Elucidation of the mechanisms of placental dysfunction after bypass and the negative effects of fetal stress (Fig 9) has allowed these issues to be addressed effectively using indomethacin and appropriate fetal anesthesia. The effective management of these two major problems has made a dramatic difference in the ability of fetal animals to survive surgical intervention and extracorporeal circulation. Characterization of various aspects of placental vascular hemodynamics using the isolated placental preparation also has added new insights into the behavior of the placental vasculature during extracorporeal circulation. These insights have been and will continue to be extremely useful in designing the ideal method of fetal extracorporeal circulatory support. In spite of these advances, further work remains before clinical application of these techniques can be applied reliably. Ideally, a specific blocker of the mediators of the placental response to cardiac bypass should be available before clinical studies are undertaken. Indomethacin, although quite effective, may have secondary effects on other vascular beds that would be potentially detrimental. Also, although the fetal stress response can be blocked adequately using fetal total spinal anesthesia, with a dramatic improvement in cardiovascular stability, this technique of anesthesia not only would be cumbersome, but also would be potentially dangerous in the human fetus. High-dose narcotic anesthesia has been shown to be very effective in neonates and infants undergoing cardiac procedures, with respect to both blockage of the stress response and maintenance of cardiac function. This technique also may be applicable in the human fetus as an effective method of blocking the stress response without causing myocardial depression or affecting peripheral vascular resistances. Unfortunately, sheep do not possess opiate receptors and, therefore, are not an appropriate model for testing narcotic anesthesia in the fetus. Future studies in the primate model using high-dose narcotic anesthesia could provide important information regarding this problem. Also, the ideal circuitry for fetal extracorporeal support has not been determined with certainty. Although a simplified circuit without an oxygenator is possible if the placenta is used as the oxygenator, this method has the disadvantages of high flow rates and placental stimulation. Extracorporeal circulation with the inclusion of an artificial oxygenator requires a somewhat more complex circuit; however, more manageable flow rates and less stimulation of placental vasculature are possible with this technique (Fig 10). All forms of fetal intervention for cardiovascular disease require an extensive understanding of the fetal pathophysiologic responses to intervention, whether the intervention involves open techniques that necessitate extracorporeal circulatory support or closed interventional techniques.(ABSTRACT TRUNCATED AT 400 WORDS)