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

Objective: Female gender is associated with reduced toterance against acute ischemic events and a higher degree of left ventricular hypertrophy under chronic pressure overload. We tested whether female and mate rats with left ventricular hypertrophy present the same susceptibility to demand ischemia. Methods: Hearts from hypertrophied female and mate 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 mate hearts showed the greatest increase in the anterior/ posterior watt 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 mate 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-devetoped pressure decreased in all groups; at the end of reperfusion, hypertrophied female and mate 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 mate hypertrophied hearts during ischemia and reperfusion (24 +/- 3 vs 12 +/- 2 mmHg; p < 0.01). Contusions: In the pressure overload model of the Dahl satt-sensitive rat, female gender is associated with a more pronounced concentric hypertrophy, whereas mate 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 mates. 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. (c) 2007 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.