Isoflurane inhaled at the onset of reperfusion potentiates the cardioprotective effect of ischemic postconditioning through a NO-dependent mechanism.
Postconditioning (PCD) is known to reduce infarct size (IS). Here, we investigated whether isoflurane, which is known to potentiate preconditioning, also potentiates PCD and whether NO is involved. Accordingly, open-chest rabbits underwent 30-minute coronary artery occlusion (CAO) followed by 3-hour coronary artery reperfusion (CAR). In control and postconditioned (4 cycles of 30s-CAR/30s-CAO after the 30-min CAO), rabbits were anesthetized with pentobarbital alone or in combination with isoflurane inhaled (i) throughout the experiment or (ii) only during CAR. With pentobarbital alone, PCD significantly reduced IS versus control (39 +/- 7% vs. 55 +/- 4% of the risk zone, respectively, P < 0.05). Isoflurane--0.5% throughout the experiment did not alter IS in both control and PCD groups. Isoflurane--2% throughout the experiment reduced IS in control (37 +/- 8%, P < 0.05 vs. pentobarbital alone) and enhanced the protective effect of PCD (IS = 21 +/- 3%, P < 0.05 vs. both control and PCD under pentobarbital alone). When isoflurane--2% was administered only during reperfusion, IS was not changed in control (53 +/- 3%) but combination with PCD reduced IS to 23 +/- 4% (P < 0.05 vs. both control and PCD under pentobarbital alone). L-arginine analog N-nitro-L-arginine methyl ester administered before reperfusion did not properly alter IS (53 +/- 6%) but abolished the effect of PCD alone (IS = 47 +/- 7%) or in combination with isoflurane--2% during reperfusion (55 +/- 3%). Thus, isoflurane potentiates PCD at reperfusion through a NO-dependent mechanism.
Tessier-Vetzel
Dominique
D
INSERM U 660, Université Paris XII, Créteil, France.
Tissier
Renaud
R
Waintraub
Xavier
X
Ghaleh
Bijan
B
Berdeaux
Alain
A
D000280:Administration, Inhalation; D018685:Anesthetics, Inhalation / Q000008:administration & dosage*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D019157:Ischemic Preconditioning, Myocardial; D007530:Isoflurane / Q000008:administration & dosage*; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009569:Nitric Oxide / Q000502:physiology*; D011817:Rabbits
D018685:Anesthetics, Inhalation; D009569:Nitric Oxide; D007530:Isoflurane