PROPRANOLOL THERAPY IN EXPERIMENTAL HEART-FAILURE IN RABBITS IMPROVESCARDIAC RESPONSE TO CATECHOLAMINES WITHOUT BETA-ADRENOCEPTOR UP-REGULATION

Beta-blockade has been shown to improve cardiac response to catecholam ines in heart failure but cellular mechanisms of the improvement are u nknown. The effect on left ventricular function of a 14 day propranolo l treatment was studied in seven treated and eight non-treated rabbits with experimental heart failure. All animals were subjected to a volu me (aortic insufficiency) plus pressure (aortic constriction) overload and were instrumented with a left ventricular catheter and ultrasonic crystals measuring anteroposterior left ventricular diameter. Beta-ad renoceptors were measured using I-125-Cyanopindolol in crude membranes . With isoproterenol, the heart rate was slower in treated rabbits tha n in non-treated rabbits (p < 0.005) and isoproterenol increased more systolic diameter shortening in treated than in non-treated rabbits (p < 0.05). With norepinephrine, for matched pressures, % Delta D increa sed in the treated group but it did not change in the non-treated grou p. This improvement of ventricular function was due, in a large part, to an increased diastolic response to norepinephrine: end-diastolic di ameter increased in the treated group but not in the non-treated group . In contrast with the improved ventricular response to catecholamines , beta-adrenergic receptor density in the treated group was identical to that of the non-treated group (27.8 fmoles/mg/proteins) and was sig nificantly lower than that of normal rabbits (58.2 fmoles/mg, p < 0.01 ). The improvement of ventricular response to catecholamines appears t o be due to a myocardial protection by propranolol against the toxic e ffect of catecholamines in heart failure and not, at least in this mod el, to an up-regulation of beta-adrenoceptors.