title: 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 PaO2 (mmHg): normoxia (PaO2 = 80, n = 18), mild (PaO2 = 60, n = 10), moderate (PaO2 = 40, n = 12), moderately-severe (PaO2 = 30, n = 7) and severe (PaO2 = 20, n = 9). Arterial blood gases verified PaO2 and normal PaCO2 (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 mumol/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 mumol/g, P < 0.0001). Despite the reduction in LV adenosine triphosphate (ATP) with severe hypoxia (2.16 +/- 0.68 mumol/g, P < 0.05), CP was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Surgery, University of Toronto, Canada.
authors.forename: C
authors.initials: C
authors.lastname: Wittnich
authors.forename: S M
authors.initials: SM
authors.lastname: Torrance
mesh_terms: D000244:Adenosine Diphosphate / Q000032:analysis / Q000378:metabolism; D000249:Adenosine Monophosphate / Q000032:analysis / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000032:analysis / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism* / Q000502:physiology; D001784:Blood Gas Analysis; D006003:Glycogen / Q000032:analysis / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D007291:Inosine Monophosphate / Q000032:analysis / Q000378:metabolism; D007773:Lactates / Q000032:analysis / Q000378:metabolism; D008297:Male; D017202:Myocardial Ischemia / Q000378:metabolism* / Q000503:physiopathology; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010725:Phosphocreatine / Q000032:analysis / Q000378:metabolism; D012720:Severity of Illness Index; D013552:Swine; D013997:Time Factors
chemical_list: D007773:Lactates; D010725:Phosphocreatine; D007291:Inosine Monophosphate; D000249:Adenosine Monophosphate; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D006003:Glycogen