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Because the mechanism of adverse reactions to abrupt withdrawal of propranolol in patients with coronary disease is an enigma, we studied the effect of cessation of propranolol on beta receptor reactivity to catecholamine stimulation. Heart rate and maximum rate of rise of left ventricular pressur (dP/dt max) during isoproterenol infusions and plasma free fatty acids (FFAs) after epinephrine infusions were measured in six conscious dogs before, during and after four weeks of oral propranolol (40 mg p.o. q8h). Rises in heart rate, dP/dt max and FFAs were blocked during propanolol administration. Twenty-four hours after withdrawal from propranolol, heart rate and dP/dt max responses remained significantly attenuated, although FFA responses were at premedication levels. The 72-hour, 96-hour and one week postmedication responses did not differ from premedication values. Thus, partial beta blockade of the heart was still present at 24 hours and no evidence of heightened beta receptor sensitivity was detected on repeated study one week after withdrawal from a long-term, high dose propranolol regimen.

Hemodynamic and metabolic response after abrupt uithdrawal of long-term propranolol.