STUDIES OF HYPOXEMIC REOXYGENATION INJURY - WITHOUT AORTIC CLAMPING .2. EVIDENCE FOR REOXYGENATION DAMAGE/

This study tested the hypothesis that the developing heart is suscepti ble to oxygen-mediated damage after reintroduction of molecular oxygen and that this ''unintended'' reoxygenation injury causes lipid peroxi dation and functional depression that may contribute to perioperative cardiac dysfunction. Among 49 Duroc-Yorkshire piglets (2 to 3 weeks ol d, 3 to 5 kg) 15 control studies were done without hypoxemia to test t he effects of the surgical preparation (n = 10) and 60 minutes of card iopulmonary bypass (n = 5). Twenty-nine piglets underwent up to 2 hour s of ventilator hypoxemia (with inspired oxygen fraction reduced to 6% to 7%) to lower arterial oxygen tension to approximately 25 mm Hg. Fi ve piglets did not undergo reoxygenation to determine alterations caus ed by hypoxemia alone. Twenty-four others received reoxygenation by ei ther raising ventilator inspired oxygen fraction to 1.0 (n = 12) or in stituting cardiopulmonary bypass at oxygen tension 400 mm Hg (n = 12). Ventilator hypoxemia produced sufficient hemodynamic compromise and m etabolic acidosis that 18 piglets required premature reoxygenation (78 +/- 12 minutes), To avoid the influence of acidosis and hemodynamic d eterioration during ventilator hypoxemia, five others underwent 30 min utes of hypoxemia during cardiopulmonary bypass (circuit primed with b lood at oxygen tension 25 mm Hg) and 30 minutes of reoxygenation (oxyg en tension 400 mm Hg) during cardiopulmonary bypass. Biochemical marke rs of oxidant damage included measurement of coronary sinus and myocar dial conjugated dienes to determine lipid peroxidation and antioxidant reserve capacity assessed by incubating myocardial tissue in the oxid ant t-butylhydroperoxide. Functional recovery was determined by inscri bing pressure volume loops to determine end-systolic elastance and Sta rling curves by volume infusion, No biochemical or functional changes occurred in control piglets. Hypoxemia without reoxygenation did not c hange plasma levels of conjugated dienes, but lowered antioxidant rese rve capacity 24%, Reoxygenation by ventilator caused refractory ventri cular arrhythmias in two piglets (17% mortality), raised levels of con jugated dienes 45%, and reduced antioxidant reserve capacity 40% with recovery of 39% of mechanical function in the survivors. Comparable bi ochemical and functional changes occurred in piglets undergoing ventil ator hyperemia and/or cardiopulmonary bypass hypoxemia and reoxygenati on on cardiopulmonary bypass. We conclude that hypoxemia increases vul nerability to reoxygenation damage by reducing antioxidant reserve cap acity and that reoxygenation by either ventilator or cardiopulmonary b ypass produces oxidant damage with resultant functional depression tha t is not a result of cardiopulmonary bypass. These findings suggest th at initiation of cardiopulmonary bypass in cyanotic immature subjects causes an unintended reoxygenation injury, which may increase vulnerab ility to subsequent ischemia during surgical repair.