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 concentrations of lidocaine loses its cardiovascular adaptations to asphyxia, 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 present study was to determine whether the adverse effects of lidocaine noted in the preterm fetal lamb also occur with bupivacaine and whether the inhibition of NO results in effects similar to those of bupivacaine. Thirty-two chronically prepared pregnant sheep were studied at 117-119 days' gestation. Maternal and fetal blood pressure, heart rate, and acid-base state were evaluated. Fetal organ blood flows were determined using 15-microM diameter dye-labeled microspheres. After a control period, mild to moderate asphyxia (fetal PaO2 15 mm Hg) was induced by partial umbilical cord occlusion and maintained throughout the experiment. Ewes in Group I (n = 13) were given a two-step intravenous infusion of bupivacaine for 180 min. Fetuses in Group II (n = 12) received 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 increases noted in L-NAME-treated fetuses. At 90 min of stable asphyxia, there was a significant decrease in fetal PaO2 and pHa and an increase in PaCO2 and mean arterial blood pressure. There was also an increase in blood flow to the adrenals, myocardium, and cerebral cortex, whereas blood flow to the placenta decreased. Administration of bupivacaine during asphyxia did not affect the changes in mean arterial blood pressure and acid-base state but did abolish the increases in blood flows to the myocardium and cerebral cortex. Injection of L-NAME to the asphyxiated fetus resulted in an increase in mean arterial blood pressure above the level noted at 90 min of cord occlusion, and an increase in fetal PaO2 toward control levels. This was accompanied by a reduction in organ blood flows to preasphyxia levels. In asphyxiated Group III fetuses, titration of the phenylephrine infusion to achieve blood pressure increases similar to those noted with L-NAME were also associated with an increase in fetal PaO2. These data indicate that bupivacaine abolishes some of the circulatory adaptations to mild to moderate asphyxia induced by partial cord occlusion in the preterm fetal lamb. It is not clear whether these effects of bupivacaine are due to inhibition of NO.


CONCLUSIONS
In the preterm fetal lamb, clinically relevant plasma concentrations of bupivacaine achieved by intravenous infusion to the pregnant ewe (80% gestation) abolished some of the fetal cardiovascular adaptations to asphyxia induced by partial umbilical cord occlusion.
Santos
A C
AC
Department of Anesthesiology, Obstetrics and Gynecology, Albert Einstein College of Medicine/Montefiore Medical Center, Bronx, New York, USA.
Yun
E M
EM
Bobby
P D
PD
Noble
G
G
Arthur
G R
GR
Finster
M
M
D000222:Adaptation, Physiological / Q000187:drug effects*; D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001237:Asphyxia / Q000097:blood / Q000503:physiopathology*; D001794:Blood Pressure / Q000187:drug effects; D002045:Bupivacaine / Q000494:pharmacology*; D002245:Carbon Dioxide / Q000097:blood; D005260:Female; D005312:Fetal Blood / Q000737:chemistry / Q000187:drug effects; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006863:Hydrogen-Ion Concentration; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors* / Q000502:physiology; D010100:Oxygen / Q000097:blood; D010656:Phenylephrine / Q000494:pharmacology*; D011247:Pregnancy; D012039:Regional Blood Flow / Q000187:drug effects; D012756:Sheep; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
D000779:Anesthetics, Local; D014662:Vasoconstrictor Agents; D002245:Carbon Dioxide; D010656:Phenylephrine; D009569:Nitric Oxide; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester; D002045:Bupivacaine