Amlodipine therapy in congestive heart failure: Hemodynamic and neurohormonal effects at rest and after treadmill exercise

This study examined the acute effects of amlodipine treatment on left ventr icular pump function, systemic hemodynamics, neurahormonal status, and regi onal blood flow distribution in an animal model of congestive heart failure (CHF), both at rest and with treadmill exercise. A total of 14 pigs were s tudied under control conditions and after the development of pacing-induced CHF (240 beats per minute, 3 weeks, n = 7) or with CHF and acute amlodipin e treatment for the last 3 days of pacing (1.5 mg/kg per day, n 7). Under r esting conditions, left ventricular stroke volume (mt) was reduced with CHF compared with the normal state (15 +/- 2 vs 31 +/- 1, p <0.05) and increas ed with amlodipine treatment (23 +/- 4, p <0.05). At rest, systemic vascula r resistance increased with CHF compared with the normal state (3,078 +/- 2 95 vs 2,131 +/- 120 dyne.s cm(-5) p <0.05) and was reduced after amlodipine treatment (2,472 +/- 355 dyne.s cm(-5), p <0.05). With exercise, left vent ricular stroke volume remained lower and systemic vascular resistance highe r in the CHF group, but was normalized with amlodipine treatment. With exer cise, left ventricular myocardial blood flow increased from resting values, but was reduced from the normal state with CHF (normal: 1.69 +/- 0.12 to 7 .62 +/- 0.74 mL/min per gram vs CHF: 1.26 +/- 0.12 to 4.77 +/- 0.45 mL/min per gram, both p <0.05) and was normalized with acute amlodipine treatment (1.99 +/- 0.35 to 6.29 +/- 1.23 mL/min per gram). Resting plasma norepineph rine was increased by >5-fold in the CHF group at rest and was not affected by amlodipine treatment. However, with exercise, amlodipine treatment blun ted the increase in plasma norepinephrine by >50% when compared with untrea ted CHF values.-Resting plasma endothelin levels increased with CHF compare d with the normal state (10.9 +/- 0.9 vs 2.8 +/- 0.4 fmol/ml, p <0.05) and was reduced with amlodipine treatment (7.5 +/- 1.5 fmol/mL, p <0.5). In oth er vascular beds, acute amlodipine treatment with CHF improved pulmonary an d renal blood flow both at rest and with exercise; however, there were no e ffects observed on skeletal muscle blood flow. With the development of CHF, acute amlodipine treatment does not negatively influence left ventricular pump function, but rather may provide favorable hemodynamic and neurohormon al effects. (C) 1999 by Excerpta Medica, Inc.