WORKING CAPACITY AND EXPRESSION OF MYOSIN HEAVY-CHAIN ISOFORMS IN SKELETAL-MUSCLE OF CHRONIC-ALCOHOLIC MEN WITHOUT LIVER-DISEASE AFTER 1 DAY AND 4 WEEKS OF ALCOHOL ABSTINENCE

1. The aim of this study was to examine the effect of chronic alcohol ingestion on working capacity and on the expression of myosin heavy ch ain isoforms in fibre types of human skeletal muscle. 2. Six alcoholic men having drunk more than 240 g of alcohol/day for more than 10 year s underwent a test for working capacity and a muscle biopsy on the fir st day of alcohol abstinence (test 1) and again after 4 weeks of absti nence (test 2). The biopsies were analysed using histochemical, immuno chemical and gel-electrophoretic techniques, and the results were comp ared with those from eight age-matched nonalcoholic control subjects. 3. The area of type IIB muscle fibres was decreased by 33% in the alco holic patients compared with normal control subjects at both test 1 an d test 2. The area of type IIA fibres was lower (13%) in alcoholic pat ients at test 1 than in the control group, and increased to the normal level at test 2. 4 . The relative proportion of fibres expressing onl y myosin heavy chain type IIB isoforms was one-third of normal in the alcoholic patients at both tests 1 and 2. The relative proportion of f ibres expressing only myosin heavy chain type IIA isoforms was the sam e in alcoholic patients at test 1 and in normal control subjects, but increased by 25% between test 1 and 2 in the alcoholic group. 5. The r elative proportion of fibres showing coexpression of myosin heavy chai n type IIA/IIB isoforms was about two-thirds of normal in alcoholic pa tients at both test 1 and test 2, whereas fibres with co-expression of myosin heavy chain type I/IIA were not seen in the control group, but were found in the alcoholic group, where they doubled from test 1 to test 2. 6. Thus, chronic heavy alcohol consumption modulates the expre ssion of myosin heavy chain isoforms in human skeletal muscle by decre asing the expression of myosin heavy chain type IIB and increasing the expression of myosin heavy chain type I. After 4 weeks of alcohol abs tinence a shift in the expression of myosin heavy chain type I towards myosin heavy chain type IIA is evident, indicating that the effect of alcohol on myosin heavy chain expression is a reversible process. How ever, to obtain complete recovery with a normal level of myosin heavy chain type IIB expression, more than 4 weeks of abstinence is necessar y.7. Working capacity was low and unchanged by 4 weeks of alcohol abst inence. The low proportion of type IIB (fast twitch glycolytic) fibres at both test 1 and 2 coincided with a low lactate production during m aximal exercise. The increased proportion of type I (slow twitch oxida tive) fibres at test 1 coincided with an preferential lipid oxidation during the working period.