Cocaine in pregnancy: the effect of maternal administration of cocaine on the maternal and fetal pituitary-adrenal axes.

The effects of cocaine on the maternal and fetal pituitary-adrenal axis in vivo during pregnancy have not been reported. Six pregnant ewes and their fetuses underwent instrumentation at 113 to 119 days' gestation. Ewes were assigned to receive an intravenous bolus injection of vehicle or cocaine (0.5, 1.0, or 2.0 mg.kg-1) at 124 to 136 days' gestation. Maternal arterial blood gases, fetal pH and fetal PCO2 were unchanged after injection of cocaine or vehicle. After administration of 2.0 mg.kg-1 cocaine, arterial fetal PO2 fell 3.2 +/- 1.72 mm Hg (p less than 0.05) at +5 minutes, returning to baseline by +15 minutes. Maternal and fetal adrenocorticotropin levels rose within 5 minutes after the highest cocaine dose (p less than 0.05). There was a significant (p less than 0.05) increase in maternal cortisol at all doses of cocaine and in fetal cortisol at +15 minutes after the 2.0 mg.kg-1.     

Intravenous infusion of magnesium sulfate and regional redistribution of fetal blood flow during maternal hemorrhage in late-gestation gravid ewes

OBJECTIVES: Even though magnesium sulfate is commonly prescribed for women with preeclampsia as prophylaxis against seizure and for women with preterm labor as a tocolytic agent there is limited information about its effects on the fetus. It is of particular concern that women with preeclampsia or in premature labor are at high risk for abruptio placentae with consequent compromise of fetal oxygenation. Magnesium sulfate is a vasodilator and thus may exert cardiovascular effects on the fetus. The goal of this study was to evaluate the effects of magnesium sulfate on fetal organ blood flow, especially regional cerebral blood flow, during the stressful condition of maternal hemorrhage. STUDY DESIGN: Studies were performed with 11 long-term instrumented pregnant ewes and their fetuses at 121 to 128 days' gestation (term, 147 days' gestation). Animals were randomly allocated to either the experimental (n = 5) or the control (n = 6) group. After a 60-minute baseline period, experimental fetuses received intravenous magnesium sulfate diluted in 0.9% sodium chloride (0.3 g loading dose, then 0.3 g/h at a rate of 3 mL/h) and control fetuses were infused with an equivalent volume of intravenous 0.9% sodium chloride. After 60 minutes of this infusion-only period, the infusions were continued and ewes were intermittently bled 4 times at a rate of 5 mL/kg for 10 minutes with 5 minutes between hemorrhages. The total blood lost at the end of the hemorrhage-plus-infusion hour was 20 mL/kg. The infusions were continued and the sheep were observed for 1 hour after this period (posthemorrhage period). At the end of baseline, infusion-only, and hemorrhage-plus-infusion periods, fetal and maternal blood pressures and blood gas values were measured and fetal organ blood flows were determined through a fluorescent microsphere technique. Repeated-measures analysis of variance and Wilcoxon tests were used to determine the significance of changes in hemodynamic, blood gas, and organ blood flow parameters between different time points within each group. Comparisons between groups were made with rank sum tests (Mann-Whitney tests). RESULTS: There were no significant differences between groups or within groups for baseline and infusion-only measurements in any measured hemodynamic or hematologic factor. Mean maternal blood pressure decreased significantly (P <.05) after hemorrhage, with similar median decrements in both control and experimental groups of 41 mm Hg (interquartile range, 24-57 mm Hg) and 41 mm Hg (interquartile range, 12-43 mm Hg), respectively. There were no significant differences between groups in fetal blood gas values or hemodynamic parameters. Fetal arterial PO(2) decreased significantly after hemorrhage plus infusion, with similar mean (+/-SEM) decreases in control and experimental groups of 5.9 +/- 1.4 mm Hg and 4.5 +/- 1.5 mm Hg, respectively. Fetal pH also decreased significantly in both groups. After hemorrhage plus infusion there were significant increases in fetal regional cerebral and myocardial blood flows in both groups. Adrenal blood flow increased significantly from baseline (214%, 183%-294%) in the control group after hemorrhage plus infusion but not in the experimental group. No other difference in organ blood flow between control and experimental groups was observed. Significant regional variations in cerebral blood flow were not observed in either group at any time. CONCLUSIONS: In these initially healthy, late-gestation fetal lambs magnesium sulfate exposure did not impair cardiac output redistribution, nor did it cause fetal death in response to maternal hemorrhage.     

