Does the Severity of Acute Hypoxia Influence Neonatal Myocardial Metabolism and Sensitivity to Ischemia?

Abstract

The level of systemic hypoxia required to alter neonatal myocardial metabolism and its resultant effect on tolerance to global ischemia is unknown. This study examines myocardial purine nucleotides, glycogen (MG), lactate, creatine phosphate (CP) and the subsequent tolerance to ischemia in hearts exposed to varying levels of hypoxia (2 h). Three-day-old swine were randomly allocated into five study groups. Animals were anaesthetized and ventilated (2 h) with varying mixtures of medical air and nitrogen to achieve their target PaO 2 (mmHg); normoxia (PaO 2 = 80, n = 18), mild (PaO 2 = 60, n = 10), moderate (PaO 2 = 40, n = 12), moderately-severe (PaO 2 = 30, n = 7) and severe (PaO 2 = 20, n = 9). Arterial blood gases verified PaO 2 and normal PaCO 2 (39.5 ± 0.5 mmHg). Subsequently, the heart was exposed and the metabolic profile determined from a freeze-clamp LV biopsy. The heart was excised and tolerance to ischemia determined by time (min) to ischemic contracture onset (TICo) and peak (TICp). The results demonstrated a tendency to decreased MG with progressive hypoxia which reached significance in severe hypoxia (6.6 ± 2.7 μmol/g. P <0.05). Despite a doubling of myocardial lactate with moderately-severe hypoxia, increases only reached significance with severe hypoxia (27.8 ± 6.3 μmol/g, P<0.0001). Despite the reduction in LV adenosine triphosphate (ATP) with severe hypoxia (2.16 ± 0.68 μmol/g, P<0.05). CP was unaltered. The slightly (13%) depressed ischemic tolerance with all levels of hypoxia only reached significance with severe hypoxia (TICo = 11.3 ± 2.2 P<0.0001 and TICp = 27.4 ± 3.1, P<0.05). From normoxia to moderately-severe hypoxia (2 h), neonatal myocardial metabolism and tolerance to ischemia were not significantly altered. With a slight further PaO 2, reduction, hearts had significantly altered metabolism and decreased ischemic tolerance.