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.

High Brain Tissue Oxygen Tension During Ventilation With 100% Oxygen After Fetal Asphyxia in Newborn Sheep

“…1). This is consistent with previous studies on the same asphyxia model (16) and with studies in asphyxiated 1-3-d-old piglets (23).…”

Resuscitation With 21% or 100% Oxygen Is Equally Effective in Restoring Perfusion and Oxygen Metabolism in the Liver of Hypoxic Newborn Piglets

“…The tachycardia compared with baseline observed in the 21% group after an hour of reoxygenation is not accompanied by changes in other hemodynamic parameters and did not differ from the other groups. Similar to another report (26), the significance of this transient tachycardia is uncertain. Thus, our results confirm that there is no advantage in using 100% over 21% oxygen in systemic hemodynamic recovery and acid-base balance in this model of severely asphyxiated newborn piglets.…”

“…The developmental differences in the response to H-R in the liver of neonates and adults are not known, whereas the neonatal heart may recover better from ischemia-reperfusion injury compared with the adult heart (31). We have previously used the newborn piglet model to describe the changes in other organs (11,17,26). Because of the liver`s dual blood supply and greater antioxidant content, we think that the hepatic responses are unique, as evidenced by the blunted overshooting of THFI and total hepatic DO 2 , contrasting to the dramatic changes in the mesenteric circulation upon reoxygenation (11,17).…”

Impaired Diastolic Function and Disruption of the Force-Frequency Relationship in the Right Ventricle of Newborn Pigs Resuscitated with 100% Oxygen

“…Myocardial oxidative stress, as seen with resuscitation with 100% oxygen measured by increased levels of oxidized glutathione, could therefore be an explanation for reduced diastolic function and myocardial damage with 100% oxygen [15] . Other authors have failed to demonstrate differences in cardiac troponin I, creatine kinase -myocardial band, myoglobin, glutathione and MMP-2 within groups of piglets resuscitated with 21, 50 or 100% oxygen [1,16] . In our study, however, cardiac troponin I increased in animals resuscitated with 100% oxygen compared to the room air group.…”

“…Another factor that could potentially contribute to enhanced cardiac output is the lowering effect of 100% oxygen on pulmonary vascular pressure. Previous data suggest that the decrease in pulmonary vascular pressure seen with 100% oxygen fails to increase cardiac output [16] . The overall non-difference between 100 and 21% reoxygenation in systemic hemodynamics and cardiac function during recovery in the studied period underscores that the changes found in this study are of possibly minor acute relevance only.…”