title: Reduced oxygen tension during cardiopulmonary bypass limits myocardial damage in acute hypoxic immature piglet hearts.
abstract: OBJECTIVE
  Cardiopulmonary bypass (CPB) is usually instituted in a hyperoxic fashion (oxygen tension (pO2) 300-500 mm Hg), which may expose cyanotic infants to potential reoxygenation damage. Oxygen free radicals play an important role in this injury. The rate of production of this highly reactive toxic oxygen species is dependent on the oxygen level during reoxygenation. This study tested the hypothesis that reduction of the oxygen in the bypass prime and in blood cardioplegia (BCP) to normoxic levels can reduce reoxygenation injury and will result in improved contractility.
  
  
  METHODS
  We operated on 19 Duroc-Yorkshire piglets (2-3 weeks, 3-5 kg). Five underwent 30 min of BCP arrest during 1 h of CPB without hypoxia (control). Fourteen underwent 120 min of hypoxia (arterial pO2 20-30 mmHg) on ventilator before reoxygenation on CPB. Reflecting the clinical routine procedure, nine of them were reoxygenated on CPB for 5 min with high pO2 (350-450 mm Hg) followed by 30 min of BCP arrest (high pO2) and 25 min of reoxygenation/reperfusion on CPB with high pO2 levels (NoRx). Five others were put on CPB with pO2 reduced to normoxic levels (pO2 100 mm Hg) in CPB and BCP (Rx). Functional and biochemical measurements were made before hypoxia, as well as during and after reoxygenation.
  
  
  RESULTS
  In contrast to controls, NoRx resulted in a 40% decrease in antioxidant reserve capacity (P<0.01) at 4 mM t-butyl hydroperoxide (t-BHP), a 1212% increase in myocardial conjugated diene production during BCP induction (P<0.0003), a 1000% during reperfusion (P<0.002), a 36.1% and a 37.0% increase in coronary sinus blood conjugated dienes at 35 min (P<0.05) and 60 min (P<0.05) of reoxygenation. These biochemical changes were accompanied by a 79% reduction of left ventricular contractility (P<0.0003). Conversely, Rx led to an improvement in antioxidant reserve capacity (939+/-212 vs. 1342+/-177 nmol/g protein; P<0.003), less conjugated diene production during BCP induction (15.5+/-6.1 vs. 42.1+/-8.8 A233 nm/min per 100 g; P<0.003) and reperfusion (1.8+/-3.9 vs 22.0+/-5.5 A233 nm/min per 100 g; P<0.005), and to a significantly improved post bypass LV contractility (58+/-25 vs. 21+/-5; P<0.0003).
  
  
  CONCLUSIONS
  These data document that hypoxemic/reoxygenation injury occurs in acute hypoxic immature piglet hearts when reoxygenated on CPB with hyperoxic pO2 (normal clinical practice). By lowering the antioxidant reserve capacity, hypoxemia seems to render the developing heart susceptible to reoxygenation damage, which occurs with the reintroduction of molecular oxygen, and is associated with free radical production, subsequent lipid peroxida tion, and depressed post bypass LV function. Reduction of pO2 during the initial reoxygenation period and during BCP arrest to normoxic levels resulted in a significant reduction of this oxygen-related damage and in much improved myocardial performance.
authors.affiliation: Department of Cardiothoracic Surgery, UCLA School of Medicine, Los Angeles, CA, USA.
authors.forename: K
authors.initials: K
authors.lastname: Ihnken
authors.forename: K
authors.initials: K
authors.lastname: Morita
authors.forename: G D
authors.initials: GD
authors.lastname: Buckberg
authors.forename: B
authors.initials: B
authors.lastname: Winkelmann
authors.forename: F
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: M P
authors.initials: MP
authors.lastname: Sherman
mesh_terms: D000208:Acute Disease; D000818:Animals; D001784:Blood Gas Analysis; D002315:Cardiopulmonary Bypass / Q000009:adverse effects; D004195:Disease Models, Animal; D006324:Heart Arrest, Induced / Q000009:adverse effects; D000860:Hypoxia / Q000097:blood*; D007432:Intraoperative Period; D015227:Lipid Peroxidation; D009200:Myocardial Contraction; D015428:Myocardial Reperfusion Injury / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D013552:Swine; D016277:Ventricular Function, Left / Q000502:physiology
chemical_list: D010100:Oxygen