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(Circulation. 1998;98:1666-1674.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Chronic Amlodipine Treatment During the Development of Heart Failure

Francis G. Spinale, MD, PhD; Rupak Mukherjee, PhD; R. Stephen Krombach, BA; Mark J. Clair, BS; Jennifer W. Hendrick, BS; Ward V. Houck, MD; Latha Hebbar, MD; Scott B. Kribbs, BS; James L. Zellner, MD; ; Michael G. Dodd, PhD

From the Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston, and Pfizer Central Research, Sandwich, UK (M.G.D.).

Correspondence to Francis G. Spinale, MD, PhD, Cardiothoracic Surgery, Room 418 CSB, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425.

Background—This study examined the effects of chronic amlodipine treatment on left ventricular (LV) pump function, systemic hemodynamics, neurohormonal status, and regional blood flow distribution in an animal model of congestive heart failure (CHF) both at rest and with treadmill exercise. In an additional series of in vitro studies, LV myocyte contractile function was examined.

Methods and Results—Sixteen pigs were studied under normal control conditions and after the development of chronic pacing–induced CHF (240 bpm, 3 weeks, n=8) or chronic pacing and amlodipine (1.5 mg · kg^-1 · d^-1, n=8). Under ambient resting conditions, LV stroke volume (mL) was reduced with CHF compared with the normal control state (16±2 versus 31±2, P<0.05) and increased with concomitant amlodipine treatment (29±2, P<0.05). At rest, systemic and pulmonary vascular resistance (dyne · s^-1 · cm^-5) increased with CHF compared with the normal control state (3102±251 versus 2156±66 and 1066±140 versus 253±24, respectively, both P<0.05) and were reduced with amlodipine treatment (2108±199 and 480±74, respectively, P<0.05). With CHF, LV stroke volume remained reduced and was associated with a 40% reduction in myocardial blood flow during treadmill exercise, whereas chronic amlodipine treatment normalized LV stroke volume and improved myocardial blood flow. Resting and exercise-induced plasma norepinephrine levels were increased by >5-fold in the CHF group and were reduced by 50% from CHF values with chronic amlodipine treatment. Resting plasma endothelin (fmol/mL) increased with CHF compared with the normal state (10.4±0.9 versus 3.1±0.3, P<0.05) and was reduced with amlodipine treatment (6.6±1.1, P<0.5). With CHF, LV myocyte velocity of shortening (µm/s) was reduced compared with normal controls (39±1 versus 64±1, P<0.05) and was increased with chronic amlodipine treatment (52±1, P<0.05).

Conclusions—Chronic amlodipine treatment in this model of developing CHF produced favorable hemodynamic, neurohormonal, and contractile effects in the setting of developing CHF.

Key Words: calcium channel blockers • heart failure • blood flow • hormones

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