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The role of the endothelium for reperfusion injury

J. Pernow*, A.T. Gonon and A. Gourine

Department of Cardiology, Karolinska Hospital, Stockholm, Sweden

* Correspondence: John Pernow, MD, PhD, Department of Cardiology, Karolinska Hospital, S-171 76 Stockholm, Sweden.

Abstract

Reperfusion following myocardial ischaemia induces a rapid change in endothelial function. Endothelium-dependent vasodilatation is impaired due to attenuated production of nitric oxide (NO) and/or enhanced inactivation of NO by superoxide. In addition, production of the vasoconstrictor peptide endothelin is increased. This results in a change from a state of vasorelaxation in the normal situation to an increased vasoconstrictor tone following reperfusion. There is a marked infiltration of neutrophils into the jeopardized myocardium during early reperfusion, which contributes to cell death. The adhesion of neutrophils to the endothelium is mediated by cell adhesion molecules which are expressed on endothelial cells, vascular smooth muscle cells and neutrophils during reperfusion. The reduction in NO bioavailability during early reperfusion contributes to several events in the reperfusion injury. Therefore, maintenance of NO levels is important for protection against reperfusion injury. Administration of the NO substrate L-arginine or NO donors in connection with reperfusion attenuates neutrophil accumulation and reduces infarct size. Furthermore, blockade of adhesions molecules reduces the extent of reperfusion injury. Endothelin also seems to be of importance for the development of reperfusion injury. Endothelin receptor antagonists improve endothelial and ventricular function and reduce infarct size following ischaemia and reperfusion. The mechanism behind the cardioprotective effect of endothelin receptor antagonists seems to involve inhibition of neutrophil-mediated injury and NO production. The endothelium plays an important role during the development of reperfusion injury. The reperfusion injury is reduced by enhancing NO levels, blocking endothelin receptors and inhibiting neutrophil adhesion.

Key Words: Endothelium • reperfusion • nitric oxide • endothelin • neutrophils

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