Amniotic fluid volume responses to amnio-infusion of amniotic fluid versus lactated Ringer's solution in fetal sheep

OBJECTIVE: The present study tested the hypothesis that an intra-amniotic infusion of amniotic fluid (AF) would produce a more sustained increase in AF volume than an infusion of lactated Ringer's solution. METHODS: Five chronically catheterized, late-gestation fetal sheep were studied over two 5-day periods with AF volume measured daily. After baseline measurements on day 1, 1 L of either warmed, previously frozen AF or warmed lactated Ringer's solution was infused intra-amniotically over 60 minutes. Two days later, the other fluid was infused. During the second week, fluids were infused in the opposite order. Analysis of variance (ANOVA) was used for statistical testing. RESULTS: Following intra-amniotic infusion (n = 20) of 1007 +/- 7 (SE) mL of either AF or Ringer's solution, intra-amniotic retention of the infused fluid was only moderate after 1 day (37.2% +/- 7.9%, P <.001) and was not significantly different from zero after 2 days (16.5% +/- 9.5%, P =.1). There were no significant differences in AF volume following infusion of AF versus lactated Ringer's solution or the order in which they were infused. AF compositional changes were similar except that pH and bicarbonate concentration were reduced as expected immediately after lactated Ringer's solution with a return to normal values after 1 day. AF lactate increased after lactated Ringer's solution infusion, declining to baseline values after 2 days. Fetal urine flow rate increased by 75% +/- 24% at 1 day postinfusion and there was no difference between infusates. CONCLUSIONS: The expansion of AF volume over 2 days following amnio-infusion does not appear to depend on minor compositional differences or the presence of microconstituents such as hormones, cytokines, or growth factors that are normally present in AF.     

Does the intravenous infusion of ritodrine or magnesium sulfate alter the hemodynamic response to hemorrhage in gravid ewes?

The purpose of this study was to determine whether the intravenous infusion of ritodrine or magnesium sulfate alters the hemodynamic response to maternal hemorrhage in gravid ewes. Twenty-seven experiments were performed in 12 chronically instrumented animals at 0.8 of timed gestation. Each animal was subjected to hemorrhage (20 ml/kg over 60 minutes) during infusion of ritodrine (0.004 mg/kg/min), magnesium sulfate (4 gm/hour), or saline solution control. Infusion of magnesium sulfate increased the mean (+/- SEM) maternal serum magnesium concentration to 4.8 +/- 0.2 mg/dl before hemorrhage and 5.3 +/- 0.3 mg/dl after hemorrhage. At the end of hemorrhage maternal mean arterial pressures were 63% +/- 4%, 82% +/- 2%, and 79% +/- 6% of baseline in the magnesium sulfate, ritodrine, and control groups, respectively. The maternal mean arterial pressure response in the magnesium sulfate group differed significantly from the maternal mean arterial pressure responses in the ritodrine and control groups (p less than 0.01). Fetal pH was decreased significantly only in the magnesium sulfate group (p = 0.0001). Fetal PO2 was decreased significantly in the magnesium sulfate and ritodrine groups (p less than 0.001) but not in the control group. We conclude that magnesium sulfate but not ritodrine, worsened the maternal hypotensive response to hemorrhage in gravid ewes.     

Transplacental, amniotic, urinary, and fetal fluid dynamics during very-large-volume fetal intravenous infusions

