title: Normobaric, intermittent hypoxia conditioning is cardio- and vasoprotective in rats.
abstract: Favorable versus detrimental cardiovascular responses to intermittent hypoxia conditioning (IHC) are heavily dependent on experimental or pathological conditions, including the duration, frequency and intensity of the hypoxia exposures. Recently, we demonstrated that a program of moderate, normobaric IHC (FIO2 9.5-10% for 5-10 min/cycle, with intervening 4 min normoxia, 5-8 cycles/day for 20 days) in dogs afforded robust cardioprotection against infarction and arrhythmias induced by coronary artery occlusion-reperfusion, but this protection has not been verified in other species. Accordingly, in this investigation cardio- as well as vasoprotection were examined in male Wistar rats completing the normobaric IHC program or a sham program in which the rats continuously breathed atmospheric air. Myocardial ischemia and reperfusion (IR) was imposed by occlusion and reperfusion of the left anterior descending coronary artery in in situ experiments and by subjecting isolated, perfused hearts to global ischemia-reperfusion. Cardiac arrhythmias and myocardial infarct size were quantified in in situ experiments. Endothelial function was evaluated from the relaxation to acetylcholine of norepinephrine-precontracted aortic rings taken from in situ IR experiments, and from the increase in coronary flow produced by acetylcholine in isolated hearts. IHC sharply reduced cardiac arrhythmias during ischemia and decreased infarct size by 43% following IR. Endothelial dysfunction in aorta was marked after IR in sham rats, but not significant in IHC rats. Similar findings were found for the coronary circulations of isolated hearts. These findings support the hypothesis that moderate, normobaric IHC is cardio- and vasoprotective in a rat model of IR.
authors.affiliation: Laboratory of Adaptation, Institute for General Pathology and Pathophysiology, Moscow 125315, Russian Federation.
authors.forename: Eugenia B
authors.initials: EB
authors.lastname: Manukhina
authors.forename: Ludmila M
authors.initials: LM
authors.lastname: Belkina
authors.forename: Olga L
authors.initials: OL
authors.lastname: Terekhina
authors.forename: Denis V
authors.initials: DV
authors.lastname: Abramochkin
authors.forename: Elena A
authors.initials: EA
authors.lastname: Smirnova
authors.forename: Olga P
authors.initials: OP
authors.lastname: Budanova
authors.forename: Robert T
authors.initials: RT
authors.lastname: Mallet
authors.forename: H Fred
authors.initials: HF
authors.lastname: Downey
mesh_terms: D000818:Animals; D001011:Aorta / Q000502:physiology / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D000860:Hypoxia / Q000503:physiopathology*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology / Q000517:prevention & control; D015425:Myocardial Reperfusion; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
keywords: Acetylcholine; aorta; coronary circulation; myocardial infarction; myocardial ischemia and reperfusion; nitric oxide