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 ventricular 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. A total of 14 pigs were studied under control conditions and after the development of pacing-induced CHF (240 beats per minute, 3 weeks, n = 7) or with CHF and acute amlodipine treatment for the last 3 days of pacing (1.5 mg/kg per day, n = 7). Under resting conditions, left ventricular stroke volume (mL) was reduced with CHF compared with the normal state (15+/-2 vs. 31+/-1, p<0.05) and increased with amlodipine treatment (23+/-4, p<0.05). At rest, systemic vascular resistance increased with CHF compared with the normal state (3,078+/-295 vs. 2,131+/-120 dyne x s cm(-5), p<0.05) and was reduced after amlodipine treatment (2,472+/-355 dyne x s cm(-5), p<0.05). With exercise, left ventricular stroke volume remained lower and systemic vascular resistance higher in the CHF group, but was normalized with amlodipine treatment. With exercise, 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 norepinephrine was increased by >5-fold in the CHF group at rest and was not affected by amlodipine treatment. However, with exercise, amlodipine treatment blunted the increase in plasma norepinephrine by >50% when compared with untreated CHF values. Resting plasma endothelin levels increased with CHF compared 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 other vascular beds, acute amlodipine treatment with CHF improved pulmonary and renal blood flow both at rest and with exercise; however, there were no effects 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 neurohormonal effects.
Krombach
R S
RS
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Clair
M J
MJ
Hendrick
J W
JW
Mukherjee
R
R
Houck
W V
WV
Hebbar
L
L
Kribbs
S B
SB
Dodd
M G
MG
Spinale
F G
FG
D017311:Amlodipine / Q000627:therapeutic use*; D000818:Animals; D015986:Confounding Factors, Epidemiologic; D003326:Coronary Circulation / Q000187:drug effects; D004195:Disease Models, Animal; D016232:Endothelins / Q000097:blood*; D004837:Epinephrine / Q000097:blood*; D005080:Exercise Test; D006333:Heart Failure / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood*; D013318:Stroke Volume / Q000187:drug effects; D013552:Swine; D014655:Vascular Resistance / Q000187:drug effects; D014665:Vasodilator Agents / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects
D016232:Endothelins; D014665:Vasodilator Agents; D017311:Amlodipine; D012083:Renin; D004837:Epinephrine