With rapid intravenous infusion of very large volumes of isotonic saline solutions into the fetus, the fluid could stay within the fetal body, thereby creating hydrops fetalis, be transferred into the amniotic fluid through the fetal kidneys, thereby creating polyhydramnios, or be transferred across the placenta into the maternal circulation. This study was designed to explore these possibilities. After a 1-hour control period, 10 near-term chronically catheterized ovine fetuses were infused intravenously with 4 L (greater than 100% of fetal weight) of either isotonic saline solution or lactated Ringer's solution over 4 hours. Fetal arterial pressure was significantly elevated by 7 mm Hg throughout the infusion (p less than 0.00001). Venous pressure underwent a transient rise (4.8 mm Hg) at 20 minutes of infusion and remained elevated (2.7 mm Hg) during the rest of the infusion (p less than 0.00001). Fetal urine flow increased by an average of 5.7 +/- 0.4 ml/min throughout the infusion (p less than 0.00001) and accounted for 34.1% +/- 2.6% of the infused volume. Estimated fetal extracellular fluid volume increased by 17.7% +/- 1.8% of the infused volume. Because fetal fluid retention, urine flow, and amniotic fluid volume changes accounted for only half of the infused fluid, the remainder of the infused volume must have crossed the placenta and entered the maternal circulation. Given the above changes in vascular pressures, this requires a filtration coefficient of the placenta 50 to 100 times the previously reported values. Thus we conclude that relatively small changes in fetal vascular pressures dramatically alter the filtration capacity of the ovine placenta and transplacental volume flow.     

Tampon-induced changes in vaginal oxygen and carbon dioxide tensions

Vaginal oxygen and carbon dioxide tensions were measured continuously in a group of normal young women on the second day of menstruation during a 90-minute period. PO2 averaged 3 mm Hg (+/- 11 SD) and PCO2 averaged 64 mm Hg (+/- 13 SD). The value rose to that of atmospheric air when a tampon was inserted and gradually fell, giving a mean value of 112 mm Hg (+/- 18 SD) during the following 90 minutes; preinsertion values were reached in about 8 hours. Carbon dioxide rose rapidly to almost preinsertion values (mean value of 50 mm Hg +/- 12 SD) during the 90-minute period and remained steady at this level during extended periods. As in vitro studies have indicated an oxygen-dependent production of a toxin-like protein from Staphylococcus aureus, it is suggested that intravaginal tampons may be a risk factor in the development of toxic shock syndrome by supplying oxygen, thus changing the vaginal microenvironment from anaerobic to aerobic.     

Pregnancy increases cardiovascular toxicity to cocaine

The effects of intravenous cocaine on heart rate and blood pressure were studied in pregnant and oophorectomized nonpregnant ewes. In response to intravenous cocaine doses of 1.0 and 2.0 mg/kg, both pregnant and nonpregnant ewes demonstrated dose-dependent increases in systolic, diastolic, mean arterial, and pulse pressures with return to baseline by 30 to 60 minutes after cocaine administration. However, at both doses (1.0 and 2.0 mg/kg) pregnant ewes demonstrated greater increases in mean arterial pressure (+29.6%, +48.7%) than nonpregnant ewes (+15.6%, +27.7%) during the first 5 minutes after cocaine administration. Thereafter the responses were similar. Thus pregnancy increases the cardiovascular toxicity to cocaine.     

A unique hypertonic response to hypotonic infusion in the pregnant ewe.

OBJECTIVE: The purpose of this study was to compare the responses of the maternal ewe to intravenous volume expansion with either sufficient lactated Ringer's solution to elevate maternal venous pressure or sufficient hypotonic fluid to reduce blood osmolality. STUDY DESIGN: Chronically catheterized pregnant sheep were intravenously infused over 4 hours with either commercial lactated Ringer's solution (5.55 +/- 0.50 L/hr, 255 mOsm/kg, mildly hypotonic) or diluted Ringer's solution (2.04 +/- 0.27 L/hr, 150 mOsm/kg, markedly hypotonic). Data were statistically analyzed with two- and three-factor analyses of variance and bivariate regression analysis. RESULTS: During the mildly hypotonic infusion (n = 8) the maternal blood osmolality changes were -5.1 +/- 1.2, +2.7 +/- 1.0 and +6.8 +/- 1.1 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. In four of the eight animals in this group profuse diarrhea developed. During the markedly hypotonic infusion (n = 11) the maternal blood osmolality changes were -9.9 +/- 1.1, -15.9 +/- 2.5, and -10.4 +/- 2.2 mOsm/kg at 1 and 4 hours of infusion and 1 hour after the infusion. Although urine osmolalities were significantly less than the osmolality of the infusate in both groups, only during the mildly hypotonic infusion was there a net loss of free water by the kidneys. The renal free water loss, the venous pressure increase, and the blood osmolality decrease were not significantly different whether diarrhea did or did not develop. CONCLUSION: The infusion of large volumes of mildly hypotonic Ringer's solution to the pregnant ewe produces a paradoxic increase in maternal plasma osmolality as a result of the excretion of large volumes of free water by the kidneys, and if the venous pressure is increased more than about 6 mm Hg with this infusion, diarrhea develops in the animals.     

