ANALYSIS OF BAROREFLEX CONTROL OF HEART-RATE IN CONSCIOUS DOGS WITH PACING-INDUCED HEART-FAILURE

The autonomic components of the baroreflex control of heart rate were evaluated in conscious mongrel dogs before and after 4-6 weeks of ventricular pacing (250 beats/min). Arterial baroreflex sensitivity (BRS) was determined by the slopes of linear regression of pulse interval versus the preceding systolic arterial pressure in response to bolus injections of either phenylephrine or nitroglycerin. Brs was significantly depressed in the heart failure state ]nitroglycerin slope, 5.0 +/- 2.7 (mean +/- Sd) versus 16.6 +/- 5.1 msec/mm Hg, p < 0.005; phenylephrine slope, 15.0 +/- 14.8 versus 32.0 +/- 26.7 [msec/mm Hg, p < 0.005]. There was no depression in BRS in dogs that were used as time controls or were acutely paced for 30 minutes. After beta-1-adrenergic blockade with metoprolol, the resting heart rate in the heart failure state was depressed more than in the normal state (-17.0 +/- 5.0% versus -3.2 +/- 3.4%, p < 0.001). Atropine significantly increased resting heart rate more in the normal state than in the heart failure state (115.8 +/- 36.7% versus 25.4 +/- 14.5%, p < 0.005). Thus, dogs in the heart failure state appear to have high resting cardiac sympathetic tone and low resting vagal tone. For nitroglycerin administration, metoprolol depressed BRS by 47.6 +/- 26.3% in the normal state and by 63.6 +/- 58.5% in the heart failure state. Atropine decreased the BRS by 86.7 +/- 7.8% in the normal state and by 39.5 +/- 30.2 in the heart failure state. Although these were significantly different (p < 0.05), an analysis of covariance indicates that these differences in response in the normal and heart failure states are largely due to the low resting BRS in the heart failure state. For phenylephrine responses, metoprolol had no significant influence on BRS in either the normal or the heart failure state. In contrast, BRS in both normal and heart failure states was nearly abolished by atropine. There was no difference in the extent of BRS inhibition after atropine between the normal and the heart failure state in response to phenylephrine. These data provide the first description of the autonomic control of heart rate in pacing-induced heart failure. In contrast to other models of heart failure, the primary abnormality is seen during baroreceptor unloading with nitroglycerin. The abnormality is largely manifest by a decrease in sympathetic activation in heart failure when the baroreceptors are unloaded.