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Angiology
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Altered Endothelin-1 Levels in Acute Lower Limb Ischemia and Reperfusion

J. C. S. Tsui, MRCS

Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, UK, jcstsui{at}hotmail.com

D. M. Baker, FRCS

Department of Surgery, Royal Free and University College Medical School, Royal Free Campus, London, UK

E. Biecker, MD

Department of Clinical Pharmacology, University Hospital, Bern, Switzerland

S. Shaw, PhD

Department of Clinical Research, University Hospital, Bern, Switzerland

M. R. Dashwood, PhD, FASA

Department of Clinical Biochemistry, Royal Free and University College Medical School, Royal Free Campus, London, UK

Tourniquet-induced ischemia is often used in orthopedic and reconstructive procedures. This is associated with muscle damage and dysfunction, which limits tourniquet application time. Endothelin-1 (ET-1) is a potent vasoconstrictor, which has been implicated in ischemic conditions and ischemia-reperfusion injury. This study aimed to investigate the role of ET-1 in human skeletal muscle subjected to tourniquet-induced acute ischemia and reperfusion. Thirteen patients undergoing total knee replacement were studied. Plasma and muscle ET-1 concentrations were measured at the start of surgery, after an hour of acute ischemia, and 15 minutes following reperfusion. ET-1 receptor binding was also studied by use of autoradiography, and ET-1 mRNA expression investigated by use of real-time polymerase chain reaction (RT-PCR). Tissue ET-1 increased following the period of acute ischemia and persisted during reperfusion. ET-1 was associated with microvessels and macrophages in the muscle. No changes in circulating ET-1 levels, ET-1 mRNA expression, or ET-1 receptor binding were found. It is concluded that the ET-1 pathway is involved in acute ischemia and reperfusion and it may contribute to the muscle injury that occurs during surgical procedures.

Angiology, Vol. 55, No. 5, 533-539 (2004)
DOI: 10.1177/000331970405500509
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M. R. Dashwood and J. C. S. Tsui
The Effect of Acute Ischemia on ET-1 and Its Receptors in Patients with Underlying Chronic Ischemia of the Lower Limb.
Experimental Biology and Medicine, June 1, 2006; 231(6): 802 - 805.
[Abstract] [Full Text] [PDF]


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