Abstract
BackgroundGender 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.MethodsFunction 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.ResultsFemale 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.ConclusionGender 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.
Highlights
Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels
Despite having a beneficial effect on cardiac remodelling due to hemodynamic overload, female sex is associated with greater rates of heart failure in the presence of symptomatic coronary artery disease [7,8]
The presence of left ventricular hypertrophy has been shown to have a detrimental impact on mortality due to ischemic heart disease that is greater in women than in men [13]
Summary
Gender influences the cardiac response to prolonged increases in workload, with differences at structural, functional, and molecular levels. Despite having a beneficial effect on cardiac remodelling due to hemodynamic overload, female sex is associated with greater rates of heart failure in the presence of symptomatic coronary artery disease [7,8] This finding is consistent with clinical data indicating that, of lower incidence in women, coronary artery disease is problematic once present. The presence of left ventricular hypertrophy has been shown to have a detrimental impact on mortality due to ischemic heart disease that is greater in women than in men [13] Taken together, these data indicate that female sex influences remodelling due to hemodynamic overload as well as outcome after ischemia. They suggest that the functional significance of simultaneously occurring cardiac hypertrophy and coronary artery disease differs between women than in men
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