Peripartum colloid osmotic pressure changes: effects of controlled fluid management

A prospective, fluid-controlled study of serially measured colloid osmotic pressure changes in the peripartum period was undertaken. Seventeen patients with uncomplicated pregnancies undergoing elective cesarean section at term were administered a predelivery bolus of 15 ml/kg of lactated Ringer's solution prior to operation. Maintenance crystalloid fluids were infused at 125 to 150 ml/hr both intraoperatively and post partum without the addition of blood or other colloid solutions. Serial colloid osmotic pressure measurements were obtained before hydration, after hydration, after delivery, and at 6 and 24 hours post partum. The results demonstrated a 15.9% decline in colloid osmotic pressure immediately following the hydration bolus (20.7 +/- 1.5 to 17.4 +/- 1.8 mm Hg) (p less than 0.01). A further decline in colloid osmotic pressure to 16.6 +/- 1.7 mm Hg occurred after delivery and represented an overall 22% decrease from the baseline value (p less than 0.05). The lowest mean colloid osmotic pressure value occurred at 6 hours post partum (16.1 +/- 1.1 mm Hg). These data support previous observations that colloid osmotic pressure is uniformly lowered in the immediate postpartum period with peak reductions identified at 6 hours following delivery. In addition, intravenous crystalloid administration during the peripartum interval can substantially influence this decline in colloid osmotic pressure. Although no clinical evidence of cardiopulmonary compromise was observed in this set of normal gravid women, these data may be useful in the management of the parturient patient with established risk factors for pulmonary edema where alterations in the pulmonary capillary wedge pressure-colloid osmotic pressure gradient have been shown to correlate with the development of this complication.     

Fetoplacental vascular responses to prostacyclin after thromboxane-induced vasoconstriction

The vasodilator prostacyclin is produced by fetal tissues and may serve to protect umbilical blood flow. We hypothesized that prostacyclin could reverse fetoplacental vasoconstriction produced by a thromboxane mimic (U-46619). Fetal regional blood flow was measured by the radioactive microsphere technique in six unanesthetized, near-term ovine fetuses. Measurements were made in the control period, again 20 minutes after a fetal infusion of U-46619 was begun, and finally 20 minutes after prostacyclin was added to the U-46619 infusion. Mean arterial pressure rose significantly in response to U-46619 (38 +/- 1 to 51 +/- 2 mm Hg, p less than 0.01) and returned to baseline after prostacyclin (42 +/- 2 mm Hg). Renal resistance was increased from 0.16 +/- 0.01 to 0.22 +/- 0.01 mm Hg.ml-1.min.100 gm-1 (p less than 0.05) by U-46619 and decreased significantly (p less than 0.05) below baseline by addition of prostacyclin (0.10 +/- 0.02 mm Hg.ml-1.min.100 gm-1). Placental resistance also increased significantly (p less than 0.03) in response to U-46619 (from 0.15 +/- 0.01 to 0.21 +/- 0.01 mm Hg.ml-1.min.kg-1 fetal weight) but was further increased to 0.29 +/- 0.03 mm Hg.ml-1.min.kg-1 fetal weight by the addition of prostacyclin. Umbilical placental blood flow decreased significantly (p less than 0.03) when prostacyclin was added to U-46619 (315 +/- 40 to 195 +/- 30 ml.min-1.kg-1 fetal weight). Whereas U-46619 had no effect on fetal arterial blood gases, the addition of prostacyclin resulted in significant fetal acidosis (p less than 0.03). We conclude that thromboxane mimic causes fetal hypertension and renal and placental vasoconstriction. Prostacyclin reverses hypertension and renal vasoconstriction but, unexpectedly, worsens fetal placental vasoconstriction produced by thromboxane. It is likely that the observed fetal acidosis is a result of compromised placental function.     

