COMPLEMENT INHIBITORS IN MYOCARDIAL ISCHEMIA REPERFUSION INJURY/

Myocardial ischemia/reperfusion injury is accompanied by an inflammato ry response contributing to reversible and irreversible changes in tis sue viability and organ function. Endothelial and leukocyte responses are involved in tissue injury, orchestrated primarily by the complemen t cascade. Anaphylatoxins, and assembly of the membrane attack complex contribute directly and indirectly to further tissue damage. Tissue s alvage can be achieved by depletion of complement components, thus mak ing evident a contributory role for the complement cascade in ischemia /reperfusion injury. The complexity of the complement cascade provides numerous sites as potential targets for therapeutic interventions des igned to modulate the complement response to injury. The latter is exe mplified by the ability of a soluble form of complement receptor 1 (sC R1) to decrease infarct size in in vivo models of ischemia/reperfusion injury as well as prevent myocyte and vascular injury and organ dysfu nction by interdicting assembly of the membrane attack complex. Effect ive inhibitors of complement are not limited to newly developed compou nds or solubilized forms of endogenous regulators of complement activa tion. Therapeutic agents in common use, such as heparin and related no n-anticoagulant glycosaminoglycans, are known to inhibit the complemen t activation in vitro as well as in vivo and may prove useful as cytop rotective agents. (C) 1997 Elsevier Science B.V.