title: The role of extracellular calcium in ischemia/reperfusion injury in skeletal muscle.
abstract: Ischemia-reperfusion injury to skeletal muscle, following an acute arterial occlusion is a significant cause of morbidity and mortality. The purpose of this study is to examine the role of extracellular calcium in the production of cellular necrosis following a prolonged period of normothermic ischemia. Bilateral canine gracilis muscles were made ischemic for 4.5 to 5 hr. The control muscle had normal blood reperfusion (ionized Ca2+ 1.2 mM). The treated muscle was perfused for 30 min with an oxygenated solution (ionized Ca2+ 0.11 mM) containing free radical scavengers followed by normal blood perfusion. Necrosis was determined by nitroblue tetrazolium staining after 48 hr of reperfusion. Total muscle Ca2+ was measured by atomic absorption spectrometry. Pre- and postischemic muscle Ca2+ levels were similar (2.8 +/- 0.4 vs 3.2 +/- 0.8 nmole/mg protein, n = 13, P greater than 0.1). After 30 min of reperfusion the treated muscle Ca2+ was 2.4 +/- 0.4 compared to control levels of 8.6 +/- 0.8 nmole/mg protein (P less than 0.001). Total tissue calcium returned to normal at 60 min in viable muscle, but continued to accumulate in necrotic tissue. However, the delay in initial muscle Ca2+ influx was not associated with increased overall salvage of muscle 78 +/- 9% vs 77 +/- 8% necrosis, (P greater than 0.1). In conclusion we could not demonstrate a protective effect of reduced extracellular Ca2+ during early reperfusion, and it negated our previously demonstrated beneficial effects of free radical scavengers. It was shown however that the early ability to extrude intracellular calcium was associated with significant salvage of muscle tissue.
authors.affiliation: Department of Clinical Biochemistry, R. Fraser Elliott Vascular Research Laboratory, Toronto General Hospital, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Smith
authors.forename: G
authors.initials: G
authors.lastname: Hayes
authors.forename: A
authors.initials: A
authors.lastname: Romaschin
authors.forename: P
authors.initials: P
authors.lastname: Walker
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology*; D004285:Dogs; D005110:Extracellular Space / Q000378:metabolism*; D007511:Ischemia / Q000473:pathology*; D009132:Muscles / Q000098:blood supply* / Q000473:pathology; D009336:Necrosis; D015427:Reperfusion Injury / Q000473:pathology*
chemical_list: D002118:Calcium