Unveiling gender differences in demand ischemia: a study in a rat model of genetic hypertension

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Objective: Female gender is associated with reduced tolerance against acute ischemic events and a higher degree of left ventricular hypertrophy under chronic pressure overload. We tested whether female and male rats with left ventricular hypertrophy present the same susceptibility to demand ischemia. Methods: Hearts from hypertrophied female and male salt-resistant and salt-sensitive Dahl rats (n = 8 per group) underwent 30 min of demand ischemia induced by rapid pacing (7 Hz) and an 85% reduction of basal coronary blood flow, followed by 30 min of reperfusion on an isovolumic red cell perfused Langendorff model. Results: In female hearts, high-salt diet induced a pronounced hypertrophy of the septum (2.38 ± 0.09 vs 2.17 ± 0.08 mm; p < 0.01), whereas male hearts showed the greatest increase in the anterior/posterior wall of the left ventricle (LV) (3.19 ± 0.22 vs 2.01 ± 0.16 mm; p < 0.05) compared with salt-resistant controls. At baseline, LV-developed pressure/g LV was significantly higher in female than male hearts (200 ± 13 and 196 ± 14 vs 161 ± 10 and 152 ± 15 mmHg g-1; p < 0.01), independent of hypertrophy, indicating greater contractility in females. During ischemia, LV-developed pressure decreased in all groups; at the end of reperfusion, hypertrophied female and male hearts showed higher developed pressures independent of gender (148 ± 3 and 130 ± 8 vs 100 ± 7 and 85 ± 6 mmHg; p < 0.01). In contrast, diastolic pressure was more pronounced in female than in male hypertrophied hearts during ischemia and reperfusion (24 ± 3 vs 12 ± 2 mmHg; p < 0.01). Conlusions: In the pressure overload model of the Dahl salt-sensitive rat, female gender is associated with a more pronounced concentric hypertrophy, whereas male hearts develop a more eccentric type of remodeling. Although present at baseline, after ischemia/reperfusion systolic function is gender-independent but more determined by hypertrophy. In contrast, diastolic function is gender-dependent and aggravated by hypertrophy, leading to pronounced diastolic dysfunction. We can conclude that in the malignant setting of demand ischemia/reperfusion gender differences in hypertrophied hearts are unmasked: female hypertrophied hearts are more susceptible to ischemia/reperfusion than males. To determine whether in female hypertensive patients with acute coronary syndromes, diastolic dysfunction could contribute to the worse clinical course, further experimental and clinical studies are needed. © 2007 European Association for Cardio-Thoracic Surgery.




Podesser, B. K., Jain, M., Ngoy, S., Apstein, C. S., & Eberli, F. R. (2007). Unveiling gender differences in demand ischemia: a study in a rat model of genetic hypertension. European Journal of Cardio-Thoracic Surgery, 31(2), 298–304. https://doi.org/10.1016/j.ejcts.2006.10.041

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