title: Gender and post-ischemic recovery of hypertrophied rat hearts.
abstract: BACKGROUND
  Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. However, it is unknown if post-ischemic function or metabolism of female hypertrophied hearts differ from male hypertrophied hearts. Thus, we tested the hypothesis that gender influences post-ischemic function of pressure-overload hypertrophied hearts and determined if the effect of gender on post-ischemic outcome could be explained by differences in metabolism, especially the catabolic fate of glucose.
  
  
  METHODS
  Function and metabolism of isolated working hearts from sham-operated and aortic-constricted male and female Sprague-Dawley rats before and after 20 min of no-flow ischemia (N = 17 to 27 per group) were compared. Parallel series of hearts were perfused with Krebs-Henseleit solution containing 5.5 mM [5-3H/U-14C]-glucose, 1.2 mM [1-14C]-palmitate, 0.5 mM [U-14C]-lactate, and 100 mU/L insulin to measure glycolysis and glucose oxidation in one series and oxidation of palmitate and lactate in the second. Statistical analysis was performed using two-way analysis of variance. The sequential rejective Bonferroni procedure was used to correct for multiple comparisons and tests.
  
  
  RESULTS
  Female gender negatively influenced post-ischemic function of non-hypertrophied hearts, but did not significantly influence function of hypertrophied hearts after ischemia such that mass-corrected hypertrophied heart function did not differ between genders. Before ischemia, glycolysis was accelerated in hypertrophied hearts, but to a greater extent in males, and did not differ between male and female non-hypertrophied hearts. Glycolysis fell in all groups after ischemia, except in non-hypertrophied female hearts, with the reduction in glycolysis after ischemia being greatest in males. Post-ischemic glycolytic rates were, therefore, similarly accelerated in hypertrophied male and female hearts and higher in female than male non-hypertrophied hearts. Glucose oxidation was lower in female than male hearts and was unaffected by hypertrophy or ischemia. Consequently, non-oxidative catabolism of glucose after ischemia was lowest in male non-hypertrophied hearts and comparably elevated in hypertrophied hearts of both sexes. These differences in non-oxidative glucose catabolism were inversely related to post-ischemic functional recovery.
  
  
  CONCLUSIONS
  Gender does not significantly influence post-ischemic function of hypertrophied hearts, even though female sex is detrimental to post-ischemic function in non-hypertrophied hearts. Differences in glucose catabolism may contribute to hypertrophy-induced and gender-related differences in post-ischemic function.
authors.affiliation: James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Department of Pathology and Laboratory Medicine, University of British Columbia-St Paul's Hospital, Vancouver, BC, V6Z 1Y6, Canada. rsaeedi@mrl.ubc.ca
authors.forename: Ramesh
authors.initials: R
authors.lastname: Saeedi
authors.forename: Richard B
authors.initials: RB
authors.lastname: Wambolt
authors.forename: Hannah
authors.initials: H
authors.lastname: Parsons
authors.forename: Christine
authors.initials: C
authors.lastname: Antler
authors.forename: Hon S
authors.initials: HS
authors.lastname: Leong
authors.forename: Angelica
authors.initials: A
authors.lastname: Keller
authors.forename: George A
authors.initials: GA
authors.lastname: Dunaway
authors.forename: Kirill M
authors.initials: KM
authors.lastname: Popov
authors.forename: Michael F
authors.initials: MF
authors.lastname: Allard
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D006321:Heart / Q000503:physiopathology*; D008297:Male; D017202:Myocardial Ischemia / Q000503:physiopathology*; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012737:Sex Factors
chemical_list: D005947:Glucose