Role of potassium and calcium channels in sevoflurane-mediated vasodilation in the foeto-placental circulation.

BACKGROUND: Sevoflurane has been demonstrated to vasodilate the foeto-placental vasculature. We aimed to determine the contribution of modulation of potassium and calcium channel function to the vasodilatory effect of sevoflurane in isolated human chorionic plate arterial rings. METHODS: Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 and 2 examined the role of the K+ channel in sevoflurane-mediated vasodilation. Separate experiments examined whether tetraethylammonium, which blocks large conductance calcium activated K+ (KCa++) channels (Series 1A+B) or glibenclamide, which blocks the ATP sensitive K+ (KATP) channel (Series 2), modulated sevoflurane-mediated vasodilation. Series 3 - 5 examined the role of the Ca++ channel in sevoflurane induced vasodilation. Separate experiments examined whether verapamil, which blocks the sarcolemmal voltage-operated Ca++ channel (Series 3), SK&F 96365 an inhibitor of sarcolemmal voltage-independent Ca++ channels (Series 4A+B), or ryanodine an inhibitor of the sarcoplasmic reticulum Ca++ channel (Series 5A+B), modulated sevoflurane-mediated vasodilation. RESULTS: Sevoflurane produced dose dependent vasodilatation of chorionic plate arterial rings in all studies. Prior blockade of the KCa++ and KATP channels augmented the vasodilator effects of sevoflurane. Furthermore, exposure of rings to sevoflurane in advance of TEA occluded the effects of TEA. Taken together, these findings suggest that sevoflurane blocks K+ channels. Blockade of the voltage-operated Ca++channels inhibited the vasodilator effects of sevoflurane. In contrast, blockade of the voltage-independent and sarcoplasmic reticulum Ca++channels did not alter sevoflurane vasodilation. CONCLUSION: Sevoflurane appears to block chorionic arterial KCa++ and KATP channels. Sevoflurane also blocks voltage-operated calcium channels, and exerts a net vasodilatory effect in the in vitro foeto-placental circulation.

Sevoflurane and the feto-placental vasculature: the role of nitric oxide and vasoactive eicosanoids.

BACKGROUND: The effects and mechanisms of action of volatile anesthetics on the feto-placental vasculature are not known. We aimed to quantify the vasoactive effects of sevoflurane and determine the role of nitric oxide (NO) and of vasoactive eicosanoids in mediating these effects in isolated human chorionic plate arterial rings. METHODS: Quadruplicate ex vivo human chorionic plate arterial rings were used in all studies. Series 1 quantified the vasodilation produced by sevoflurane in rings preconstricted with the thromboxane analog U46619. Series 2A-C examined the role of NO in sevoflurane-mediated vasodilation. In separate experiments, we examined the potential for the nonspecific NO inhibitors, L-NAME, L-nMMA, and the inactive D-NAME, to modulate the vasodilation produced by sevoflurane. Series 2D determined whether sevoflurane altered vascular smooth muscle sensitivity to exogenous NO. Series 3A-D examined the role of vasoactive eicosanoids in sevoflurane-mediated vasodilation. In separate experimental series, we examined whether the nonspecific cyclooxygenase inhibitor, indomethacin, or the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid, modulated sevoflurane-mediated vasodilation. RESULTS: Sevoflurane produced dose-dependent vasodilation of preconstricted chorionic plate arterial rings, with mean ring vasodilation increasing from 15 +/- 7% at 2% sevoflurane to 67 +/- 17% (mean +/- sd) at 8% sevoflurane. Blockade of NO synthase did not attenuate the vasodilator effects of sevoflurane. Sevoflurane did not alter smooth muscle sensitivity to NO. Indomethacin augmented sevoflurane vasodilation at 10(-5) M, but not at 10(-6) M. Conversely, nordihydroguaiaretic acid attenuated sevoflurane-mediated vasodilation at 3 x 10(-6) M but not at 3 x 10(-7) M. CONCLUSIONS: Sevoflurane was a vasodilator in the feto-placental vasculature in this in vitro model. Sevoflurane-mediated vasodilation is NO and cyclooxygenase-independent and appears to be mediated in part via a lipoxygenase generated vasodilator eicosanoid.

Maternal brain death and somatic support.

Brain death is a concept used in situations in which life-support equipment obscures the conventional cardiopulmonary criteria of death, and it is legally recognized in most countries worldwide. Brain death during pregnancy is an occasional and tragic occurrence. The mother and fetus are two distinct organisms, and the death of the mother mandates consideration of the well-being of the fetus. Where maternal brain death occurs after the onset of fetal viability, the benefits of prolonging the pregnancy to allow further fetal maturation must be weighed against the risks of continued time in utero, and preparations must be made to facilitate urgent cesarean section and fetal resuscitation at short notice. Where the fetus is nonviable, one must consider whether continuation of maternal organ supportive measures in an attempt to attain fetal viability is appropriate, or whether it constitutes futile care. Although the gestational age of the fetus is central to resolving this issue, there is no clear upper physiological limit to the prolongation of somatic function after brain death. Furthermore, medical experience regarding prolonged somatic support is limited and can be considered experimental therapy. This article explores these issues by considering the concept of brain death and how it relates to somatic death. The current limits of fetal viability are then discussed. The complex ethical issues and the important variations in the legal context worldwide are considered. Finally, the likelihood of successfully sustaining maternal somatic function for prolonged periods and the medical and obstetric issues that are likely to arise are examined.

Recent advances in obstetric anesthesia.

The low-dose technique of combined spinal/epidural analgesia is to be welcomed in obstetrics. Its merits include rapid onset of analgesia, with the flexibility of an epidural technique, and high maternal satisfaction. It is a safe and effective technique. Pulse oximetry should be employed when using intrathecal opioids. Commercially available combined-needle devices may make this technique more attractive to users. The role of spinal anesthesia for emergency cesarean section in severe preeclampsia has been reevaluated recently. We consider it a feasible option for those severely preeclamptic women requiring urgent cesarean section who do not have an epidural catheter in place. The choice of anesthetic technique for this patient population should be made on clinical judgment and not on anticipated hemodynamic changes. Spinal anaesthesia for cesarean section is associated with hypotension; however, certain interventions may reduce the incidence and severity of the hypotension. An increase in cardiac output appears to be key in attenuating the hypotensive response to spinal anesthesia. Colloids have exhibited most success in this regard. At our institution, we do not delay spinal anesthesia for urgent cesarean section in order to administer a predetermined volume of fluid; in such cases, we simultaneously administer a fluid preload and spinal anesthesia. Recent studies regarding the use of cell savers for blood conservation in obstetrics are based on small numbers of patients. These studies show great promise, particularly with the modern emphasis on avoiding blood transfusion, which can be massive in this usually young patient population.