Ri. Ogilvie et D. Zborowskasluis, EFFECT OF PERINDOPRIL IN PACING-INDUCED CANINE MODELS OF ACUTE AND CHRONIC HEART-FAILURE, Canadian journal of cardiology, 11(10), 1995, pp. 934-940
OBJECTIVE: To examine the effects of perindopril, a nonsulfhydryl-cont
aining angiotensin-converting enzyme inhibitor, on total vascular capa
citance and hemodynamics in acute and chronic dog models of heart fail
ure. METHODS: Acute heart failure was induced by anesthetized, splenec
tomized dogs by a volume load (dextran 70; 20 mL/kg) during rapid righ
t ventricular pacing (RRVP) at 250 beats/min. Pretreatment with perind
opril (0.3 mg/kg daily for six days, n=7) was compared with no treatme
nt (n=7). Total vascular capacitance and compliance were measured from
plots of mean circulatory filling pressure during acetylcholine-induc
ed circulatory arrests at different blood volumes. Chronic heart failu
re 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 complianc
e were measured at baseline and after 33 days of RRVP. RESULTS: Perind
opril treatment did not significantly modify the increased pulmonary c
apillary wedge and mean circulatory filling pressures, reduced total v
ascular compliance or total vascular capacitance associated with the v
olume load and acute RRVP. During chronic RRVP, pu rindopril reduced w
eight gain and the development of ascites, reduced right atrial pressu
re (6.3+/-1.3 versus 10.3+/1.2 mmHg), mean circulatory filling pressur
e (9.3+/-1.0 versus 14.7+/-1.2 mmHg), stressed blood volume (22+/-3 ve
rsus 33+/-4 mL/kg) and central blood volume (10+/-1 versus 14+/-1 mL/k
g) while increasing cardiac output (122+/-9 versus 98+/-7 mL/kg). Howe
ver, the reduction in total vascular capacitance was not attenuated an
d pulmonary capillary wedge pressure was not lowered significantly (18
.5+/-1.5 versus 21.4+/-1.3 mmHg). CONCLUSION: Perindopril failed to mo
dify hemodynamics in the pacing-induced canine model of acute heart fa
ilure but had beneficial effects in the model of chronic heart failure
.