Surface arteries and arterioles of the brain are primary regulators of cerebrovascular resistance to blood flow. They may also function to regulate pressure of intracerebral microvessels. These processes are of utmost importance during development and specific studies on fetal cerebral arteries in-vivo will lead to further in depth understanding of the mechanisms. Only the closed cranial window technique allows for direct observation and experimental manipulation of cerebral arterioles in-vivo. These studies investigate specific metabolic factors in the regulation of the cerebral vascular resistance of the fetus during normoxic and hypoxic states. Physiological evidence suggests that accumulation of adenosine in extracellular and perivascular spaces of brain tissue plays a major role in the regulation of vascular resistance during conditions of inadequate oxygen supply. This proposal will attempt to evaluate the role of adenosine in the regulation of local vascular tone in the premature fetal lamb under conditions of normoxic and hypoxic states. Specifically, cerebral arteries will be studied in-vivo regarding their responsivity to adenosine, hypoxia, and other vasodilatory stimuli, CO2 and acetylcholine. Experiments are designed to inhibit or enhance adenosine regulatory processes and evaluate the effects of hypoxic vasodilation. Additional experiments investigate the specific enzymatic function of immature fetal brain tissue relating to adenosine metabolism, and its formation during hypoxia. Analysis of cerebrovascular responses to hypoxia following administration of compounds that impair adenosine formation, function, or degradation, will yield information assessing the importance of adenosine as the mediator of hypoxic vasodilation. The results of this research will contribute to understanding the regulation of cerebral circulation and tissue oxygenation in the fetus in-utero and elucidate maturational aspects of vascular control mechanisms.
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