The overall purpose of these experiments is to explore the mechanisms by which the fetal cardiovascular system adapts to long-term hypoxemia. Specifically, we plan to explore changes in fetal cardiac function during hypoxemia. We have previously shown fetal right ventricular output and function to decrease on day 3 of hypoxemia, but then to return to normal by 2 weeks and possibly to even rise above normal with continued hypoxemia. Because timing and duration of hypoxic exposure are probably crucial, we will examine sheep exposed to hypoxemia for 2-3 weeks in the last third of gestation as well as those exposed from day 30 of gestation onward. Change in cardiac performance could result from alterations in delivery, transfer, and utilization of O2 by the myocardial cell, alterations in myocardial cel energy production, and/or changes in the contactile mechanism of the cells. Therefore, we plan to examine 1) changes in coronary blood vessel reactivit that might affect O2 delivery, 2) changes in number and geometry of myocardial capillaries and mitochondria that might affect O2 transfer, 3) changes in myocardial cell oxygen consumption and metabolic enzyme levels that might affect O2 utilization and energy production, and 4) changes in contractile machinery and ability utilizing isolated papillary muscle. Thus, results will contribute to an overall understanding of fetal cardiovascular control and O2 delivery during extended periods of hypoxemia These studies are of clinical importance relative to fetus of women who reside at high altitude, those who engage in strenuous physical activity, those who are malnourished, and those who smoke.
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