Myocardial adaptation to chronic propranolol therapy in normal rats

The intrinsic myocardial adaptation to chronic beta-blockade was explored in normal male Wistar rats. Propranolol was administered by subcutaneous infusion using osmotic minipumps for 3-4 wk (P group). Heart rate fell by approximately 100 beats/min. A second group of animals was similarly treated but had their pumps removed several days before study (P-R group). Heart rate rose, but remained below base line. Study of isolated ventricular papillary muscle from P, P-R, and age-matched controls (C group) revealed prolonged contraction duration in P and P-R groups, but no change in shortening velocity. A greater shortening of time to peak tension and time to one-half relaxation in response to norepinephrine was demonstrated in P and P-R groups. Acute in vivo or in vitro administration of propranolol had no effect on base-line mechanical performance. No changes in the Ca2+, actin-activated Mg2+ myosin adenosine triphosphatase (ATPase) activity, or myosin isoenzyme distribution were found. Free thyroxine levels were decreased in P but not P-R groups. These findings indicate that chronic propranolol therapy in normal rats slows contraction and relaxation without altering contractility. The greater shortening of contraction duration in response to norepinephrine is partly offset by the prolongation of the base-line contraction.