Hyperglycaemia blocks sevoflurane-induced postconditioning in the rat heart in vivo: cardioprotection can be restored by blocking the mitochondrial permeability transition pore.
BACKGROUND
Recent studies showed that hyperglycaemia (HG) blocks anaesthetic-induced preconditioning. The influence of HG on anaesthetic-induced postconditioning (post) has not yet been determined. We investigated whether sevoflurane (Sevo)-induced postconditioning is blocked by HG and whether the blockade could be reversed by inhibiting the mitochondrial permeability transition pore (mPTP) with cyclosporine A (CsA).


METHODS
Chloralose-anaesthetized rats (n=7-11 per group) were subjected to 25 min coronary artery occlusion followed by 120 min reperfusion. Postconditioning was achieved by administration of 1 or 2 MAC sevoflurane for the first 5 min of early reperfusion. HG was induced by infusion of glucose 50% (G 50) for 35 min, starting 5 min before ischaemia up to 5 min of reperfusion. CsA (5 or 10 mg kg(-1)) was administered i.v. 5 min before the onset of reperfusion. At the end of the experiments, hearts were excised for infarct size measurements.


RESULTS
Infarct size (% of area at risk) was reduced from 51.4 (5.0)% [mean (sd)] in controls to 32.7 (12.8)% after sevoflurane postconditioning (Sevo-post) (P<0.05). This infarct size reduction was completely abolished by HG [51.1 (13.2)%, P<0.05 vs Sevo-post], but was restored by administration of sevoflurane with CsA [35.2 (5.2)%, P<0.05 vs HG+Sevo-post]. Increased concentrations of sevoflurane or CsA alone could not restore cardioprotection in a state of HG [Sevo-post2, 54.1 (12.6)%, P>0.05 vs HG+Sevo-post; CsA10, 58.8 (11.3)%, P>0.05 vs HG+CsA].


CONCLUSIONS
Sevoflurane-induced postconditioning is blocked by HG. Inhibition of the mPTP with CsA is able to reverse this loss of cardioprotection.
Huhn
R
R
Laboratory of Experimental Intensive Care and Anaesthesiology, Academic Medical Center, Department of Anaesthesiology, University of Amsterdam, Meibergdreef 9, 1100 DD Amsterdam, The Netherlands.
Heinen
A
A
Weber
N C
NC
Hollmann
M W
MW
Schlack
W
W
Preckel
B
B
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D016572:Cyclosporine / Q000494:pharmacology; D004334:Drug Administration Schedule; D006339:Heart Rate / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications*; D008297:Male; D008738:Methyl Ethers / Q000008:administration & dosage / Q000627:therapeutic use*; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000150:complications / Q000473:pathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
D001786:Blood Glucose; D002316:Cardiotonic Agents; D008738:Methyl Ethers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D000077149:Sevoflurane; D016572:Cyclosporine