Effect of perindopril in pacing-induced canine models of acute and chronic heart failure.
OBJECTIVE
To examine the effects of perindopril, a nonsulfhydryl-containing angiotensin-converting enzyme inhibitor, on total vascular capacitance and hemodynamics in acute and chronic dog models of heart failure.


METHODS
Acute heart failure was induced in anesthetized, splenectomized dogs by a volume load (dextran 70, 20 mL/kg) during rapid right ventricular pacing (RRVP) at 250 beats/min. Pretreatment with perindopril (0.3 mg/kg daily for six days, n = 7) was compared with no treatment (n = 7). Total vascular capacitance and compliance were measured from plots of mean circulatory filling pressure during acetylcholine-induced circulatory arrests at different blood volumes. Chronic heart failure was induced by continuous RRVP in splenectomized dogs treated with perindopril (0.3 mg/kg daily, n = 8), which were compared with untreated dogs (n = 8). Hemodynamics and total vascular capacitance and compliance were measured at baseline and after 33 days of RRVP.


RESULTS
Perindopril treatment did not significantly modify the increased pulmonary capillary wedge and mean circulatory filling pressures, reduced total vascular compliance or total vascular capacitance associated with the volume load and acute RRVP. During chronic RRVP, perindopril reduced weight gain and the development of ascites, reduced right atrial pressure (6.3 +/- 1.3 versus 10.3 +/- 1.2 mmHg), mean circulatory filling pressure (9.3 +/- 1.0 versus 14.7 +/- 1.2 mmHg), stressed blood volume (22 +/- 3 versus 33 +/- 4 mL/kg) and central blood volume (10 +/- 1 versus 14 +/- 1 mL/kg) while increasing cardiac output (122 +/- 9 versus 98 +/- 7 mL/kg). However, the reduction in total vascular capacitance was not attenuated and pulmonary capillary wedge pressure was not lowered significantly (18.5 +/- 1.5 versus 21.4 +/- 1.3 mmHg).


CONCLUSIONS
Perindopril failed to modify hemodynamics in the pacing-induced canine model of acute heart failure but had beneficial effects in the model of chronic heart failure.
D000208:Acute Disease; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D004285:Dogs; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D020913:Perindopril; D018924:Vascular Capacitance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril