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

Hidekazu Suzuki, David C. Poole, Benjamin W. Zweifach, Geert W. Schmid-Schönbein

Research output: Contribution to journalArticle

34 Citations (Scopus)

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 (ΔΨ) 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.

Original languageEnglish
Pages (from-to)2892-2897
Number of pages6
JournalJournal of Clinical Investigation
Volume96
Issue number6
DOIs
Publication statusPublished - 1995 Dec

Keywords

  • dimethylthiourea
  • ischemia-reperfusion
  • mitochondria
  • oxygen radicals
  • spinotrapezius muscle

ASJC Scopus subject areas

  • Medicine(all)

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