Fetal and maternal endocrine responses to prolonged reductions in uterine blood flow in pregnant sheep

To examine the effects of sustained (48-hour) hypoxemia on fetal and maternal adrenocorticotropic hormone concentrations and on maternal progesterone, uterine blood flow was reduced in eight sheep at day 128 of pregnancy by means of an adjustable Teflon clamp placed around the maternal common internal iliac artery. Control measurements were made in four animals in which the vascular clamp was not adjusted. Fetal PaO2 fell from 20.6 +/- 1.1 mm Hg (mean +/- SEM) to 16.6 +/- 0.6 mm Hg within 1 hour after application of the clamp and remained suppressed during 48 hours. There was a transient acidemia at 1 to 2 hours that had corrected by 8 hours. Fetal adrenocorticotropic hormone levels rose from 24 +/- 6 to 1320 +/- 205 pg/ml at 2 hours but decreased by 16 hours. Measured by high-pressure liquid chromatography, more than 95% of immunoreactivity corresponded to adrenocorticotropic hormone1-39. Fetal cortisol levels rose by 6 hours and remained elevated through 48 hours. Maternal adrenocorticotropic hormone, cortisol, and progesterone levels were unchanged during the study period. We conclude that fetal hypoxemia-acidemia after restriction of uterine blood flow provokes fetal adrenocorticotropic hormone release, but the elevation in adrenocorticotropic hormone is not sustained. However, the level of fetal cortisol rises progressively, consistent with fetal adrenal activation.     

Fetal responses to maximal swimming and cycling exercise during pregnancy

Fetal responses to maximal maternal exercise were studied during cycle ergometry and tethered swimming in 13 untrained subjects at 25 and 35 weeks' gestation. The fetal heart rate (FHR) and uterine and umbilical artery waveforms were measured before exercise, immediately after exercise, and at 5-minute intervals during 20 minutes of recovery. The mean maternal maximal heart rate was 179 +/- 12 beats per minute and did not differ between swimming and cycling exercise trials. Six episodes of transient bradycardia occurred after a total of 45 maximal exercise trials. The mean FHR decreased slightly immediately after exercise, then increased approximately ten beats above baseline levels at 10-20 minutes after exercise (P less than .02). The changes from baseline in FHR were greater after cycling than after swimming. Changes observed in the systolic-diastolic ratio (S/D) of the umbilical artery could be accounted for by the FHR variations. The S/D of the uterine artery was significantly higher after cycling than after swimming (P = .05). We conclude that maximal maternal exercise during pregnancy causes transient fetal bradycardia in approximately 15% of cases, in cycling more often than in swimming.     

Hemodynamic effects of intravenous cocaine on the pregnant ewe and fetus

Cocaine is a potent vasoconstrictive agent that is currently the subject of widespread drug abuse. Because little is known of the physiologic responses to cocaine in pregnancy, the effects of intravenous cocaine on uterine blood flow and other maternal and fetal cardiovascular parameters were studied. Eight ewes in late pregnancy were equipped with electromagnetic flow probes around both uterine arteries and catheters were placed in the maternal and fetal inferior vena cavae and aortas. Bolus intravenous infusion of 0.5 and 1.0 mg/kg of maternal body weight achieved peak plasma cocaine levels similar to those observed in human subjects after abuse of the drug (mean level = 229 to 400 ng/ml, n = 8). After bolus infusion of 0.5 or 1.0 mg/kg of cocaine, mean maternal arterial pressure increased 32% and 37%, respectively (p less than 0.005). Fetal blood pressure rose 12.6% after a dosage of 0.5 mg/kg of cocaine. These cocaine infusions significantly decreased uterine blood flow by 36% and 42% for a duration of 15 minutes (p less than 0.005). Analysis of maternal catecholamine responses demonstrated a significant (210%) rise in plasma norepinephrine levels after cocaine infusion. These studies demonstrate that cocaine, when administered in doses that produce plasma levels observed in humans, significantly decreases uterine blood flow for a duration of greater than or equal to 15 minutes while inducing a hypertensive response in the pregnant ewe and fetus.     

Effect of maternal cocaine administration on maternal and fetal glucose, lactate, and insulin in sheep

Although cocaine use during pregnancy is an important cause of perinatal morbidity and mortality, there are no reports of its effect on maternal and fetal carbohydrate metabolism. Six pregnant ewes and their fetuses were instrumented under halothane general anesthesia at 113-119 days' gestation. Between 124-135 days' gestation, the ewes received a single infusion of vehicle or cocaine (1.0 or 2.0 mg/kg) into the jugular vein. At least 24 hours was allowed between successive injections. Maternal and fetal blood samples were drawn at 30 and 20 minutes before and at 5, 15, 30, and 60 minutes after the injection. Both maternal and fetal glucose and lactate concentrations increased (P less than .05) after injection of cocaine at 2.0 mg/kg. There were no significant changes in maternal or fetal plasma insulin concentrations after vehicle or cocaine administration. Induction of hyperglycemia and lactacidemia could be mechanisms whereby cocaine exerts its adverse effects during pregnancy.     

