The cardiovascular and 'systemic' effects of hyperoxia in the newborn.
Published: 2004
Language: eng
Number of pages: 199
Description: Piglets exposed to hyperoxia experienced significant reductions in contractility, systolic blood pressure and mean arterial blood pressure. In contrast heart rate was shown to significantly increase. LV SOD and GPx activities were both significantly reduced. RV SOD activity was significantly increased while significant reductions were seen in RV GPx activity after 5 hours of hyperoxia. LV MDA & 4HNE levels were significantly increased, while only MDA levels in the RV were shown to be elevated in piglets exposed to hyperoxia. An unexpected, rapid and sustained hyperglycemic response was seen throughout the 5 hour hyperoxic ventilatory period. A significant 2-fold elevation in plasma glucagon and a 3-fold elevation in insulin levels occurred, despite no significant changes in plasma epinephrine. Total GLUT1 and GLUT4 content were significantly reduced in skeletal muscle in piglets exposed to hyperoxia.Newborn children can be exposed to high oxygen levels (hyperoxia) for hours to days during their surgical and/or medical management. These patients also often have poor myocardial function and hemodynamics. Hyperoxia has toxic effects depending on the degree and duration of the exposure. Whether hyperoxia compromises myocardial function and hemodynamics in the newborn in the absence of any confounding variables remains essentially unexplored.Piglets were anesthetized, intubated and ventilated to normoxia. Once normal blood gases were confirmed, animals were randomly allocated to either 5 hours of normoxia or hyperoxia. Oxygen, blood glucose, plasma glucagon, insulin and epinephrine levels, myocardial functional and hemodynamic assessments were made. Left and right ventricular (LV & RV) biopsies were taken for measurements of antioxidant enzyme activities (Superoxide Dismutase-SOD, Glutathione Peroxidase-GPx and Catalase-CAT) as well as for malondialdehyde (MDA) and 4-Hydroxynonenal (4HNE) as indicators of oxygen free radical-mediated membrane injury. Total GLUT1 and GLUT4 content in cardiac and skeletal muscle was also measured using Western Blotting analysis.In the newborn, hyperoxia triggers oxygen free radical-mediated membrane injury together with an inability of the newborn heart to provide an adequate antioxidant enzyme defense while impairing myocardial function and hemodynamics. In addition, significant elevations in glucagon and reductions in total skeletal muscle GLUT1 and GLUT4 content all contributed to the hyperoxia-induced hyperglycemia.
Notes: Adviser:  Carin Wittnich.

Thesis (Ph.D.)--University of Toronto, 2004.

Electronic version licensed for access by U. of T. users.

Source: Dissertation Abstracts International, Volume: 65-10, Section: B, page: 5063.