title: 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 (deltapsi) 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.
authors.affiliation: Department of Bioengineering, Institute for Biomedical Engineering, University of California San Diego, La Jolla, 92093-0412, USA.
authors.forename: H
authors.initials: H
authors.lastname: Suzuki
authors.forename: D C
authors.initials: DC
authors.lastname: Poole
authors.forename: B W
authors.initials: BW
authors.lastname: Zweifach
authors.forename: G W
authors.initials: GW
authors.lastname: Schmid-Schönbein
mesh_terms: D000818:Animals; D016923:Cell Death; D002467:Cell Nucleus / Q000502:physiology / Q000648:ultrastructure; D004558:Electric Stimulation; D016166:Free Radical Scavengers / Q000494:pharmacology; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology; D007511:Ischemia / Q000503:physiopathology*; D007700:Kinetics; D008297:Male; D008433:Mathematics; D008564:Membrane Potentials; D008931:Mitochondria, Muscle / Q000187:drug effects / Q000502:physiology*; D008962:Models, Theoretical; D009119:Muscle Contraction / Q000187:drug effects; D018485:Muscle Fibers, Skeletal / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D015424:Reperfusion; D013482:Superoxide Dismutase / Q000494:pharmacology; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology; D013997:Time Factors
chemical_list: D016166:Free Radical Scavengers; C038983:1,3-dimethylthiourea; D013482:Superoxide Dismutase; D013890:Thiourea