title: Acute intermittent hypoxia improves rat myocardium tolerance to ischemia.
abstract: In this study, we investigated the influence of depth and duration of intermittent hypoxia (IH) on the infarct size development in isolated rat heart. The role of nitric oxide synthase (NOS) and ATP-sensitive K+ (K(ATP)) channel was also studied. Wistar male rats were exposed to IH [repetitive cycles of 1 min, 40 s with inspired oxygen fraction (FI(O2)), 5 or 10%, followed by 20-s normoxia], during 30 min or 4 h. Another group was exposed to 4 h of continuous hypoxia with 10% FI(O2). Twenty-four hours later, their hearts were isolated and subjected to a 30-min no-flow global ischemia-120-min reperfusion sequence. For some hearts, N(omega)-nitro-L-arginine methyl ester (L-NAME) (a nonselective inhibitor of NOS) or 5-hydroxydecanoic acid (5-HD) (a selective mitochondrial K(ATP) blocker) was infused before ischemia. Infarct size (in percentage of ventricles) was significantly reduced by prior IH for 4 h (10% FI(O2)) (21.8 +/- 3.1 vs. 33.5 +/- 2.5% in sham group). This effect was abolished by L-NAME or 5-HD. Infarct size was not different in groups subjected to either 30 min of IH or to continuous hypoxia compared with sham group. In contrast, IH for 4 h (5% FI(O2)) significantly increased infarct size (45.1 +/- 3.6 vs. 33.5 +/- 2.5% in sham group). Acute IH for 4 h with a minimal FI(O2) of 10% induced a delayed preconditioning against myocardial infarction in the rat, which was abolished by NOS inhibition and mitochondrial K(ATP) channel blockade. Depth, duration, and intermittence of hypoxia appeared to be critical for cardioprotection to occur.
authors.affiliation: Laboratoire HP2, Hypoxie Physiopathologie Respiratoire et Cardiovasculaire, EA3745, ESPRI INSERM, Faculté de Médecine-Pharmacie, Université Grenoble I, Domaine de la Merci, 38706 La Tronche Cedex, France.
authors.forename: P C
authors.initials: PC
authors.lastname: Béguin
authors.forename: M
authors.initials: M
authors.lastname: Joyeux-Faure
authors.forename: D
authors.initials: D
authors.lastname: Godin-Ribuot
authors.forename: P
authors.initials: P
authors.lastname: Lévy
authors.forename: C
authors.initials: C
authors.lastname: Ribuot
mesh_terms: D000208:Acute Disease; D000818:Animals; D004198:Disease Susceptibility / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000503:physiopathology* / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications / Q000503:physiopathology* / Q000628:therapy*; D016896:Treatment Outcome