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Leukocyte activation in ischemia-reperfusion injury of skeletal muscle
R A Cambria1, R J Anderson, G Dikdan
1Section of Vascular Surgery, University of Medicine and Dentistry of New Jersey, Newark 07103.
Abstract:
Polymorphonuclear leukocyte (PMN) participation in the pathophysiology of the reperfusion injury following skeletal muscle ischemia has become recognized. We measured the activation of PMNs as evidenced by production of superoxide anion (O2-) in the isolated canine gracilis muscle preparation of ischemia-reperfusion injury. PMNs were isolated from the gracilis muscle venous effluent and central venous blood after 6 hr of bilateral gracilis ischemia and 1 hr of reperfusion in five dogs. Baseline samples were obtained prior to ischemia from the central venous circulation. Liberation of O2- from PMNs and from PMNs stimulated by opsonized zymosan was determined by measuring ferricytochrome reduction. Results are expressed as nanomoles of O2- produced/2 x 10(6) PMN +/- SEM. O2- production by unstimulated cells was increased from 0.33 +/- 0.15 nmole in the baseline samples to 0.96 +/- 0.08 nmole in the central venous sample (P less than 0.01). With stimulation by zymosan, production increased from 10.3 +/- 1.4 nmole in the baseline samples to 15.2 +/- 1.1 nmole in the central venous sample (P less than 0.05) and to 15.5 +/- 0.9 nmole in the gracilis venous sample (P less than 0.01). These increases in superoxide production were not seen in the three sham-operated animals. Mean infarct size determined by planimetry was 55%. O2- produced by PMNs from central venous blood correlated with infarct size (r = 0.934, P = 0.02). These data imply that PMNs are activated by muscular ischemia, and the degree of activation is directly related to the extent of the muscle infarction.
Insights
Polymorphonuclear leukocytes (PMNs) show increased superoxide anion production after skeletal muscle ischemia-reperfusion injury. This PMN activation correlates with the severity of muscle infarction, highlighting their role in reperfusion injury.
Area of Science:
- Biomedical Science
- Physiology
- Immunology
Background:
- Polymorphonuclear leukocytes (PMNs) are increasingly recognized for their role in skeletal muscle ischemia-reperfusion (I/R) injury.
- Understanding PMN activation is crucial for mitigating reperfusion damage.
Purpose of the Study:
- To measure polymorphonuclear leukocyte (PMN) activation, specifically superoxide anion (O2-) production, in canine skeletal muscle during ischemia-reperfusion (I/R) injury.
- To investigate the correlation between PMN activation and the extent of muscle infarction.
Main Methods:
- Isolated canine gracilis muscle preparation subjected to 6 hours of ischemia and 1 hour of reperfusion.
- PMNs were isolated from gracilis venous effluent and central venous blood.
- Superoxide anion (O2-) production was measured using ferricytochrome reduction, both unstimulated and stimulated with opsonized zymosan.
Main Results:
- Unstimulated PMN O2- production significantly increased post-ischemia/reperfusion compared to baseline.
- Zymosan-stimulated PMN O2- production also showed significant increases in both central venous and gracilis venous samples.
- No increase in superoxide production was observed in sham-operated animals.
- Mean infarct size was 55%, and O2- production by PMNs from central venous blood strongly correlated with infarct size (r=0.934, P=0.02).
Conclusions:
- PMNs become activated following skeletal muscle ischemia.
- The degree of PMN activation is directly proportional to the extent of muscle infarction.
- These findings underscore the significant contribution of PMNs to the pathophysiology of skeletal muscle I/R injury.