Noninvasive Monitoring to Demonstrate Postoperative Differences in Regional Hemodynamics in Newborn Infants With d-Transposition of the Great Arteries and Hypoplastic Left Heart Syndrome.

BACKGROUND: The adequacy of tissue O2 delivery in infants receiving intensive care is difficult to measure directly. Regional O2 (rSO2) and fractional tissue O2 extraction (FTOE), the ratio of O2 consumption to O2 delivery, obtained from newer noninvasive tools, such as near-infrared spectroscopy (INVOS) and microvascular tissue oximetry (T-Stat) can provide important information on the adequacy of tissue oxygenation and aid in managing critically ill infants. METHODS: We prospectively evaluated differences in rSO2 and FTOE in 26 infants with hypoplastic left heart syndrome (HLHS) (n = 12) or d-transposition of the great arteries (d-TGA) (n = 14). Continuous noninvasive monitoring of SpO2, heart rate, and perfusion index with pulse oximetry, cerebral-rSO2 and renal-rSO2 with INVOS, and buccal tissue oxygenation using T-Stat were performed during immediate postoperative period for 24 hours. RESULTS: The SpO2 and rSO2 in infants with d-TGA were higher compared with the infants with HLHS at all measured sites (buccal mucosa, cerebral, and renal). Significant regional differences were also observed in FTOE across all infants with the highest at the buccal mucosa tissue level, followed by cerebral and renal measurement sites. As compared with infants with d-TGA, infants with HLHS had higher regional FTOE and heart rate, with a lower arterial O2 content and perfusion index. CONCLUSIONS: Our study demonstrates the utility of noninvasive hemodynamic monitoring to assess regional oxygenation and perfusion, as evidenced by significant differences in infants with HLHS and d-TGA, conditions with different circulation physiologies. Such comprehensive monitoring can potentially aid in evaluating treatment strategies aimed at preventing organ damage from O2 insufficiency.

Krebs cycle metabolites and preferential succinate oxidation following neonatal hypoxic-ischemic brain injury in mice.

BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H2O2 generation rate in the ischemic brain.ResultsWhile brain mitochondria from control mice exhibited a rotenone-sensitive complex-I-dependent respiration, HI-brain mitochondria, at the initiation of reperfusion, demonstrated complex-II-dependent respiration, as rotenone minimally affected, but inhibition of complex-II ceased respiration. This was associated with a 30-fold increase of cerebral succinate concentration and significantly elevated H2O2 emission rate in HI-mice compared to controls. At 60 min of reperfusion, cerebral succinate content and the mitochondrial response to rotenone did not differ from that in controls.ConclusionThese data are the first ex vivo evidence, that at the initiation of reperfusion, brain mitochondria transiently shift their metabolism from complex-I-dependent oxidation of NADH toward complex II-linked oxidation of succinate. Our study provides a critical piece of support for existence of the RET-dependent mechanism of elevated ROS production in reperfusion.