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(Hypertension. 2006;48:93.)
© 2006 American Heart Association, Inc.

Original Articles

Survival Benefits of Different Antiadrenergic Interventions in Pressure Overload Left Ventricular Hypertrophy/Failure

Stefano Perlini; Ivana Ferrero; Giuseppina Palladini; Rossana Tozzi; Chiara Gatti; Monia Vezzoli; Francesca Cesana; Maria Bianchi Janetti; Francesca Clari; Giuseppe Busca; Giuseppe Mancia; Alberto U. Ferrari

From the Clinica Medica II (S.P., I.F., G.P., R.T., F.C.), IRCCS San Matteo, Università di Pavia, Pavia, Italy; Clin Med Gen (G.B.), IRCCS Osp Maggiore, Milano, Italy; Centro Interuniversitario di Fisiologia Clinica e Ipertensione (S.P., M.V., M.B.J., G.M.), Milan, Monza and Pavia, Italy; Dipartimento di Medicina Clinica (I.F., F.C., M.B.J., G.M., A.U.F.), Prevenzione e Biotecnologie Sanitarie, Università Milano-Bicocca, Milan, Italy; and Divisione di Riabilitazione Cardiologica (A.U.F.), Ospedale San Gerardo, Monza, Italy.

Correspondence to Alberto U. Ferrari, Centro Fisiologia Clinica e Ipertensione, Via F. Sforza, 35, 20122 Milan, Italy. E-mail a.ferrari{at}hsgerardo.org

We observed previously that in rats with aortic banding (Bd), development of left ventricular (LV) hypertrophy is opposed by ß-blockade, whereas interventions interfering with -adrenoceptor function also inhibit interstitial fibrosis. To assess whether these differential structural effects do translate into different effects on LV function and on heart failure mortality, Bd or sham Bd 8-week–old rats were randomized to vehicle treatment (Vh), chemical sympathectomy ([Sx] 6-hydroxydopamine, 150 mg/kg IP twice a week), ß-adrenoceptor blockade (propranolol [Pro], 40 mg/kg per day PO), or -adrenoceptor blockade (doxazosin [Dox], 5 mg/kg per day PO). After monitoring survival for 10 weeks, the survivors were anesthetized to undergo echocardiography and intraarterial blood pressure measurement. Bd-Vh rats showed increased LV and lung weights, as well as LV dilation, depressed endocardial and midwall fractional shortening and a restrictive transmitral diastolic flow velocity pattern. Compared with Bd-Vh rats, all of the actively treated Bd rats showed less LV hypertrophy, LV dilation, and lung congestion but no less depression of midwall fractional shortening. In contrast, Sx and Dox but not Pro treatment were also associated with lesser degrees of diastolic dysfunction and, even more importantly, with a striking increase in survival (sham banded rats, 100%; Bd-Vh, 40%; Bd-Pro, 51%; Bd-Sx, 83%; and Bd-Dox, 82%). Although Pro, Sx, and Dox provide similar midterm protection from development of LV hypertrophy and dysfunction and from circulatory congestion, only Sx and Dox favorably affected mortality. These findings indicate that in the aortic banding rat model, -adrenoceptors are importantly involved in the pathogenesis of cardiovascular deterioration and disease progression.

Key Words: heart failure • hypertrophy • sympathectomy • rats • receptors, adrenergic alpha • ventricular function, left