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Experimental Biology and Medicine 231:802-805 (2006)
© 2006 Society for Experimental Biology and Medicine

VASCULAR AND HYPERTENSION

The Effect of Acute Ischemia on ET-1 and Its Receptors in Patients with Underlying Chronic Ischemia of the Lower Limb

Michael R. Dashwood*,1 and Janice C. S. Tsui{dagger}

* Clinical Biochemistry, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK; and {dagger} Department of Surgery, Southend Hospital, Prittlewell Chase, Southend-on-Sea, Essex SS0 0RY, UK

To whom requests for reprints should be addressed at 1 Clinical Biochemistry, Royal Free and University College Medical School, Royal Free Campus, Pond Street, London NW3 2QG, UK. E-mail: m.dashwood{at}medsch.ucl.ac.uk

Abstract

Elevated plasma and tissue endothelin (ET)-1 levels in patients with critical limb ischemia (CLI) has been described. Here the effect of a period of acute ischemia and subsequent reperfusion on plasma ET-1 and tissue ET-1/ET receptors in skeletal muscle biopsies from CLI patients undergoing femoro-distal bypass surgery was studied. Peripheral and "local" blood and muscle biopsies were obtained from patients undergoing femoro-distal bypass surgery, at the start of the procedure (control), after a period of vascular clamping (ischemia), and after clamp release (reperfusion). Plasma ET-1 was determined by enzyme-linked immunosorbent assay. Tissue ET-1 was assessed by counting ET-1 immunostaining cells per unit area, and ETA/ETB receptors were identified on sections by in vitro autoradiography in which binding was quantitatively assessed by densitometry. There was no significant effect of ischemia or reperfusion on plasma ET-1 levels or on ETA/ETB receptor binding. However, tissue ET-1 increased during both acute ischemia and reperfusion (P < 0.05). A high proportion of positive ET-1 immunostaining was associated with microvessels and also exhibited a similar distribution to macrophages. Previously, it has been shown that both plasma ET-1 and tissue ET-1/ET receptors are increased in CLI patients compared with atherosclerotic controls. Also, increased muscle ET-1 levels have been described in acute ischemia caused by tourniquet application in nonischemic patients undergoing total knee replacement. In CLI patients, in whom ET-1 is already upregulated, this further increase may exacerbate existing pathologic processes and contribute to ischemia-reperfusion injury. ET-1 antagonists may therefore be useful adjuncts in CLI and other surgical procedures in which ischemia-reperfusion damage occurs.

Key Words: ischemia • reperfusion • skeletal microvessels






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