Effect of prolonged asphyxia on skin blood flow in fetal lambs

Objective: To determine the effect of a prolonged period of asphyxia on skin blood flow, a potential indicator of fetal cardiovascular responses to asphyxia, in the chronically catheterized fetal lamb. Methods: Eight chronically instrumented pregnant ewes were studied at 118 +/- 1 days' gestation. After a control period, fetal acid-base status was assessed and regional blood flows were determined with dye-labeled microspheres. Fetal asphyxia was then induced by partial umbilical cord occlusion, decreasing fetal arterial oxygen pressure to 15 torr while maintaining pH above 7.28. Fetal cardiovascular status was monitored continuously. Fetal acid base status was evaluated every 10-15 minutes during cord occlusion. Regional blood flow determinations were repeated after 90 minutes of stable asphyxia. Results are expressed as the mean +/- standard error. Student t test for paired data was used to compare hemodynamic, acid-base, and regional blood flow determinations before cord occlusion and after 90 minutes of asphyxia.Results: There was a significant increase in blood flow to the fetal scalp from a control value of 52 +/- 8 mL per minutes per 100 g to 175 +/- 30 mL per minute per 100 g at 90 minutes of asphyxia (P =.01). Similarly, there was an increase in blood flow to the skin overlying the fetal hindquarter from 39 +/- 12 mL per minute per 100 g during control to 153 +/- 47 mL per minute per 100 g at asphyxia (P =.038). Conclusion: In the chronically instrumented fetal lamb, a 90-minute period of asphyxia produced by partial cord occlusion resulted in a significant increase in blood flow to the fetal skin.     

Effects of dexamethasone on the uterine and umbilical vascular beds during basal and hypoxemic conditions in sheep

OBJECTIVE: The purpose of the study was to test the hypotheses that maternal treatment with dexamethasone leads to a reduction in basal umbilical blood flow and diminishes the fetal umbilical hemodynamic response to acute hypoxemic stress in sheep. STUDY DESIGN: While under general anesthesia, 23 ewes and their fetuses were instrumented with vascular catheters and transonic blood flow probes around a uterine and umbilical artery at 117 days of gestation (term, approximately 145 days). At 124 days, the ewes were injected intramuscularly with 2 doses of either dexamethasone (12 mg) or saline solution at 24-hour intervals. All animals experienced 2 episodes of hypoxemia during treatment (125+/-1 days) and after treatment (128+/-1 days). RESULTS: Maternal dexamethasone treatment caused a sustained increase in fetal arterial blood pressure (from 41+/-3 mm Hg to 45+/-3 mm Hg) and a transient fall in umbilical vascular conductance (from 6.2+/-0.9 mL. min(-1). [mm Hg](-1) to 5.4+/-0.7 mL. min(-1). [mm Hg](-1)). During both episodes of hypoxemia, there was a significant increase in umbilical blood flow in the controls, but not in the dexamethasone-treated animals. CONCLUSION: Maternal dexamethasone treatment with doses used in human clinical practice significantly decreased basal umbilical vascular conductance and prevented the normal increase in umbilical blood flow that is induced by acute hypoxemia in fetal sheep.     

Protection of liver ischemia due to inflow occlusion using prior perfusion with hepatic protective solution in dogs.

