EFFECTS OF CARDIAC DENERVATION ON DEVELOPMENT OF HEART-FAILURE AND CATECHOLAMINE DESENSITIZATION

Background Two signatures of heart failure are activation of the sympa thetic nervous system and catecholamine desensitization. However, whet her or not the elimination of cardiac nerves affects either the progre ssion of heart failure or catecholamine desensitization is not clear. Methods and Results We studied 8 dogs with selective ventricular dener vation (VD) (surgical technique) and 10 intact dogs, chronically instr umented for measurement of left ventricular (LV) and arterial pressure s, IV dP/dt, LV internal diameter, and wall thickness before and after heart failure was induced by rapid pacing (240 bpm) for 3 to 4 weeks. VD was confirmed by the absence of reflex effects induced by intracar diac veratrine and depletion of tissue norepinephrine and by supersens itive responses to norepinephrine. During the development of heart fai lure, LV end-systolic and end-diastolic stresses and heart rate increa sed, while myocardial contractility, as reflected by LV dP/dt and mean velocity of circumferential fiber shortening corrected for heart rate (Vcf(c)), decreased in both intact and VD dogs. However, the increase s in LV end-diastolic stress and decreases in LV dP/dt as well as the relationship between LV systolic stress and Vcf(c) in heart failure we re less (P<.05) in VD dogs. The responses of LV dP/dt and heart rate t o both isoproterenol and norepinephrine in intact dogs were reduced in heart failure. The physiological desensitization to the inotropic eff ects of isoproterenol and norepinephrine was less in dogs with VD (P<. 05), but chronotropic responses were similar because atrial innervatio n remained intact. Plasma norepinephrine levels were not different in VD dogs (592+/-79 pg/mL) compared with intact dogs (576+/-81 pg/mL) in heart failure. Conclusions Dogs with selective VD tolerated the devel opment of heart failure better than intact dogs and demonstrated signi ficantly less catecholamine desensitization. The latter indicates that intact ventricular innervation is required for physiological expressi on of catecholamine desensitization despite comparable elevation of pl asma catecholamines during the development of heart failure.