Abstract 1003: Intermittent, Noromobaric Hypoxic Conditioning Is Cardio- And Vasoprotective In A Rat Model Of Myocardial Ischemia And Reperfusion
Intermittent hypoxic conditioning (IHC) may provide novel, non-invasive cardioprotection against ischemia-reperfusion (IR) damage. In the current study, rats were subjected to normobaric IHC (5 – 8 cycles/d for 20 days, FIO2 9.5 – 10% for 5 – 10 min/cycle, with intervening 4 min normoxia), a regimen that may have clinical applications. Control rats were sham-conditioned with 21% O2. In addition to parameters of cardioprotection, endothelial dysfunction was evaluated as an index of vasoprotective effects of IHC. Ischemia was produced in situ by ligation of the left coronary artery for 30 min, followed by 60-min reperfusion, while arrhythmias were monitored. Hearts were excised, perfused with Evans blue dye (area at risk, AAR) and then stained with triphenyltetrazolium chloride (infarct size, IS). AAR and IS were planimetrically measured, and IS was expressed as %AAR. Endothelium-dependent relaxation (EDR) was evaluated by the dilatory response to acetylcholine (10 μM) of norepinephrine (0.5 μM)-precontracted isolated aortic rings of control and IHC rats with and without IR. During ischemia, the durations of extrasystole (non-IHC: 16.6 ± 3.6 s, n = 14; IHC: 4.6 ± 2.0 s, n = 11) and ventricular tachycardia (non-IHC: 34.3 ± 8.0 s, n = 14; IHC: 2.5 ± 1.4 s, n = 11) were significantly reduced in IHC rats (P < 0.05), although reperfusion arrhythmias were not different. IHC decreased IS as %AAR by 43% (non-IHC: 30.3 ± 4.6%, n = 9; IHC: 17.5 ± 3.5%, n = 10, P < 0.05). EDR fell from 44.8 ± 4.2% in normal control rats (no IHC, no IR, n = 8) to 9.7 ± 1.2% in non-IHC rats with IR (n = 10, P < 0.001). IHC alone reduced pre-ischemic EDR to 33.9 ± 3.3% (n = 8, P < 0.05 vs. control), but completely prevented IR-induced endothelial dysfunction (29.9 ± 2.9% after IR in 10 IHC rats). In conclusion, moderate, intermittent, normobaric hypoxia conditioning is both cardio- and vasoprotective in a rat model of myocardial IR.