THE EFFECTS OF BUPIVACAINE, L-NITRO-L-ARGININE-METHYL ESTER, AND PHENYLEPHRINE ON CARDIOVASCULAR ADAPTATIONS TO ASPHYXIA IN THE PRETERM FETAL LAMB

The preterm fetal lamb that is exposed to clinically relevant plasma c oncentrations of lidocaine loses its cardiovascular adaptations to asp hyxia, and its condition deteriorates further. Nitric oxide (NO) is an important regulator of vascular tone, and local anesthetics are known to inhibit endothelium-dependent vasodilation. The purpose of the pre sent study was to determine whether the adverse effects of lidocaine n oted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacai ne. Thirty-two chronically prepared pregnant sheep were studied at 117 -119 days' gestation. Maternal and fetal blood pressure, heart rate, a nd Fetal acid-base state were evaluated. Fetal organ blood flows were determined using 15-mu M diameter dye-labeled microspheres. After a co ntrol period, mild to moderate asphyxia (fetal Pao(2) 15 mm Hg) was in duced by partial umbilical cord occlusion and maintained throughout th e experiment. Ewes in Group I (n = 13) were given a two-step intraveno us infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) r eceived an intravenous injection of L-nitro-L-arginine-methyl ester (L -NAME) (25 mg/kg) and measurements were taken 10 and 30 min after the injection. A third group (Group III) of fetuses (n = 7) were given an intravenous infusion of phenylephrine to mimic the blood pressure incr eases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, t here was a significant decrease in fetal Pao(2) and pHa and an increas e in Paco(2) and mean arterial blood pressure. There was also an incre ase in blood flow to the adrenals, myocardium, and cerebral cortex, wh ereas blood flow to the placenta decreased. Administration of bupivaca ine during asphyxia did not affect the changes in mean arterial, blood pressure and acid-base state but did abolish the increases in blood f lows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in mean arterial blood pres sure above the level noted at 90 min of cord occlusion, and an increas e in fetal Pao(2) toward control levels. This was accompanied by a red uction in organ blood flows to preasphyxia levels. In asphyxiated Grou p III fetuses, titration of the phenylephrine infusion to achieve bloo d pressure increases similar to those noted with L-NAME were also asso ciated with an increase in fetal Pao(2). These data indicate that bupi vacaine abolishes some of the circulatory adaptations to mild to moder ate asphyxia induced by partial cord occlusion in the preterm fetal la mb. It is clear whether these effects of bupivacaine are due to inhibi tion of NO. Implications: In the preterm fetal lamb, clinically releva nt plasma concentrations of bupivacaine achieved by intravenous infusi on to the pregnant ewe (80% gestation) abolished some of the fetal car diovascular adaptations to asphyxia induced by partial umbilical cord occlusion.