Role of heparin in reducing skeletal muscle infarction in ischemia-reperfusion.
Heparin continues to be recommended in the clinical management of limb ischemia to prevent extension of distal vascular thrombosis and increased rates of limb loss. However, heparin may also be responsible for reduced skeletal muscle injury. Although its mechanism of action has not been fully evaluated, we have investigated the ability of heparin to minimize skeletal muscle injury associated with the ischemia-reperfusion syndrome in an in vivo canine gracilis muscle model. Our findings demonstrated a significant reduction in the amount of skeletal muscle infarction, microvascular permeability, and H+ ion accumulation cumulation after preischemic heparinization. Diffuse intravascular coagulation also has been observed in observed in this model which may be prevented or reduced by the anticoagulant properties of heparin when administered prior to ischemia. However, heparin's protective effect may be independent of its anticoagulant activity. Heparin is a polycomponent drug with non-anticoagulant properties which may serve to reduce cellular injury during ischemia and reperfusion in several different ways. Microvascular injury is decreased by the restoration of normal intimal negative charge and through the binding and resultant inactivation of histamine, bradykinin and other vasoactive amines. Heparin inhibits the complement cascade which is known to determine ischemic infarct size. Other factors of importance in determining the extent of skeletal injury include neutrophil activation, chemotaxis, enzyme release, and free oxygen radical generation, all of which are decreased or modulated by heparin. Heparin is a complex substance and much more remains to be learned about its anticoagulant and nonanticoagulant properties as well as its protective effects on skeletal muscle injury in ischemia-reperfusion syndrome.
Hobson
R W
RW
Department of Surgery, UMDNJ-New Jersey Medical School 07103-2757.
Neville
R
R
Watanabe
B
B
Canady
J
J
Wright
J G
JG
Belkin
M
M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use; D004285:Dogs; D005260:Female; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use*; D006614:Hindlimb / Q000098:blood supply; D000960:Hypolipidemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007238:Infarction / Q000209:etiology / Q000517:prevention & control*; D007511:Ischemia / Q000150:complications; D008297:Male; D009132:Muscles / Q000098:blood supply*; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000960:Hypolipidemic Agents; D006493:Heparin