Adaptation to prolonged beta-blockade of rabbit atrial, purkinje, and ventricular potentials, and of papillary muscle contraction. Time-course of development of and recovery from adaptation.

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Abstract
Groups of littermate rabbits were treated for various periods up to 6 weeks with twice daily subcutaneous injections of saline, D-propranolol, DL-propranolol, or metoprolol, the latter two at doses equivalent to those used in clinical therapy. Investigations were made at a sufficient time (20-24 hours after the most recent dose) to ensure that the drugs would have been eliminated from the body, so that any observed changes would represent an adaptation to treatment, not effects due to the presence of the drugs. The ECG was recorded in vivo at regular intervals during treatment. After several days, Q-Tc was prolonged by the beta-blockers, reaching a peak effect at about 3 weeks from the start of treatment, and returned to control values at 3 weeks after cessation of treatment. Action potential duration, measured in vitro by intracellular recording, was also prolonged uniformly in atria and ventricles over a similar time-course, unrelated to cardiac frequency, but shortened in distal Purkinje cells. Peak tension was not altered in propranolol-adapted papillary muscles, but the relationship of rate of rise of tension was steeper. It is concluded that these effects represent a myocardial adaptation to prolonged beta-blockade.