CENTRAL GAIN OF THE CARDIAC SYMPATHETIC AFFERENT REFLEX IN DOGS WITH HEART-FAILURE

Previous studies from our laboratory have shown that the cardiac sympa thetic afferent reflex is enhanced in dogs with experimental heart fai lure. The aim of the present study was to determine if the central gai n of the cardiac sympathetic afferent reflex was also enhanced in dogs with heart failure. Fifteen dogs with pacing-induced heart failure we re used in this study. Seventeen sham-operated dogs served as control. At the time of the acute experiment the dogs were anesthetized with a lpha-chloralose. Arterial blood pressure, heart rate, and renal sympat hetic nerve activity were recorded. After sinoaortic denervation and c ervical vagotomy, a thoracotomy was performed in the second intercosta l space. The left stellate ganglion was identified, and the left cardi ac sympathetic nerves were cut. The central end of the left cardiac sy mpathetic nerves was placed on bipolar stimulating electrodes. The ren al sympathetic nerve activity responses to electrical stimulation (30 Hz, 1 ms with varying voltages from 1 to 10 V; or 10 V, 1 ms with vary ing frequencies from 1 to 30 Hz) of the afferent cardiac sympathetic n erves were compared between sham and heart failure groups. Reflex rena l sympathetic nerve activity responses to stimulation of the cardiac s ympathetic nerves were significantly greater in the heart failure grou p compared with that in the sham group (21.4 +/- 3.2 vs. 9.8 +/- 2.9% at 10 V, 30 Hz and 27.7 +/- 4.5 vs. 9.9 +/- 3.4% at 30 Hz, 10 V, heart ; failure vs. sham group, respectively; for both relationships, P < 0. 05). This enhanced central gain of the cardiac sympathetic afferent re flex in the heart failure group was significantly attenuated after int ravenous and cerebroventricular injection of the angiotensin II recept or antagonist losartan (5 mg/kg iv and 0.125 mg/kg in 0.1 ml icv). The se data suggest that the central gain of the cardiac sympathetic affer ent reflex is enhanced in dogs with heart failure and central angioten sin II plays an important role in this enhanced response.