu M) had no significant effect on peak isometric twitch. The rate of rise of force and time to peak tension (TPT) was likewise unaffected. Time to half relaxation (THR) was increased in a dose-dependent manner and at 30 mu M THR was prolonged by 25.3+/-6% (n = 10, P < 0.001). The effect of 30 mu M rolipram on isometric force was frequency dependent. At 0.25 Hz peak force was increased by 6.3+/-3.1% (n = 7, P < 0.05). At 2 Hz rolipram exhibited a negative inotropic effect of 9.8+/-3.3% (n = 5, P < 0.02). Action potential duration at 90% repolarization was prolonged by 13+/-6 ms (n = 7, P < 0.05), and there was usually no effect on resting potential or action potential amplitude. Sometimes, however, a depressed plateau was recorded. Rolipram was without effect on I-st and its current-voltage relations. Time to full mechanical restitution after a test interval was not changed but the shape of the restitution curve was altered. The restitution process was much slower in the presence of rolipram. Hence, peak force was lower at test intervals shorter than 800 ms. Likewise, the shape of the curve relating postextrasystolic potentiation to test interval was altered by rolipram. The interval required for maximum potentiation was increased by rolipram and did not significantly affect the recirculation fraction of activator calcium.