Role of leukocyte accumulation and oxygen radicals in ischemia-reperfusion-induced injury in skeletal muscle.
The role of leukocytes and nonleukocyte-derived reactive oxygen metabolites (ROMs) in reperfusion-induced skeletal muscle injury was determined. Male rats received 2 h no-flow hindlimb ischemia-reperfusion (I/R, n = 6) or were rendered neutropenic via antineutrophil serum (ANS) before I/R (I/R + ANS, n = 5). Oxygen radicals in the absence of neutrophils were tested by administration of dimethylthiourea (DMTU) (I/R + ANS + DMTU, n = 5). Perfused capillaries (CD(per)) and rolling (L(r)), adherent (L(a)), and extravasated leukocytes (L(e)) in the extensor digitorum longus muscle were measured every 15 min during 90 min of reperfusion using intravital microscopy. The vital dyes bisbenzimide (BB) and ethidium bromide (EB) provided direct measures of tissue injury (EB/BB). CD(per) decreased immediately on reperfusion in the I/R and I/R + ANS groups. CD(per) in the I/R + ANS + DMTU group remained at baseline throughout reperfusion. L(a) increased in the I/R group; however, EB/BB was the same between I/R and I/R + ANS groups. Injury in the I/R + ANS + DMTU group did not differ from other groups > or =60 min, after which EB/BB became significantly lower. L(e) did not differ between groups and was highly correlated to tissue injury. The results suggest that L(e) lead to parenchymal injury, and ROMs lead to perfusion deficits during the early reperfusion period after ischemia.
Department of Medical Biophysics, University of Western Ontario, London, Ontario N6A 4G5, Canada.
M G
MG
Schlag
K A
KA
Harris
R F
RF
Potter
D000818:Animals; D002196:Capillaries / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D002467:Cell Nucleus / Q000473:pathology / Q000502:physiology; D006614:Hindlimb; D007106:Immune Sera / Q000494:pharmacology; D007511:Ischemia / Q000503:physiopathology*; D007962:Leukocytes / Q000502:physiology*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000473:pathology / Q000503:physiopathology*; D009504:Neutrophils / Q000502:physiology; D051381:Rats; D011920:Rats, Inbred WF; D017382:Reactive Oxygen Species / Q000502:physiology*; D015427:Reperfusion Injury / Q000503:physiopathology*; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology; D013997:Time Factors
D007106:Immune Sera; D017382:Reactive Oxygen Species; C038983:1,3-dimethylthiourea; D013890:Thiourea