Temporary occlusion of hepatic inflow is a useful maneuver to reduce hemorrhage from liver trauma and difficult hepatic resections. The liver can be protected with a hepatic protective solution before inflow occlusion, just as the stopped heart is protected by a cardioplegic solution during open heart surgery. Twenty dogs were divided into two groups. The portal inflow of group A was infused via the mesenteric venous branch with a hepatic protective solution composed of 250 mg of hydrocortisone, 15 mEq of KC1, 6 mL of 0.1 N HC1, 5 mL of 10% magnesium sulfate and 250 mg of dextrose in one liter of cold lactated Ringer's solution. Group B was infused with cold lactated Ringer's solution as a control. The hepatic artery and portal vein were isolated and then clamped for 30 minutes. The elevation of serum GOT and GPT after release of the clamps was significantly greater in group B, especially during the first 48 hours. The levels of alkaline phosphatase and total bilirubin were also higher in group B until the 7th day. The results liver biopsies 3 hours after release of the clamps revealed marked congestion and destruction of hepatocytes in group B. We conclude that liver perfusion with a hepatic protective solution before inflow occlusion results in less damage to liver tissue and less impairment of liver function. Such protection is important in liver surgery.     

Placental vascular responses to nicardipine in the hypertensive ewe

Calcium channel blockers are arterial vasodilators effective in the treatment of hypertension. Therefore nicardipine, a dihydropyridine calcium channel blocker, should modulate angiotensin II-induced vasoconstriction. Regional blood flows were measured with radioactive microspheres in five chronically catheterized near-term ewes both before and 15 minutes after maternal infusion of angiotensin II at 5 micrograms/min. Nicardipine was then administered intravenously at 20 micrograms/kg/min over 2 minutes while the angiotensin II infusion was maintained. Blood flows were measured after 5 minutes. Maternal blood pressure levels were increased by angiotensin II from 83 +/- 4 mm Hg to 114 +/- 5 mm Hg, and were decreased to 70 +/- 4 mm Hg by nicardipine (p less than 0.05). Nicardipine also reversed angiotensin II-induced vasoconstriction in the renal and endomyometrial vascular beds (p less than 0.05). Unexpectedly, however, nicardipine worsened placental vasoconstriction caused by angiotensin II, as placental blood flow fell from 242 +/- 32 ml.min-1.kg-1 fetal weight to 128 +/- 7 ml.min-1.kg-1 fetal weight (p less than 0.05), and placental resistance increased from 0.48 +/- 0.04 mm Hg.ml-1.min.kg-1 fetal weight to 0.55 +/- 0.05 mm Hg.ml-1.min.kg-1 fetal weight (p less than 0.05). Nicardipine reverses angiotensin II-induced vasoconstriction systemically and in the kidney and uterus of the pregnant ewe, but does not reverse placental vasoconstriction and may significantly alter fetal cardiorespiratory status.     

Oxygen tension of the vaginal surface during sexual stimulation in the human

An oxygen electrode was maintained by suction on the vaginal wall in seven women. The basal value of pO2 was 9.3 mm Hg +/- 10.7 (mean +/- standard deviation) before clitoral self-stimulation was initiated. When stimulation took place the oxygen tension rose and peaked immediately after orgasm to 39.5 +/- 14.1 mm Hg. It then declined and fell to 20.1 +/- 13.8 mm Hg 10 minutes after the peak value. The changes correlate closely with changes in vaginal blood flow. The increased oxygen tension may be one of the factors that enhance of even initiate the motility of spermatozoa when deposited intravaginally.     

Cardiopulmonary effects of direct venous CO2 insufflation in ewes. A model for CO2 hysteroscopy

In order to mimic the delivery of CO2 into the pelvic circulation during sustained hysteroscopic surgery, direct insufflation of CO2 was done into the femoral vein of six anesthetized ewes. Following the establishment of baseline values in each animal, cardiac output, pulmonary arterial pressure (Ppa), pulmonary arterial wedge pressure (Ppw), arterial pH and gas levels, and ECG changes were recorded at ten-minute intervals. CO2 was delivered into the femoral circulation for 30 minutes. Following the experiment, measurements were repeated during a 20-minute recovery period. Ppa and Ppw increased significantly during the experiment but returned to baseline values after 70 minutes. Cardiac output, which increased significantly, remained high after the same period and was paralleled by cardiac rate. There was no significant change in systemic blood pressure or arterial oxygenation. Only at the highest flow rate were there observable changes in PCO2, accompanied by mild acidosis. One of the six animals displayed premature ventricular contractions at the inception of the highest flow rate. Since the delivery rate of CO2 per kilogram of body weight clearly exceeded that generally used in human hysteroscopic surgery (35-100 mL/min), these experimental results suggest that CO2, when employed as a distension modality in hysteroscopic surgery, displays a wide margin of safety.