Role of neutrophil-endothelial adhesion in skeletal muscle reperfusion injury

Abstract

During postischaemic revascularization neutrophil-endothelial adhesion in the skeletal muscle microcirculation, promoted by the neutrophil adhesion molecule Mac-1, may impair muscle blood flow and release oxygen free radicals and proteolytic enzymes which causes further tissue injury. This study has assessed the effect of an anti-Mac-1 monoclonal antibody on the severity of skeletal muscle injury in a rat model of 6-h hindlimb ischaemia and 4-h reperfusion. In control animals a sustained impairment of muscle perfusion was associated with neutrophil sequestration, muscle infarction and muscle oedema (P < 0.001 versus normal rats). In contrast, intravenous administration of anti-Mac-1 monoclonal antibody before revascularization prevented neutrophil recruitment, reduced muscle necrosis and improved postischaemic muscle perfusion at 120 and 240 min (not significantly different from normal), thus confirming that neutrophils are important cellular mediators of skeletal muscle reperfusion injury. Monoclonal antibodies targeting neutrophil adhesion molecules may, therefore, have a role in the prevention of this complication of limb revascularization.

Prevention of postischemic tissue injury by controlled reperfusion: A preliminary study

“…Various reperfusion techniques have been developed to modify or prevent the reperfusion damage, such as the limb washout technique using a roller pump [37], axillo-bifemoral grafting with intermittent perfusion of the lower limbs to control subsequent hyperkalemia [40], or the use of an oxygenator to reperfuse ischemic tissue [48]. In addition, numerous pathophysiological mechanisms and pharmacological treatments have been advocated for the management of reperfusion injury after acute limb ischemia, including steroids, lazaroids, barbiturates, papaverine, pentoxifylline, leukocyte-antibodies and radical scavenger just to mention a few [4,8,10,14,16,[20][21][22]24,32,33,39,44]. However, a stable reperfusion protocol has not evolved and the treatment of ischemiaperfusion of the lower limbs still consists in surgical revascularization, fasciotomy, excision of primary necrotic tissue, increase of urine output with urine alkalinization, treatment of hyperkalemia and, recently, the development of interventional treatment, e.g., for aortic saddle thrombus consisting in angioplasty and streptokinase 1 application [2,25].…”

The role of glycine in regulated cell death

“…Infusion of glycine at the end of 6 hours of skeletal muscle ischemia and then during the first hour of reperfusion decreased necrosis and increased metabolic and functional recovery [242]. Glycine suppression of reactive oxygen species production by neutrophils [165] may have played a major role in this skeletal muscle effect [243]. …”

The inflammatory response: friend or enemy for muscle injury?: Figure 1

“…23 Animals rendered leucopenic develop less damage and less oxidant production during the reperfusion phase. 24 On the basis of the observed time course for neutrophil infiltration and degree of injury, 7 the hypothesis that neutrophils play a role in stretch injury has been investigated. Using an antibody that blocks the neutrophil's respiratory burst, it has been shown that the degree of myofibre damage can be considerably reduced 24 hours after injury.…”