Published Online
on July 29, 2002

A more recent version of this article appeared on August 13, 2002

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Submitted on March 13, 2002
Revised on May 20, 2002
Accepted on May 20, 2002

Preservation of the Baroreceptor Heart Rate Reflex by Chemical Sympathectomy in Experimental Heart Failure

Luca Mircoli MD, Luigi Fedele MD, Marica Benetti MD, Giovanni Battista Bolla MD, Alberto Radaelli MD, Stefano Perlini MD, and Alberto U. Ferrari MD^*

From the Divisione di Cardiologia (L.M.), Ospedale Maggiore Policlinico IRCCS, Milano; Dipartimento di Medicina (A.U.F., L.F., M.B., G.B.B.), Prevenzione e Biotecnologie Sanitarie; Centro Fisiologia Clinica e Ipertensione, Università di Milano and Milano-Bicocca; Divisione di Cardioriabilitazione (A.R.), Ospedale di Seregno, Az. Osp. Vimercate (MI); and IRCCS S. Matteo (S.P.), Pavia, Italy.

^* To whom correspondence should be addressed. E-mail: alberto.ferrari{at}unimib.it.

Background—The mechanisms underlying impaired baroreflex sensitivity in congestive heart failure (CHF) are incompletely understood. The purpose of the present study was to test the hypothesis that this alteration depends on the marked degree of sympathetic overactivity known to characterize the CHF syndrome.

Methods and Results—Eight-week-old rats were subjected to induction of postmyocardial infarction CHF obtained by coronary ligation (Lig), chronic chemical sympathectomy by 6-hydroxydopamine (Sx), both interventions (Sx-Lig), or neither intervention (Veh-Sham, sham surgery, and vehicle administration). Four weeks after infarction, in conscious state, baroreflex sensitivity was assessed from the bradycardic responses to graded phenylephrine-induced elevations in blood pressure (BP). Left ventricular (LV) diameter was assessed by echocardiography, and plasma catecholamines were assayed to estimate sympathetic activity. Lungs were eventually excised and weighed (LW). CHF was associated with the following: (1) no changes in BP and heart rate; (2) sympathetic overactivity (norepinephrine, 320.2±53.8 pg/mL for Veh-Lig versus 173.4±20.5 pg/mL for Veh-Sham, P<0.01), prevented by Sx (181.2±35.5 pg/mL for Sx-Lig versus 159.8±33.1 pg/mL for Sx-Sham, P=NS); (3) LV enlargement (10.3±0.7 mm for Veh-Lig versus 6.8±0.6 mm for Veh-Sham, P<0.01), irrespective of Sx (9.7±0.7 mm for Sx-Lig versus 6.6±0.5 mm for Sx-Sham, P<0.01); (4) pulmonary congestion (LW, 7.55±0.40 mg per gram of body weight for Veh-Lig versus 5.21±0.44 mg per gram of body weight for Veh-Sham, P<0.01), marginally attenuated by Sx (6.54±0.28 mg per gram of body weight for Sx-Lig versus 4.98±0.22 mg per gram of body weight for Sx-Sham, P<0.05); (5) reduction in baroreflex sensitivity (0.443±0.032 ms/mm Hg for Veh-Lig versus 0.860±0.420 ms/mm Hg for Veh-Sham, P<0.01), entirely prevented by Sx (1.217±0.058 ms/mm Hg for Sx-Lig versus 1.345±0.093 ms/mm Hg for Sx-Sham, P=NS).

Conclusions—In early post-MI CHF, sympathectomy only partially attenuated LV dysfunction and entirely prevented baroreflex sensitivity impairment that arises from enhanced sympathetic activity.

Key words: heart failure • baroreceptors • nervous system, sympathetic

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