Studies of hypoxemic/reoxygenation injury: Without aortic clamping

Abstract

This study tested the hypothesis that the developing heart is susceptible to oxygen-mediated damage after reintroduction of molecular oxygen and that this "unintended" reoxygenation injury causes lipid peroxidation and functional depression that may contribute to perioperative cardiac dysfunction. Among 49 Duroc-Yorkshire piglets (2 to 3 weeks old, 3 to 5 kg) 15 control studies were done without hypoxemia to test the effects of the surgical preparation (n = 10) and 60 minutes of cardiopulmonary bypass (n = 5). Twenty-nine piglets underwent up to 2 hours of ventilator hypoxemia (with inspired oxygen fraction reduced to 6% to 7%) to lower arterial oxygen tension to approximately 25 mm Hg. Five piglets did not undergo reoxygenation to determine alterations caused by hypoxemia alone. Twenty-four others received reoxygenation by either raising ventilator inspired oxygen fraction to 1.0 (n = 12) or instituting cardiopulmonary bypass at oxygen tension 400 mm Hg (n = 12). Ventilator hypoxemia produced sufficient hemodynamic compromise and metabolic acidosis that 18 piglets required premature reoxygenation (78 +/- 12 minutes). To avoid the influence of acidosis and hemodynamic deterioration during ventilator hypoxemia, five others underwent 30 minutes of hypoxemia during cardiopulmonary bypass (circuit primed with blood at oxygen tension 25 mm Hg) and 30 minutes of reoxygenation (oxygen tension 400 mm Hg) during cardiopulmonary bypass. Biochemical markers of oxidant damage included measurement of coronary sinus and myocardial conjugated dienes to determine lipid peroxidation and antioxidant reserve capacity assessed by incubating myocardial tissue in the oxidant t-butylhydroperoxide. Functional recovery was determined by inscribing pressure volume loops to determine end-systolic elastance and Starling curves by volume infusion. No biochemical or functional changes occurred in control piglets. Hypoxemia without reoxygenation did not change plasma levels of conjugated dienes, but lowered antioxidant reserve capacity 24%. Reoxygenation by ventilator caused refractory ventricular arrhythmias in two piglets (17% mortality), raised levels of conjugated dienes 45%, and reduced antioxidant reserve capacity 40% with recovery of 39% of mechanical function in the survivors. Comparable biochemical and functional changes occurred in piglets undergoing ventilator hypoxemia and/or cardiopulmonary bypass hypoxemia and reoxygenation on cardiopulmonary bypass. We conclude that hypoxemia increases vulnerability to reoxygenation damage by reducing antioxidant reserve capacity and that reoxygenation by either ventilator or cardiopulmonary bypass produces oxidant damage with resultant functional depression that is not a result of cardiopulmonary bypass. These findings suggest that initiation of cardiopulmonary bypass in cyanotic immature subjects causes an unintended reoxygenation injury, which may increase vulnerability to subsequent ischemia during surgical repair.

Postischemic Reperfusion Injury Can Be Attenuated by Oxygen Tension Control

“…15 Resynthesis of ATP is delayed because of hypoxia during hypoxic reperfusion. 19 The finding that ATP levels are significantly depressed and ventricular function decreases during hypoxia parallel the findings seen clinically. 16 Excessive hypoxia during reperfusion may thus also result in poor recovery from ischemic injury.…”

“…16 Excessive hypoxia during reperfusion may thus also result in poor recovery from ischemic injury. 19 The experimental model used in our study has several limitations. First, we used a crystalloid solution in the perfusion circuit.…”

Controlled reoxygenation cardiopulmonary bypass is associated with reduced transcriptomic changes in cyanotic tetralogy of Fallot patients undergoing surgery

“…The immature heart has a higher tolerance to hypoxia, but preceding hypoxia prior to ischemic cardioplegic arrest results in poor functional recovery and is associated with derangements in several metabolites (19,23). Hypoxia also reduces the antioxidant reserve capacity, leading to a greater susceptibility to the oxidative stress of ischemia (e.g., cross-clamping of the aorta) and reoxygenation (12,18,38). Re-introduction of oxygen exacerbates this situation and eventually leads to a reduction in myocardial contractility (1,12,13,16,18,38).…”

“…Reoxygenation injury is associated with the production of reactive oxygen species by the formation of oxygen-derived free radicals such as superoxide and peroxide. This leads to cell membrane degradation through lipid peroxidation (12,18). It is now evident that oxidative stress is a major part of the cellular mechanism of the resulting myocardial damage (3,10,30,35).…”

Change in the Membranous Lipid Composition Accelerates Lipid Peroxidation in Young Rat Hearts Subjected to 2 Weeks of Hypoxia Followed by Hyperoxia

“…Hypoxia per se does not raise the myocardial lipid peroxidation level, as shown in both our and other studies. 28,29 Ihnken et al reported that hypoxia increases cardiac susceptibility to oxidant damage by reducing antioxidants, and re-oxygenation further depletes the antioxidant level and accelerates lipid peroxidation. 28 Lipid peroxidation occurs by oxidation of PUFA in microsomal phospholipids.…”