title: The effect of pretreatment with ischaemic preconditioning or cromakalim on perfusion in skeletal muscle during ischaemia-reperfusion injury.
abstract: 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 microg/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 percent 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.
authors.affiliation: Vascular Haemodynamic Laboratory, University Department of Surgery, Royal Free and University College Medical School, University College London and The Royal Free Hospital, London, UK. a.seifalian@rfc.ucl.ac.uk
authors.forename: A M
authors.initials: AM
authors.lastname: Seifalian
authors.forename: K
authors.initials: K
authors.lastname: Chaloupka
authors.forename: J W
authors.initials: JW
authors.lastname: Lohn
authors.forename: L
authors.initials: L
authors.lastname: Gürke
authors.forename: M
authors.initials: M
authors.lastname: Heberer
authors.forename: G
authors.initials: G
authors.lastname: Hamilton
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D019806:Cromakalim / Q000627:therapeutic use*; D005121:Extremities / Q000098:blood supply; D019157:Ischemic Preconditioning, Myocardial; D017078:Laser-Doppler Flowmetry; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D023421:Models, Animal; D008955:Models, Cardiovascular; D018482:Muscle, Skeletal / Q000098:blood supply / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000628:therapy*; D010477:Perfusion; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects
chemical_list: D000959:Antihypertensive Agents; D019806:Cromakalim