Ischaemic preconditioning reduced infarct size to 14.8% of the risk region versus 39.8% in controls, but this protection was reversed by coadministration of glibenclamide (31.3%).
Does glibenclamide reverse the infarct-limiting effect of ischemic preconditioning in a rabbit model of ischemia-reperfusion?
The infarct-limiting effect of ischemic preconditioning in rabbits is reversed by glibenclamide, indicating the involvement of ATP-sensitive potassium channels.
Absolute Event Rate: 31.3% vs 14.8%
OBJECTIVE: The aim was to determine whether ischaemic preconditioning occurs through the actions of ATP sensitive potassium (KATP) channels during ischaemia and whether pharmacological antagonism of these channels can reverse the protective effect of preconditioning. METHODS: 31 New Zealand White rabbits were instrumented for coronary occlusion and reperfusion. Control animals were subjected to ischaemia (30 min) and reperfusion (120 min) only. Study animals were divided into three experimental groups: (1) those receiving intravenous glibenclamide (0.3 mg.kg-1) prior to the 30 min ischaemia; (2) those receiving 5 min preconditioning ischaemia and 10 min reperfusion prior to the 30 min ischaemia; or (3) those receiving preconditioning in the presence of glibenclamide prior to the 30 min ischaemia. The resulting infarct and myocardium at risk were visualised with Indian ink and tetrazolium staining and quantified using computer assisted planimetry. RESULTS: Rabbits which were preconditioned showed a 63% reduction in infarct size 14.8(SEM 2.2)% of risk region in comparison to non-preconditioned controls 39.8(2.1)%. When rabbits were preconditioned in the presence of glibenclamide the protection was reversed 31.3(5.1)% using a dose of glibenclamide which by itself did not alter necrosis 37.7(5.4)%. CONCLUSIONS: Infarct size reduction in the rabbit via ischaemic preconditioning is reversible with the coadministration of glibenclamide.
Toombs et al. (1993) studied Myocardial infarction (n=31). Glibenclamide during ischaemic preconditioning vs. Ischaemic preconditioning alone was evaluated on Infarct size (% of risk region). Ischaemic preconditioning reduced infarct size to 14.8% of the risk region versus 39.8% in controls, but this protection was reversed by coadministration of glibenclamide (31.3%).