title: Sex differences in newborn myocardial metabolism and response to ischemia.
abstract: In children with congenital heart disease, female sex has been linked to greater in-hospital mortality associated with low cardiac output, yet the reasons for this are unclear. Therefore, we examined whether newborn sex differences in the heart's metabolic response to ischemia exist. Left ventricular (LV) in vivo and ischemic biopsies of newborn male and female piglets were compared. Tissue ATP, creatine phosphate (CP), glycogen, anaerobic end-products lactate and hydrogen ion (H), and key regulatory enzymes were measured. Compared with males, newborn females displayed 14% lower ATP, 22% lower CP, and 32% lower glycogen reserves (p < 0.05) at baseline. During ischemia, newborn females accumulated 17% greater lactate and 40% greater H accumulation (p < 0.02), which was associated with earlier cessation of glycolysis and lower ischemic ATP levels (p < 0.02) compared with males. Newborn females demonstrated a greater ability to use their glycogen reserves, resulting in significantly lower (p < 0.003) glycogen levels throughout the ischemic period. Thus, newborn females are at a metabolic disadvantage because they exhibited lower energy levels and greater tissue lactic acidosis, both linked to an increase susceptibility to ischemic injury and impair myocardial function on reperfusion.
authors.affiliation: Department of Physiology, University of Toronto, Toronto, Ontario M5S 1A8, Canada. c.wittnich@utoronto.ca
authors.forename: Carin
authors.initials: C
authors.lastname: Wittnich
authors.forename: Danny
authors.initials: D
authors.lastname: Quaglietta
authors.forename: Luke
authors.initials: L
authors.lastname: Tan
authors.forename: Michael P
authors.initials: MP
authors.lastname: Belanger
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D004734:Energy Metabolism / Q000502:physiology*; D005260:Female; D005470:Fluorometry; D006003:Glycogen / Q000378:metabolism; D006352:Heart Ventricles / Q000378:metabolism*; D007511:Ischemia / Q000378:metabolism*; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010725:Phosphocreatine / Q000378:metabolism; D011522:Protons; D012737:Sex Factors; D034421:Sus scrofa
chemical_list: D011522:Protons; D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D006003:Glycogen