Intrauterine exposure to chronic hypoxia in the rat leads to progressive diastolic function and increased aortic stiffness from early postnatal developmental stages.

Aim: We sought to explore whether fetal hypoxia exposure, an insult of placental insufficiency, is associated with left ventricular dysfunction and increased aortic stiffness at early postnatal ages.
Methods: Pregnant Sprague Dawley rats were exposed to hypoxic conditions (11.5% FiO ₂ ) from embryonic day E15-21 or normoxic conditions (controls). After delivery, left ventricular function and aortic pulse wave velocity (measure of aortic stiffness) were assessed longitudinally by echocardiography from day 1 through week 8. A mixed ANOVA with repeated measures was performed to compare findings between groups across time. Myocardial hematoxylin and eosin and picro-sirius staining were performed to evaluate myocyte nuclear shape and collagen fiber characteristics, respectively.
Results: Systolic function parameters transiently increased following hypoxia exposure primarily at week 2 (p < .008). In contrast, diastolic dysfunction progressed following fetal hypoxia exposure beginning weeks 1-2 with lower early inflow Doppler velocities, and less of an increase in early to late inflow velocity ratios and annular and septal E'/A' tissue velocities compared to controls (p < .008). As further evidence of altered diastolic function, isovolumetric relaxation time was significantly shorter relative to the cardiac cycle following hypoxia exposure from week 1 onward (p < .008). Aortic stiffness was greater following hypoxia from day 1 through week 8 (p < .008, except week 4). Hypoxia exposure was also associated with altered nuclear shape at week 2 and increased collagen fiber thickness at week 4.
Conclusion: Chronic fetal hypoxia is associated with progressive LV diastolic dysfunction, which corresponds with changes in nuclear shape and collagen fiber thickness, and increased aortic stiffness from early postnatal stages.
(© 2020 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society.)