Plasticity of cardiovascular chemoreflexes after prolonged unilateral carotid body denervation: implications for its therapeutic use

Unilateral carotid body denervation has been proposed as treatment for sympathetic hyperactivity-related human disorders. Its therapeutic effectiveness for maintaining a persistent decrease in the sympathetic outflow activity will depend on the absence of compensatory chemoreflex plasticity in the remnant carotid and aortic afferents. Here, we suggest that the integrity of central afferents after carotid body denervation is essential to prevent the emergence of plastic functional changes on the contralateral “intact” carotid nerve.

Abstract 17082: Carotid Body Denervation Improves Autonomic Balance and Prevents the Worsening of Heart Failure in Rats After Large Myocardial Infarction

Introduction: Carotid body denervation (CBD) abolishes the carotid body hypersensitivity induced sympathoexcitatory hypertension. Since the carotid body hypersensitivity is a salient feature and predicts poor outcome of chronic heart failure (CHF), we hypothesized that CBD restores normal autonomic balance, thus improves CHF in rats after large myocardial infarction (MI). Methods: We created MI in 8 weeks Sprague-Dawley rats. Surviving rats at 2 weeks after MI were randomized into CBD (n=11) and sham-operated (Sham; n=13) groups. We removed the tissues around the carotid bifurcation and established CBD. In some rats (Sham; n=5, CBD; n=5), we telemetrically recorded heart rate (HR). One month after CBD, we compared physiological, histological and immunochemical findings between CBD and Sham. Results: CBD significantly reduced HR (337±15 vs. 364±12 bpm, p<0.05). CBD markedly increased the power spectral density of HR in the high frequency range (81.0±9.5 vs. 29.0±8.2 n.u., p<0.05) and decreased that of the low frequency/high frequency ratio (0.6±0.2 vs. 1.8±0.5, p<0.05) indicating the restoration of autonomic balance. CBD significantly reduced biventricular weight (3.1±0.3 vs. 3.7±0.3 g/kg, p<0.05) and left ventricle (LV) end-diastolic pressure (22±5 vs. 33±5 mmHg, p<0.01) and increased maximum LV dp/dt (5118±809 vs. 4217±472 mmHg/sec, p<0.05). CBD reduced lung weight (a marker of pulmonary edema) (6.8±2.0 vs. 12.4±1.5 g/kg, p<001). Furthermore, CBD reduced plasma brain natriuretic peptide (70±43 vs. 166±71 pg/ml, p<0.01) and plasma norepinephrine as an index of sympathetic drive (384±202 vs. 1048±997 pg/ml, p<0.05). CBD significantly reduced the number of inflammatory macrophages (345±45 vs. 474±73 counts/mm2, p<0.05) in the LV and the plasma concentration of interleukin-1β (14.3±4.7 vs. 24.5±11.8 pg/ml, p<0.05) indicating that CBD also suppressed the inflammatory response in CHF. Conclusions: CBD restores normal autonomic balance and prevents the worsening of heart failure in rats after large myocardial infarction. CBD may serve as a novel neuro-modulatory therapy for CHF patients.