Temporal correlation between maximum tetanic force and cell death in postischemic rat skeletal muscle.

Abstract

To gain insight into the mechanisms responsible for muscle dysfunction after ischemia-reperfusion, a rat spinotrapezius muscle preparation was developed which enabled sequential measurements of in vivo maximum tetanic force production and cell death assessed using digital microfluorographic determination of propidium iodide (PI) staining. After 60 min of no-flow ischemia, maximum tetanic force fell significantly during 90 min of reperfusion compared with control, nonischemic muscles. The most striking fall was evident within 30 min of reperfusion and occurred concomitant with an explosive increase in PI-positive myocyte nuclei. Treatment with the oxygen radical scavenger, dimethylthiourea, attenuated both the fall in force and increased PI staining. Indeed, the rise in PI-positive nuclei correlated closely (r = 0.728) with the reduction of maximum tetanic force developed following ischemia and reperfusion under all conditions. Superoxide dismutase also attenuated the rise in PI-positive nuclei. Assessment of mitochondrial inner membrane potential (A+) using Rhodamine 123 fluorescence revealed that myocytes with the lowest initial mitochondrial membrane potential were subject to the greatest injury after 90 min of reperfusion (r = 0.828). These results support the hypothesis that myocyte injury, as visualized by PI-staining, reflects an impaired contractile function in fibers with a low oxidative potential which is likely mediated by oxygen radicals. (J. Clin. Invest. 1995.

Intracellular calcium accumulation following eccentric contractions in rat skeletal muscle in vivo: role of stretch-activated channels

“…The time course of [Ca 2ϩ ]i change was observed after each of 10 discrete sets of ISO muscle stimulation, in a similar fashion to that described previously (46). Specifically, each set consisted of the muscle being stimulated tetanically at resting spinotrapezius sarcomere length (100 Hz, 5-8 V, stimulus duration 700 ms, 2.6-to 2.8-m sarcomere length) every 3 s for 2.5 min (i.e., 50 contractions).…”

“…For example, Ivanics and colleagues (23) have described a selective damage (and [Ca 2ϩ ] i accumulation) in oxidative type I fibers following an ischemia-reperfusion protocol in the spinotrapezius muscle. In contrast, Suzuki and colleagues (46) found that an ischemiareperfusion protocol selectively damaged those fibers with a low oxidative capacity (most likely type IIb fibers, as visualized using rhodamine-123 to identify relative mitochondrial content). When muscle is injured consequent to ECC contractions, muscle fibers may be selectively damaged, and, as these fibers subsequently produce less force, the remaining healthy fibers may be subjected to greater stresses and are likely to suffer progressively more injury (14).…”

Downhill running: a model of exercise hyperemia in the rat spinotrapezius muscle

“…Unfortunately, there are very few muscles anatomically and optically suitable for transmission light microscopy. Of these, the rat spinotrapezius muscle possesses the following singular advantages: 1) it can be exteriorized and transilluminated without disruption of the nervous or primary vascular supplies (2,12,28,40); 2) it comprises a mosaic of the three principal fiber types found in mammalian muscle (8); and 3) the oxidative capacity approximates that found in the untrained human quadriceps (8,22). Consequently, it is not surprising that intravital microscopy of the spinotrapezius has been integral to our understanding of muscle microcirculation in health (4,21,23,25,31,37,39) and chronic diseases such as heart failure (15), Type 1 diabetes (18), and hypertension (13).…”

Dissociation between skeletal muscle microvascular Po2and hypoxia-induced microvascular inflammation

“…Furthermore, leukocyte adherence to the venular endothelium occurs predominantly during reperfusion rather than during ischemia (4,7,8,22,23), whereas in hypoxia this phenomenon occurs when PO 2 is reduced (19,20,24); during normoxic recovery, leukocyte-endothelial adhesive interactions actually subside (19,20,24). Systemic hypoxia in anesthetized rats, however, results in marked arterial hypotension (26).…”