Load-insensitive relaxation caused by hypoxia in mammalian cardiac muscle.

The relaxation of isolated cardiac muscles from mammals was recently shown to be sensitive to the loading conditions because the time course of relaxation could be changed by changing the load. This effect apparently is related to the amount and functional status of the sarcoplasmic reticulum. The purpose of this study was to determine whether hypoxia affected the load sensitivity of papillary muscles isolated from both rats and cats. We used three mechanical tests to establish the presence of load-sensitive relaxation. First, we superimposed records of isotonic contractions at increasing afterloads up to isometric contraction. From these records we measured the ratio (tRi) which was the time from the initiation of the contraction to the initial decay of force at each isotonic afterload, divided by the time it took for the force of an isometric contraction to relax to that same afterload. If the tRi was less than 1.0, then the muscle was load sensitive. Hypoxia caused the loss of load-sensitive relaxation in isotonically contracting rat papillary muscles since the tRi ratios were not significantly different from 1.0 at all afterloads. Both hypoxia and caffeine were required to make cat papillary muscles load insensitive. Second, during hypoxia, loads added in midcontraction did not induce early relaxation in rat papillary muscles, but still did so in cat muscles. Hypoxia plus caffeine eliminated this load-induced early relaxation in cat papillary muscles. Third, physiologically contracting muscles made hypoxic did not lengthen earlier in response to an additional load. This decrease of load sensitivity under hypoxic conditions could contribute to the relaxation abnormalities observed during regional wall motion studies. Circ Res 48: 797-803, 1981