d,l-sotalol enhances baroreflex sensitivity in conscious rats surviving acute myocardial infarction

The aim of the present study was to characterize the influence of D,L-sotalol on arterial baroreflex sensitivity (BRS) which is generally considered as an estimate of vagal activity and has prognostic value in patients after myocardial infarction (MI). Conscious rats were studied 3 days after left anterior descending coronary artery ligation (n= 5) or sham-operation (SH, n= 6). BRS was determined by linear regression analysis of the RR-interval (interval between heart beats) and mean arterial pressure changes evoked by i.v. bolus injections of methoxamine (inducing reflex bradycardia, RB) and nitroprusside (inducing reflex tachycardia, RT). In MI-rats heart rate and mean arterial pressure were not significantly different from values in SH-rats, left ventricular end-diastolic pressure was increased and contractility was depressed. The BRS (RB: MI: 0.48 +/- 0.04(*), SH: 0.79 +/- 0.08; RT: MI: 0.41 +/- 0.05(*), SH: 0.86 +/- 0.08 ms mmHg(-1)) ((*)P< 0.05 vs SH) was markedly reduced. d, l -Sotalol (1.5 mg kg(-1)i.v.) reduced heart rate (MI: -11 +/- 3 %(*), SH: -11 +/- 3 %(*)) and mean arterial pressure only moderately [MI: -6 +/- 4 %(n.s.), SH: -7 +/- 2 %(*)], while BRS depression in MI-rats was completely neutralized [RB: MI: 1.08 +/- 0.14(*), SH: 1.19 +/- 0.11(*); RT: MI: 0.84 +/- 0.08(*), SH: 0.88 +/- 0.12 (n.s.) ms mmHg(-1)] ((*)P< 0.05 vs pretreatment). The BRS is reduced in rats early after MI, indicating a depressed reflex vagal activity. Treatment with D,L-sotalol at a dose with little effect on heart rate and mean arterial pressure markedly enhances and, thus, restores BRS in MI-rats. These data suggest that D,L-sotalol has both peripheral and central effects leading to an increase of reflex vagal control of heart rate in rats.