Inhibition by theophylline of the early component of canine ventricular contraction

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Abstract
Changes in mechanical characteristics of the isolated canine ventricular muscle were investigated during interaction of isoproterenol with theophylline or caffeine. An early and a late component with time to peak tension of 80 and 150 ms, respectively, were differentiated in a single contraction of the muscle stimulated at 0.5 Hz at 37.degree. C during the interaction of isoproterenol and theophylline, or isoproterenol and caffeine. Isoproterenol preferentially increased the early component and slightly affected the late one. Theophylline or caffeine elevated the early component less than the late one. In the presence of theophylline + isoproterenol or caffeine + isoproterenol the peak tension was achieved by a late component; the increase in the early one induced by isoproterenol in 3 .times. 10-7 M and higher was depressed. During the interaction the rate of twitch relaxation was accelerated further rather than depressed. Changes in action potential indicate that the Ca influx via the myocardial cell membrane during depolarization was increased: the peak plateau potential was significantly elevated by theophylline alone and further by theophylline + isoproterenol. Theophylline and caffeine (2 mM) may act intracellularly to inhibit the isoproterenol-induced promotion of the early component without impairing the isoproterenol-induced acceleration of relaxation in the canine ventricular muscle.

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