Contractile function of papillary muscle from rats with different infarct size after beta-adrenergic blockade and ACE-inhibition.
We tested whether ACE-inhibition with ramipril (A), beta-adrenergic blockade with metoprolol (beta) or combined treatment (beta A) for 6 weeks after inducing myocardial infarction in rats by left coronary artery ligation modifies contractile function of hypertrophied papillary muscle from left ventricles with different infarct size (IS) compared to a placebo group (P). At IS<40% of left ventricle, contraction and relaxation were less impaired than at IS>40% compared to sham operated rats (SO). Isometrically developed peak force and calcium sensitivity of myofilaments, measured in skinned fibres, were significantly higher in beta. Treatment with ramipril or metoprolol improved contraction rate and force development, respectively, mainly at IS<40%, but deteriorated relaxation rate. ACE-inhibition and beta-adrenergic blockade had no significant improving effect on the relaxation rate and further characteristics of the contractile function at IS>40%, although combined treatment reduced the infarct size and ramipril treatment suppressed the development of hypertrophy. Post-extrastimulatory potentiation was increased in beta and beta A at IS>40%. Post-rest potentiations were influenced hardly at IS<40% and were significantly smaller in A at IS>40%. The twitch-to-twitch decay of the potentiations was faster at IS>40%. Increase in the degree of post-extrastimulatory potentiation, steeper twitch-dependent decay of the potentiations and loss of rest-dependent potentiation at IS>40% indicate relatively increased trans-sarcolemmal Ca2+ transports via Ca2+ channels and Na+/Ca2+ exchange, partly modified by ramipril and metoprolol. The results demonstrate that ACE-inhibition and beta-adrenergic blockade induce a dissociation between trophic effects and phenotypic effects on contractile function after chronic infarction.
Wagner
K D
KD
Clinic Internal Medicine I, Humboldt-University, Berlin, 10098, Germany.
Theres
H
H
Born
A
A
Strube
S
S
Wunderlich
N
N
Pfitzer
G
G
Baumann
G
G
Günther
J
J
D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D004359:Drug Therapy, Combination; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D018485:Muscle Fibers, Skeletal / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects*; D009203:Myocardial Infarction / Q000188:drug therapy*; D010210:Papillary Muscles / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002118:Calcium