BJA Advance Access originally published online on July 22, 2005
British Journal of Anaesthesia 2005 95(4):442-447; doi:10.1093/bja/aei203
CARDIOVASCULAR |
Isoflurane does not mimic ischaemic preconditioning in decreasing hydroxyl radical production in the rabbit
1 Departments of Anesthesiology and Critical Care Medicine and 2 Cellular Biochemistry and Human Genetics, Hadassah-Hebrew University Medical Center, Jerusalem, Israel
* Corresponding author: Department of Anesthesiology and CCM, Hadassah University Hospital, Jerusalem 91120, Israel. E-mail: gozaly{at}md.huji.ac.il
Background. Reactive oxygen species are an important mediator in isoflurane-induced myocardial preconditioning. However, hydroxyl radicals are also released during reperfusion after regional ischaemia. The purpose of the present study was to test whether ischaemic preconditioning and isoflurane would influence the production of hydroxyl radicals during reperfusion.
Methods. After i.v. administration of salicylate 100 mg kg–1 and a 30 min stabilization period, New Zealand White rabbits were subjected to 40 min of regional myocardial ischaemia and 2 h of reperfusion. Ischaemic preconditioning was elicited by 5 min ischaemia followed by 10 min reperfusion (before the 40 min ischaemia). In another group, isoflurane (2.1%) was administered for 30 min, followed by 15 min washout, before the long ischaemia. Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining. We quantified the level of OH-mediated conversion of salicylate to its dihydrobenzoate derivatives (2,3- and 2,5-DHBAs). Normalized values of the DHBAs (ng DHBA per mg salicylate) were calculated.
Results. Mean (SE) infarct size was 57 (6)% of the risk area in the untreated controls. This was significantly smaller in the ischaemic preconditioning and isoflurane groups: 22 (5) and 23 (6)% respectively. At 10 min of reperfusion, ischaemic preconditioning limited the mean increase in 2,3-DHBA to 24% from baseline, compared with 81% in control and 74% in the isoflurane group. Normalized 2,5-DHBA was maximally increased by 75% in the untreated group, 4 min after reperfusion. Ischaemic preconditioning significantly inhibited this increase (24% increase from baseline, P<0.01). However, the increase observed in the isoflurane group was not different from control (71%).
Conclusions. As already known, ischaemic preconditioning and isoflurane markedly reduced infarct size. However, only ischaemic preconditioning decreased postischaemic production of hydroxyl radicals. These different effects suggest different protective mechanisms at the cellular level.