Limitations of ischemic tolerance in oxidative skeletal muscle: Perfusion vs tissue protection

Amit Badhwar, Alison A. Dungey, Kenneth A. Harris, Jeremy A. Scott, Sarah D. McCarter, Jeffery R. Scott, Thomas L. Forbes, Richard F. Potter

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Objective. This study determined if ischemic tolerance occurs in oxidative skeletal muscle following a severe ischemia/reperfusion (I/R) insult and if such protection involves the induction of nitric oxide synthase (NOS). Methods. The soleus muscle of male Wistar rats (250-350 g) was preconditioned (PC + I/R) using five cycles of ischemia (10 min) and reperfusion (10 min) or had no PC (I/R) and 24 h later 2 h no-flow ischemia was induced. Calcium dependent (cNOS) and independent (iNOS) NOS activities were determined from PC (n = 5), or sham (n = 5) and the role of iNOS was tested by application of aminoguanidine (AMG) (100 μM; n = 4) to the muscle bath. Direct measures of the number of perfused capillaries (Npc; #/mm) during 90-min reperfusion were obtained using intravital microscopy. Tissue injury was estimated using the fluorescent vital dyes ethidium bromide (E; labels injured cells) and bisbenzimide (B; labels all cells) and expressed as the ratio E/B. Results. PC prevented microvascular flow deficits (Npc:I/R = 23.4 ± 1.3 vs PC + I/R = 29.9 ± 1.1) and resulted in a modest, but significant reduction (21%) in tissue injury (I/R = 0.82 ± 0.03 vs PC + I/R = 0.64 ± 0.04). PC led to a nine fold increase in iNOS activity, but decreased cNOS activity by 94% compared to sham. AMG prevented the parenchymal protection following PC, but had no effect on microvascular perfusion. Conclusion. Ischemic tolerance, 24 h following PC, preserved microvascular perfusion, but only modestly improved tissue viability in the soleus muscle.

Original languageEnglish
Pages (from-to)62-67
Number of pages6
JournalJournal of Surgical Research
Issue number1
StatePublished - Jan 2003
Externally publishedYes


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