CHRONIC AMLODIPINE TREATMENT DURING THE DEVELOPMENT OF HEART-FAILURE

Background-This study examined the effects of chronic amlodipine treat ment on left ventricular (LV) pump function, systemic hemodynamics, ne urohormonal status, and regional blood flow distribution in an animal model of congestive heart failure (CHF) both at rest and with treadmil l exercise. In an additional series of in vitro studies, LV myocyte co ntractile 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 a nd amlodipine (1.5 mg.kg(-1).d(-1), n=8). Under ambient resting condit ions, LV stroke volume (mL) was reduced with CHF compared with the nor mal control state (16+/-2 versus 31+/-2, P<0.05) and increased with co ncomitant 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 an d 1066+/-140 versus 253+/-24, respectively, both P<0.05) and were redu ced with amlodipine treatment (2108+/-199 and 480+/-74, respectively, P<0.05). With CHF, LV stroke volume remained reduced and was associate d with a 40% reduction in myocardial blood flow during treadmill exerc ise, whereas chronic amlodipine treatment normalized LV stroke volume and improved myocardial blood flow. Resting and exercise-induced plasm a 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 reduce d with amlodipine treatment (6.6+/-1.1, P<0.5). With CHF, LV myocyte v elocity of shortening (mu m/s) was reduced compared with normal contro ls (39+/-1 versus 64+/-1, P<0.05) and was increased with chronic amlod ipine treatment (52+/-1, P<0.05). Conclusions-Chronic amlodipine treat ment in this model of developing CHF produced favorable hemodynamic, n eurohormonal, and contractile effects in the setting of developing CHF .