Functional and metabolic consequences of skeletal muscle remodeling in hypothyroidism
McAllister, R.M.; Ogilvie, R.W.; Terjung, R.L.
American Journal of Physiology 260(2 Pt 1): E272-E279
1991
ISSN/ISBN: 0002-9513 PMID: 1996631 Document Number: 368787
Functional and metabolic responses of hypothyroid skeletal muscle were evaluated during steady-state isometric contraction conditions, using an isolated perfused rat hindlimb preparation Treating rats with propylthiouracil (PTU) for 4-5 mo resulted in a 55% decrease (P < 0.001) in citrate synthase activity in plantaris muscle and phenotypic remodeling of the plantaris, evident by a threefold increase in type I fiber area and a 13% decrease in type II fiber area. Perfusion of PTH (n = 9) and control (n = 9) rat hindlimbs of similar size, with similar inflow (.apprx. 10 ml/min) and oxygen content (.apprx. 20 g/100 ml), resulted in similar oxygen deliveries to the contracting muscles (PTU 11.4 .+-. 0.58, control 9.54 .+-. 0.75 .mu.mol .cntdot. min-1 .cntdot. g-1; P > 0.05). Ten-minute tetanic contraction (100 ms at 100 Hz) periods at 4, 8, 15, 30, and 45 tetani/min were elicited in consecutive ascending order. Oxygen consumption (.ovrhdot.VO2) was lower in the PTU group at all contraction frequencies (P < 0.005), with a decrease in peak .ovrhdot.VO2 of 44% (PTU 3.01 .+-. 0.29, control 5.35 .+-. 0.42 .mu.mol .cntdot. min-1 .cntdot. g-1; P < 0.001). Oxygen extraction by the PTU muscle was only .apprx. 25% of that delivered. Developed tension was initially less (15%; P < 0.05) in the PTU group but declined in a similar manner, as a percent of initial, to that of the control group. The slightly lower absolute tension development of the PTU muscle could not account for the large reduction in .ovrhdot.VO2. Thus the oxygen cost of tension development was less in hypothyroid muscle (PTU 16.9 .+-. 2.07, control 24.1 .+-. 2.34 nmol/N; P < 0.05). This was probably related to the increase in slow-twitch fiber content. However, the difference in the measured economy of contraction was sufficiently large to suggest a more complex response involving the remaining fiber mass identified histochemically as fast twitch. Even though profound alterations are induced in skeletal muscle in the absence of normal thyroid function, hypothyroid muscle can perform well when supplied with optimal cardiovascular support.