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 Skeletal Muscle Ischemia and Reperfusion: Mechanisms of Injury and Intervention

Skeletal muscle energy metabolism

  • Normal skeletal muscle energy metabolism.
  • Skeletal muscle energy metabolism during ischemia.
  • Skeletal muscle energy metabolism during reperfusion.

Tissue injury in skeletal muscle ischemia/reperfusion

  • Histology.
  • Methods of assessment.

Pathophysiology of skeletal muscle ischemia/reperfusion

  • Endogenous free radical production by postischemic endothelial cells.
  • Recruitment and activation of neutrophils wielding free radicals and lytic enzymes (including the role of complement, arachidonic acid metabolites, platelet activating factor, cytokines, cell adhesion molecules).
  • Occlusion of microvascular beds secondary to endothelial cell swelling, perivascular tissue edema, failed endothelium-dependent vessel relaxation, adherence of activated neutrophils and microvascular thrombosis).

Interventional outline

  • Metabolic salvage.
  • Inhibition of free radical production during reperfusion.
  • Graded reoxygenation during reperfusion.
  • Leukopenic reperfusion.
  • Hypothermia during reperfusion.
  • Fibrinolysis, anticoagulation.


Defraigne JO, Pincemail J. Local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. Physiopathology and prevention. Acta Chir Belg 1998;98:176-186.

This article analyzes the local and systemic consequences of severe ischemia and reperfusion of the skeletal muscle. The mechanisms responsible for reperfusion injury as well as methods of prevention and treatment are also discussed.

Duran WN, Takenaka H, Hobson RW 2nd. Microvascular pathophysiology of skeletal muscle ischemia-reperfusion. Semin Vasc Surg 1998;11:203-214.

This article reviews the pivotal role of endothelium-leukocyte interactions and of cytokines in the genesis of postischemic damage in muscle. Clinical considerations and future directions based on research and practice are presented.

Gute DC , Ishida T, Yarimizu K, Korthuis RJ. Inflammatory responses to ischemia and reperfusion in skeletal muscle. Mol Cell Biochem 1998;179:169-187.

This article describes the cytologic and biochemical responses of skeletal muscle to ischemia and reperfusion injury. It is also discussed how an endogenous protective mechanism, ischemic preconditioning, may be exploited to limit postischemic skeletal muscle injury.

Rubin BB, Romaschin A, Walker PM, Gute DC, Korthuis RJ. Mechanisms of postischemic injury in skeletal muscle: intervention strategies. J Appl Physiol 1996;80:369-387.

This article reviews the mechanisms involved in the pathogenesis of skeletal muscle ischemia-reperfusion injury including oxidant generation, elaboration of proinflammatory mediators, infiltration of leukocytes, Ca2+ overload, phospholipid peroxidation and depletion, impaired nitric oxide metabolism, and reduced ATP production. Based on these mechanisms, rational intervention strategies may be proposed and implemented as potential treatments for skeletal muscle dysfunction associated with ischemia-reperfusion.

Pang CY, Forrest CR, Mounsey R. Pharmacologic intervention in ischemia-induced reperfusion injury in the skeletal muscle. Microsurgery 1993;14:176-182.

This article provides a concise review on the potential causes of ischemia-induced reperfusion injury and pharmacologic intervention in the skeletal muscle. The mechanism of ischemic preconditioning and its clinical applications for augmentation of skeletal muscle tolerance to prolonged ischemic insult are also discussed.

Posted June 2010