Reduction of reoxygenation injury and nitric oxide production in the cyanotic immature heart by controlling pO2.
Reintroduction of high levels of molecular oxygen after a hypoxic period is followed by a burst of nitric oxide (NO), peroxynitrite, and oxygen free radicals, which are highly cytotoxic. This study tests the hypotheses that a) controlled reoxygenation of cyanotic immature hearts when starting cardiopulmonary bypass (CPB) with high pO2 pressure of oxygen produces a reoxygenation injury, and b) this oxygen-related damage is avoidable by controlling the circumstances of the reoxygenation period (controlled reoxygenation). Of 40 immature piglets (2-3 weeks), 5 normoxic instrumented piglets served as control, and 6 underwent 1 h of CPB including 30 min of aortic clamping with blood cardioplegic (BCP) arrest without preceding hypoxia (BCP control). Twenty-nine others were made hypoxic (arterial pO2 20-30 mmHg) for up to 2 h by lowering the forced inspiratory oxygen (FiO2) on a ventilator. They were then reoxygenated on CPB as follows, 1) abrupt reoxygenation at pO2 400 mmHg in 5, (Reox), 2) gradual increase in pO2 from 30 to 400 mmHg in 5 (Graded Reox), both without BCP arrest, 3) starting CPB at different pO2 levels (hyperoxic, normoxic or hypoxic) for 5 min, followed by BCP arrest (Reox+BCP: pO2 > 400, 100 or 20-30 mmHg), in 19 others. Reoxygenation on CPB at pO2 more than 400 mmHg depressed contractility (endsystolic elastance [Ees] to 25 +/- 5% of control; P < 0.05), accompanied by reduced antioxidant reserve capacity [AORC] (P < 0.05 vs control), which was only slightly improved by Graded Reox (Ees 34 +/- 4%, P < 0.05 vs control).(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D000831:Animals, Newborn; D002315:Cardiopulmonary Bypass; D006324:Heart Arrest, Induced; D006330:Heart Defects, Congenital / Q000473:pathology / Q000503:physiopathology / Q000601:surgery*; D006439:Hemodynamics / Q000502:physiology; D015227:Lipid Peroxidation / Q000502:physiology; D009200:Myocardial Contraction / Q000502:physiology; D015428:Myocardial Reperfusion Injury / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D009569:Nitric Oxide / Q000097:blood*; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption / Q000502:physiology*; D010102:Oxygen Inhalation Therapy / Q000379:methods; D017382:Reactive Oxygen Species / Q000378:metabolism; D013552:Swine
D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D010100:Oxygen