Metabolic and contractile responses of fast- and slow-twitch rat skeletal muscles to ischemia

Abstract

Complete occlusion of blood flow to rat hind limb by tourniquet was used to study the effects of total ischemia for 1, 2, and 3 h on contractile function and metabolic behaviour of two muscles composed predominantly of either fast-twitch (extensor digitorum longus, EDL) or slow-twitch (soleus, SOL) fibres. Percent loss in twitch force (P(t)) was greater (p < 0.05) in SOL than EDL during the first 45 min of ischemia. Following 1 h of ischemia, ATP concentration was lower (p < 0.05) than in the contralateral control (20.8 ± 2.0 vs. 26.4 ± 1.5 mmol/kg dry weight). Thereafter, the decline in ATP was greater, with approximately 95% depleted by 3 h of ischemia (1.46 ± 0.46 mmol/kg dry weight). The effect of ischemia on ATP levels in the SOL was similar to ATP levels in the EDL. In the EDL, 1 h of ischemia also resulted in a large decrement in PCr, from 50.1 ± 2.9 to 11.7 ± 2.4 mmol/kg dry weight, and a large increase in lactate, from 25.0 ± 3.0 to 114 ± 10 mmol/kg dry weight. As ischemia was prolonged, only lactate was increased (p < 0.05) both at 2 h (171 ± 12 mmol/kg dry weight) and 3 h (208 ± 5.4 mmol/kg dry weight). Similar trends were found for SOL. By 3 h of ischemia, glycogen was depleted (p < 0.05) by 88% in EDL and 92% in SOL, respectively. These results support the hypothesis that both high energy phosphate transfer and anerobic glycolysis are of major importance in defending ATP homeostasis, particularly during the 1st h of ischemia, and that the resulting metabolic disturbances are responsible for the large fatigability observed. The mechanisms underlying the greater resistance to fatigue observed for the SOL compared with the EDL during the earlier period of ischemia remain uncertain.