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INTERNATIONAL ANGIOLOGY

A Journal on Angiology


Official Journal of the International Union of Angiology, the International Union of Phlebology and the Central European Vascular Forum
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International Angiology 2001 June;20(2):174-80

Copyright © 2002 EDIZIONI MINERVA MEDICA

language: English

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


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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. ThiBack­ground. 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.s study sup­ports the hypoth­e­sis that cro­mak­a­lim reduc­es postischaem­ic skel­e­tal mus­cle dam­age and reper­fu­sion inju­ry.

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