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Rivista di Angiologia
Official Journal of the , the International Union of Phlebology and the
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
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International Angiology 2001 Giugno;20(2):174-80
The effect of pretreatment with ischaemic preconditioning or cromakalim on perfusion in skeletal muscle during ischaemia-reperfusion injury
Seifalian A. M., Chaloupka K. *, Lohn J. W., Gürke L. *, Heberer M. *, Hamilton G.
From the Vascular Haemodynamic Laboratory, University Department of Surgery, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London, UK
* Department for Surgical Research, University Hospital of Basel, Basel, Switzerland
Background. Ischaemia-induced damage of skeletal muscle may lead to side effects in orthopaedic and reconstructive surgery where tourniquet ischaemia is applied to ensure a bloodless operative field. In this study we investigated the effect of ischaemia-reperfusion injury with and without preconditioning by studying the skeletal muscle microcirculation. A further aim was to establish whether ischaemic preconditioning or pretreatment with cromakalim, a potassium channel opener reduces ischaemia-reperfusion injury.
Methods. Twenty-eight Wistar rats were randomised into four groups (n=7 per group). Group 1, control with no treatment; Group 2, two and a half hours tourniquet ischaemia followed by two hours of reperfusion to the left hindlimb. Furthermore, we pre-treated two groups prior to the ischaemia-reperfusion period; Group 3 with three short cycles of ischaemia-reperfusion (5’/5’) and Group 4 pre treated with cromakalim (100 µg/kg bw). We monitored the gastrocnemius muscle blood flow in vivo.
Results. There were no significant changes in the skeletal muscle microcirculation and temperature at the baseline in the four groups (p=0.110). In the ischaemic reperfusion, ischaemia preconditioning and cromakalim groups, the recorded skeletal muscle microcirculation during ischaemia decreased significantly (p<0.001) with respect to the baseline. In Group 2 the microcirculation recovered rapidly after release of the tourniquet, but was significantly lower (37% of baseline value, p<0.001) within two hours of reperfusion. In the ischaemia preconditioning group the microcirculation as in the ischaemia-reperfusion group recovered rapidly after release of the tourniquet, although failing to reach the baseline value within two hours of reperfusion. The mean microcirculation value of the left limb was slightly higher than Group 2 but significantly lower compared to the baseline after two hours of reperfusion (p<0.001). The change in the skeletal muscle microcirculation with cromakalim after two hours of reperfusion was not significant when compared to baseline values (p>0.05). The cromakalim group after two hours reperfusion had significantly higher microcirculation values when compared with Groups 2 and 3 (p<0.001). During ischaemia-reperfusion in Groups 2-4, there was no significant alteration in the systemic haemodynamic circulation.
Conclusions. This study supports the hypothesis that cromakalim reduces postischaemic skeletal muscle damage and reperfusion injury.