Prevention of isoflurane-induced preconditioning by 5-hydroxydecanoate and gadolinium: possible involvement of mitochondrial adenosine triphosphate-sensitive potassium and stretch-activated channels.
BACKGROUND
Both mitochondrial adenosine triphosphate-sensitive potassium (MKATP) channels (selectively blocked by 5-hydroxydecanoate) and stretch-activated channels (blocked by gadolinium) have been involved in the mechanism of ischemic preconditioning. Isoflurane can reproduce the protection afforded by ischemic preconditioning. We sought to determine whether isoflurane-induced preconditioning may involve MKATP and stretch-activated channels.


METHODS
Anesthetized open-chest rabbits underwent 30 min of coronary occlusion followed by 3 h of reperfusion. Before this, rabbits were randomized into one of six groups and underwent a treatment period consisting of either no intervention for 40 min (control group; n = 9) or 15 min of isoflurane inhalation (1.1% end tidal) followed by a 15-min washout period (isoflurane group; n = 9). The two groups received an intravenous bolus dose of either 5-hydroxydecanoate (5 mg/kg) or gadolinium (40 micromol/kg) before coronary occlusion and reperfusion (5-hydroxydecanoate, n = 9; gadolinium, n = 7). Two additional groups received 5-hydroxydecanoate or gadolinium before isoflurane exposure (isoflurane-5-hydroxydecanoate, n = 10; isoflurane-gadolinium, n = 8). Area at risk and infarct size were assessed by blue dye injection and tetrazolium chloride staining.


RESULTS
Area at risk was comparable among the six groups (29 +/- 7, 30 +/- 5, 27 +/- 6, 35 +/- 7, 31 +/- 7, and 27 +/- 4% of the left ventricle in the control, isoflurane, isoflurane-5-hydroxydecanoate, 5-hydroxydecanoate, isoflurane-gadolinium, and gadolinium groups, respectively). Infarct size averaged 60 +/- 20% (SD) in untreated controls versus 54 +/- 27 and 65 +/- 15% of the risk zone in 5-hydroxydecanoate- and gadolinium-treated controls (P = nonsignificant). In contrast, infarct size in the isoflurane group was significantly reduced to 26 +/- 11% of the risk zone (P < 0.05 vs.control). Both 5-hydroxydecanoate and gadolinium prevented this attenuation: infarct size averaged 68 +/- 23 and 56 +/- 21% of risk zone in the isoflurane-5-hydroxydecanoate and isoflurane-gadolinium groups, respectively (P = nonsignificant vs.control).


CONCLUSIONS
5-Hydroxydecanoate and gadolinium inhibited pharmacologic preconditioning by isoflurane. This result suggests that MKATP channels and mechanogated channels are probably involved in this protective mechanism.
Piriou
V
V
Université Claude Bernard, Lyon, France. piriou@cismsun.univ-lyon1.fr
Chiari
P
P
Knezynski
S
S
Bastien
O
O
Loufoua
J
J
Lehot
J J
JJ
Foëx
P
P
Annat
G
G
Ovize
M
M
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D003652:Decanoic Acids / Q000494:pharmacology*; D005260:Female; D005682:Gadolinium / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006880:Hydroxy Acids / Q000494:pharmacology*; D019194:Ischemic Preconditioning; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008928:Mitochondria / Q000502:physiology*; D009203:Myocardial Infarction / Q000517:prevention & control; D015221:Potassium Channels / Q000502:physiology*; D011817:Rabbits; D013314:Stress, Mechanical
D003652:Decanoic Acids; D006880:Hydroxy Acids; D015221:Potassium Channels; C052853:5-hydroxydecanoic acid; D000255:Adenosine Triphosphate; D005682:Gadolinium; D007530:Isoflurane