Cardiac function, myocardial glutathione, and matrix metalloproteinase-2 levels in hypoxic newborn pigs reoxygenated by 21%, 50%, or 100% oxygen

• Published in: Shock (Augusta, Ga.) Vol. 23; no. 4; p. 383
• Main Authors: Haase, Erika, Bigam, David L, Nakonechny, Quentin B, Rayner, David, Korbutt, Gregory, Cheung, Po-Yin
• Format: Journal Article
• Language: English
• Published: United States 01.04.2005
• Subjects: Animals; Animals, Newborn; Glutathione - metabolism; Hemodynamics; Hypertension, Pulmonary; Hypoxia; Matrix Metalloproteinase 2 - biosynthesis; Matrix Metalloproteinase 9 - biosynthesis; Myocardium - metabolism; Oxidative Stress; Oxygen - metabolism; Oxygen Inhalation Therapy - adverse effects; Oxygen Inhalation Therapy - methods; Random Allocation; Reperfusion; Swine; Time Factors
• ISSN: 1073-2322
• DOI: 10.1097/01.shk.0000158962.83529.ce

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.