Vascular and cardiac effects of amlodipine in acute heart failure in dogs.
BACKGROUND
Amlodipine improves exercise capacity in patients with chronic congestive heart failure (HF), but the mechanisms of this effect are unknown.


OBJECTIVE
To test the hypothesis, in a canine model of acute, ischemic HF, that amlodipine increases vascular capacitance and reduces cardiac filling pressures.


METHODS
Amlodipine was given to 13 anesthetized, splenectomized dogs (six controls and seven with HF). Aortic, left ventricular end-diastolic (LVEDP) and portal venous (Pportal) pressures, cardiac output, portal flow (ultrasonic probe) and intestinal blood volume (IBV, 99mTc blood-pool scintigraphy) were measured. Intestinal vascular conductance (= 1/resistance) and vascular capacitance (CAP) were measured before and 15 mins after repetitive 150 micrograms/kg dosages of amlodipine (maximum cumulative dosage, 1000 micrograms/kg). Pportal-IBV curves were obtained by impeding portal flow (pneumatic cuff), and change in CAP was defined by the change in IBV at Pportal = 7.5 mmHg. HF was induced by microsphere embolization of the left coronary artery.


RESULTS
CAP increased in the control group (+ 28%, P < 0.01) but decreased (-9%, P < 0.05) in the HF group. Left ventricular stroke work increased in the control group (P < 0.05), while it decreased (P < 0.05) in the HF group, suggesting a negative inotropic effect. In the control group, LVEDP increased after amlodipine was given (P < 0.05) but did not change significantly in the HF group.


CONCLUSIONS
In the acute experimental HF model, amlodipine failed to increase intestinal vascular CAP or decrease filling pressures, and may have had a negative inotropic effect. The experiment failed to demonstrate a beneficial hemodynamic effect of amlodipine in acute HF, and the mechanism of benefit of this agent in chronic HF remains unclear.
Isaac
D L
DL
Department of Medicine, University of Calgary, Alberta. dlisaac@ucalgary.ca
Belenkie
I
I
Manyari
D E
DE
Tyberg
J V
JV
D000208:Acute Disease; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000704:Analysis of Variance; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D002319:Cardiovascular System / Q000000981:diagnostic imaging / Q000187:drug effects*; D004195:Disease Models, Animal; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D006333:Heart Failure / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D011877:Radionuclide Imaging; D019275:Radiopharmaceuticals; D013670:Sodium Pertechnetate Tc 99m; D013997:Time Factors; D018924:Vascular Capacitance / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D002121:Calcium Channel Blockers; D019275:Radiopharmaceuticals; D017311:Amlodipine; D013670:Sodium Pertechnetate Tc 99m