Isoflurane and sevoflurane during reperfusion prevent recovery from ischaemia in mitochondrial KATP channel blocker pretreated hearts.
OBJECTIVE
Inhalation anaesthetics given only during post-ischaemic reperfusion have some protective effect against reperfusion injury in the heart. Adenosine triphosphate-regulated mitochondrial potassium channels have been shown to be an important mediator of cardioprotection. Thus, we investigated whether 5-hydroxydecanoate, a putative mitochondrial potassium channel blocker, prevents the cardioprotective effect of volatile anaesthetics.


METHODS
Forty rats were randomly allocated to four groups of equal size: control group, 5-hydroxydecanoate group, 5-hydroxydecanoate + sevoflurane group and 5-hydroxydecanoate + isoflurane group. Seven minutes after the start of perfusion, normal saline (control group) or 5-hydroxydecanoate (the other groups) was administered. Ten minutes after the start of perfusion, the heart was rendered globally ischaemic for 10 min. One minute before the end of the ischaemic period, 2.7% sevoflurane or 1.4% isoflurane were administered in the 5-hydroxydecanoate + sevoflurane or 5-hydroxydecanoate + isoflurane groups respectively. The heart was reperfused for 10 min.


RESULTS
Adenosine triphosphate content at the end of reperfusion in the 5-hydroxydecanoate + sevoflurane group was significantly lower (P < 0.05) than those in the control and the 5-hydroxydecanoate + isoflurane groups (19.9 +/- 8.7, 28.1 +/- 3.4 and 30.4 +/- 2.3 micromol g(-1), respectively). In addition, the combination of inhalation anaesthetics and 5-hydroxydecanoate decreased the ratios of recovered hearts from ischaemia (5-hydroxydecanoate + sevoflurane group: 40%, 5-hydroxydecanoate + isoflurane group 50%).


CONCLUSIONS
5-hydroxydecanoate alone caused no significant changes in haemodynamics and myocardial metabolism. However, the combination of 5-hydroxydecanoate and volatile anaesthetics impaired the recovery from ischaemia. Although animal data cannot be extrapolated to human beings, we suggest that more attention be paid to patients on sulphonylurea drugs, which inhibit potassium channels, when they are anaesthetized with volatile anaesthetics.
Masui
K
K
University of Yamanashi, Faculty of Medicine, Department of Anesthesiology, Yamanashi, Japan. kenichi@masuinet.com
Kashimoto
S
S
Furuya
A
A
Oguchi
T
T
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology*; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D008929:Mitochondria, Heart / Q000187:drug effects*; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000503:physiopathology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane
D018685:Anesthetics, Inhalation; D003652:Decanoic Acids; D006880:Hydroxy Acids; D008738:Methyl Ethers; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C117780:mitochondrial K(ATP) channel; D000077149:Sevoflurane; C052853:5-hydroxydecanoic acid; D007530:Isoflurane