BACKGROUND AND AIMS: Hyperglycaemia blocks sevoflurane-induced postconditioning, 
and cardioprotection in hyperglycaemic myocardium can be restored by inhibition 
of the mitochondrial permeability transition pore (mPTP). We investigated 
whether sevoflurane-induced postconditioning is also blocked in the prediabetic 
heart and if so, whether cardioprotection could be restored by inhibiting mPTP.
METHODS AND RESULTS: Zucker lean (ZL) and Zucker obese (ZO) rats were assigned 
to one of seven groups. Animals underwent 25 min of ischaemia and 120 min of 
reperfusion. Control (ZL-/ZO Con) animals were not further treated. 
postconditioning groups (ZL-/ZO Sevo-post) received sevoflurane for 5 min 
starting 1min prior to the onset of reperfusion. The mPTP inhibitor cyclosporine 
A (CsA) was administered intravenously in a concentration of 5 (ZO CsA and ZO 
CsA+Sevo-post) or 10 mg/kg (ZO CsA10+Sevo-post) 5 min before the onset of 
reperfusion. At the end of reperfusion, infarct sizes were measured by TTC 
staining. Blood samples were collected to measure plasma levels of insulin, 
cholesterol and triglycerides. Sevoflurane postconditioning reduced infarct size 
in ZL rats to 35±12% (p<0.05 vs. ZL Con: 60±6%). In ZO rats sevoflurane 
postconditioning was abolished (ZO Sevo-post: 59±12%, n.s. vs. ZO Con: 58±6%). 5 
mg and 10 mg CsA could not restore cardioprotection (ZO CsA+Sevo-post: 59±7%, ZO 
CsA10+Sevo-post: 57±14%; n.s. vs. ZO Con). In ZO rats insulin, cholesterol and 
triglyceride levels were significant higher than in ZL rats (all p<0.05).
CONCLUSION: Inhibition of mPTP with CsA failed to restore cardioprotection in 
the prediabetic but normoglycaemic heart of Zucker obese rats in vivo.