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We tested whether ACE-inhibition with ramipril (A),β-adrenergic blockade with metoprolol (β) or combined treatment (βA) for 6 weeks after inducing myocardial infarction in rats by left coronary artery ligation modifies contractile funtion of hypertrophied papillary muscle from left venticles 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 inβ. Treatment with ramipril or metoprolol improved contraction rate and force development, respectively, mainly at IS<40%, but deteriorated relaxation rate. ACE-inhibition andβ-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 inβandβA 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 andβ-adrenergic blockade induce a dissociation between trophic effects and phenotypic effects on contractile function after chronic infarction.

We treated 6 patients with Stage II primary biliary cirrhosis with cholic acid (CA) 10 mg · kg-1 per day for 3 months and then with the same dose of ursodeoxycholic acid (UDCA). A matching group of 6 patients was observed for 3 months without any therapy. Liver function tests and serum and stool bile acids were investigated before, during and at the end of CA and UDCA therapy.