Effects of nicorandil on myocardial function and metabolism in the post-ischaemic reperfused heart with or without inhalation anaesthetics.
BACKGROUND
Nicorandil, which is an ATP-sensitive K channel opener, has been reported to protect the ischaemic myocardium. However, its interaction with inhalation anaesthetics on the ischaemic myocardium has not been well elucidated. So, we have investigated whether isoflurane or sevoflurane modify the effects of nicorandil on cardiac function and metabolism in the rat heart-lung preparation.


METHODS
Animals were allocated to 4 groups as follows: Control group, no drug; Nic group, nicorandil; Nic+Iso group, nicorandil and isoflurane; Nic+Sev group, nicorandil and sevoflurane. Seven minutes after the start of perfusion, nicorandil was administered and 10 min after the start of perfusion, the heart was rendered globally ischaemic for 10 min, and then the heart was reperfused for 10 min.


RESULTS
LVdP/dt max in the Nic group was higher than those in the other groups. Right atrial pressure in the Nic+Iso and Nic+Sev groups was significantly higher than in the Control and Nic groups. Myocardial ATP in the Nic group was higher than in the other groups. DHBA levels in the perfusate in the Nic and Nic+Iso groups were lower than those in the Control and Nic+Sev groups, but those in the Nic+Sev group were higher than those in the other groups.


CONCLUSIONS
Nicorandil improved post-ischaemic cardiac function and preserved high-energy phosphates. However, these beneficial effects of nicorandil were abolished by the combination with isoflurane or sevoflurane. In addition, sevoflurane increased hydroxyl radical formation in the post-ischaemic reperfused heart.
Furuya
A
A
Department of Anaesthesiology, Yamanashi Medical University, Yamanashi, Japan.
Kashimoto
S
S
Kumazawa
T
T
D000255:Adenosine Triphosphate / Q000378:metabolism; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D005841:Gentisates / Q000378:metabolism; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D015425:Myocardial Reperfusion; D009206:Myocardium / Q000378:metabolism*; D020108:Nicorandil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D014665:Vasodilator Agents / Q000494:pharmacology*
D018685:Anesthetics, Inhalation; D005841:Gentisates; D008738:Methyl Ethers; D015221:Potassium Channels; D014665:Vasodilator Agents; D020108:Nicorandil; D000077149:Sevoflurane; D000255:Adenosine Triphosphate; D007530:Isoflurane