title: Cardiac function, myocardial glutathione, and matrix metalloproteinase-2 levels in hypoxic newborn pigs reoxygenated by 21%, 50%, or 100% oxygen.
abstract: After asphyxia, it is standard to resuscitate the newborn with 100% oxygen, which may create a hypoxia-reoxygenation process that may contribute to subsequent myocardial dysfunction. We examined the effects of graded reoxygenation on cardiac function, myocardial glutathione levels, and matrix metalloproteinase (MMP)-2 activity during recovery. Thirty-two piglets (1-3 days old, weighing 1.5-2.1 kg) were anesthetized and instrumented for continuous monitoring of cardiac index, and systemic and pulmonary arterial pressures. After 2 h of hypoxia, piglets were randomized to receive reoxygenation for 1 h with 21%, 50%, or 100% oxygen (n = 8 each), followed by 3 h at 21% oxygen. At 2 h of hypoxemia (PaO2 32-34 mmHg), the animals had hypotension, decreased cardiac index, and elevated pulmonary arterial pressure (P < 0.001 vs. controls). Upon reoxygenation, cardiac function recovered in all groups with higher cardiac index and lower systemic vascular resistance in the 21% group at 30 min of reoxygenation (P < 0.05 vs. controls). Pulmonary artery pressure normalized in an oxygen-dependent fashion (100% = 50% > 21%), despite an immediate recovery of pulmonary vascular resistance in all groups. The hypoxia-reoxygenated (21%-100%) hearts had similarly increased MMP-2 activity and decreased glutathione levels (P < 0.05, 100% vs. controls), which correlated significantly with cardiac index and stroke volume during reoxygenation, and similar features of early myocardial necrosis. In neonatal resuscitation, if used with caution because of a slower resolution of pulmonary hypertension, 21% reoxygenation results in similar cardiac function and early myocardial injury as 50% or 100%. The significance of higher oxidative stress with high oxygen concentration is unknown, at least in the acute recovery period.
authors.affiliation: Departments of Surgery, University of Alberta Hospital, Edmonton, Alberta, Canada T6G 2B7.
authors.forename: Erika
authors.initials: E
authors.lastname: Haase
authors.forename: David L
authors.initials: DL
authors.lastname: Bigam
authors.forename: Quentin B
authors.initials: QB
authors.lastname: Nakonechny
authors.forename: David
authors.initials: D
authors.lastname: Rayner
authors.forename: Gregory
authors.initials: G
authors.lastname: Korbutt
authors.forename: Po-Yin
authors.initials: PY
authors.lastname: Cheung
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D005978:Glutathione / Q000378:metabolism*; D006439:Hemodynamics; D006976:Hypertension, Pulmonary; D000860:Hypoxia; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis*; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009206:Myocardium / Q000378:metabolism*; D018384:Oxidative Stress; D010100:Oxygen / Q000378:metabolism*; D010102:Oxygen Inhalation Therapy / Q000009:adverse effects* / Q000379:methods*; D011897:Random Allocation; D015424:Reperfusion; D013552:Swine; D013997:Time Factors
chemical_list: D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D005978:Glutathione; D010100:Oxygen