Myocardial effects of early therapy with perindopril during experimental cardiomyopathy.
The effects of chronic angiotensin-converting enzyme (ACE) inhibition on intrinsic myocardial contractility of the failing myocardium have been poorly documented. In the present study, inotropy, lusitropy, and economy of force generation were studied in vitro in papillary muscles from cardiomyopathic Syrian hamster (CSH) under early perindopril therapy, i.e., therapy begun at a stage when experimental heart failure was not yet observed. One-month-old CSH from the dilated strain Bio 53.58 were randomly treated over a 5-month period with either the ACE inhibitor perindopril 1 mg/kg/day (n = 11) or placebo (n = 11), and 7 age-matched controls were given placebo. Compared with control, placebo had a lower maximum shortening velocity (Vmax) (p < 0.01) and normalized total force (p < 0.05), and a lower curvature of the force-velocity relationship (p < 0.01). It has been shown that the higher the value of the curvature, the better the myothermal economy of force generation. Compared with placebo, perindopril had a 68% inhibition of plasma ACE activity and a greater Vmax (p < 0.05), whereas total force/mm2 was similar. This resulted in a lesser decrease of the curvature compared to control (p < 0.05). Placebo had a decreased peak lengthening velocity and rate of force decline. However, compared to control, no intrinsic abnormalities of the relaxation phase were observed in either placebo or perindopril when relaxation parameters were corrected for the lower systolic performance.(ABSTRACT TRUNCATED AT 250 WORDS)
Chemla
D
D
INSERM U275, Loa-Ensta, Ecole Polytechnique, Palaiseau, France.
Scalbert
E
E
Desché
P
P
Pourny
J C
JC
Lambert
F
F
Lecarpentier
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D006224:Cricetinae; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use*; D008647:Mesocricetus; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects; D020913:Perindopril; D011897:Random Allocation; D013268:Stimulation, Chemical
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril