Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore.
BACKGROUND
Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP.


METHODS
Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 micromol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 micromol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area).


RESULTS
Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48+/-2.70)% vs (48.47+/-6.03)%, P<0.05; PPC vs CTRL: (35.60+/-2.10)% vs (48.47+/-6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48+/-2.70)% vs (35.60+/-2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol.


CONCLUSIONS
Postconditioning of sevoflurane and propofol has cardioprotective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.
He
Wei
W
Department of Anesthesiology, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
Zhang
Feng-jiang
FJ
Wang
Shao-ping
SP
Chen
Gang
G
Chen
Cong-cong
CC
Yan
Min
M
D000758:Anesthesia; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D006321:Heart / Q000187:drug effects*; D006439:Hemodynamics; D019157:Ischemic Preconditioning, Myocardial; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D010477:Perfusion; D015742:Propofol / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013778:Tetrazolium Salts / Q000494:pharmacology
D018685:Anesthetics, Inhalation; D008738:Methyl Ethers; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D013778:Tetrazolium Salts; D000077149:Sevoflurane; C009591:triphenyltetrazolium; D007770:L-Lactate Dehydrogenase; D015742:Propofol