Effects of perindopril on myocardial inotropy, lusitropy and economy, and on diaphragmatic contractility in the cardiomyopathic Syrian hamster.
Over a 5-month period, 22 1-month-old cardiomyopathic Syrian hamsters were randomly treated with either angiotensin-converting enzyme inhibitor (perindopril 1 mg/kg/day) (PE, n = 11) or placebo (PL, n = 11), and 7 age-matched controls (C) were given placebo. Compared to C, mechanics of left ventricular papillary muscles from PL exhibited a lower maximum unloaded shortening velocity (Vmax) (P less than .01) and normalized peak active force (P less than .05), and a significantly less curved shape of the force-velocity (F-V) relationship (P less than .01). The curvature of the F-V relationship has been proposed as a reflection of the efficiency of muscle contraction. Compared to PL, PE had a 68% inhibition of plasma ACE activity and a greater Vmax (P less than .05), whereas active force (AF) was similar. This resulted in a lesser decrease of the curvature of the F-V relationship compared to that of C (P less than .05). Muscle strips from the ventral costal diaphragm were dissected from the muscle in situ. In both twitch and tetanus modes, intrinsic mechanical performance of diaphragm muscle was markedly decreased in PL compared to C as regards normalized positive (+dF/dtmax/mm2) and negative (-dF/dtmax/mm2) peak rate of force, and normalized peak active force (AF/mm2) (P less than .01 each). In both twitch and tetanus modes, PE had an increased +dF/dtmax/mm2 (P less than .05), -dF/dtmax/mm2 and AF/mm2 (P less than .01 each), compared to PL. These results indicate 1) that the low inotropic state observed in cardiomyopathic Syrian hamsters was associated with decreased myothermal economy of cardiac contraction and with a major impairment of diaphragm intrinsic contractility, and 2) that early therapy with angiotensin-converting enzyme inhibitor helped to preserve myocardial contractility and economy, and diaphragm contractility.
Chemla
D
D
INSERM U275-Loa-Ensta-Ecole Polytechnique, Palaiseau, France.
Scalbert
E
E
Desche
P
P
Pourny
J C
JC
Lambert
F
F
Lecarpentier
Y
Y
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D009202:Cardiomyopathies / Q000503:physiopathology*; D006224:Cricetinae; D003964:Diaphragm / Q000503:physiopathology*; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects*; D010210:Papillary Muscles / Q000187:drug effects / Q000502:physiology; D020913:Perindopril; D013268:Stimulation, Chemical
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; D020913:Perindopril