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Background Various methods are used to assess the height of sensory block to touch under spinal anesthesia for cesarean section. We tested a novel, inexpensive, miniature, user-dependent plastic neurological wheel against the user-independent Neurotip mounted Neuropen. Methods Patients received either spinal or combined spinal–epidural anesthesia. For each patient assessment, the devices were randomly assigned to one of two independent investigators. The order of device application was randomly permuted. Neither researcher was involved with anesthetic care. At 5-min intervals for 20min after spinal injection, and again at the end of the operation, the levels of block to loss-of-touch sensation were assessed. While one investigator evaluated the block, the other left the operating room and vice versa. Mixed-effects regression and Bland–Altman analysis were used to weigh agreement between devices. Results The mean difference in level-to-touch was 0.04 (95% CI −0.18, 0.27) dermatome levels. Measurement error standard deviation associated with the Neurotip mounted Neuropen and plastic neurological wheel was 1.36 (95% CI 1.26, 1.41) and 1.33 (95% CI 1.26, 1.46) dermatome levels, respectively. The difference in measurement error standard deviation was −0.03 (95% CI −0.16, 0.24). This evidence excludes the possibility, with 95% confidence, of clinically significant bias or measurement error differences between methods. Occasional wide variances in dermatome level were observed with both instruments at the initial assessment only. Conclusion The compact plastic neurological wheel is as clinically reliable as the Neurotip mounted Neuropen.

Placental delivery is the only known cure for early onset preeclampsia, a major cause of maternal and neonatal morbidity and mortality worldwide. Prolonging pregnancy beyond 25weeks without undue maternal risk favors fetal survival, improves neonatal outcome and saves money. In vitro experiments using human placental tissue and in vivo studies employing "preeclamptic" animal models reveal the presence of likely druggable targets, especially within the maladapted intracellular nucleotide transduction pathways of preeclampsia. This review focuses on some novel pharmacological treatment options targeting early onset severe preeclampsia. Human and animal derived experimental data support the possible roles of nitric oxide donors (glyceryltrinitrate), aspirin, dietary supplements (calcium, l-Arginine, anti-oxidant vitamins), phosphodiesterase-5 inhibitors, statins, carbon monoxide and most recently, hydrogen sulfide. Extension of pregnancy or improvement of the disorder using means applicable in under resourced areas of the world would have a major positive impact on women's health globally. We therefore advocate the immediate launch of clinical trials testing simple innovative therapies in large obstetric units of developing countries such as South Africa or Brazil where preeclampsia is endemic and a regular killer of both mothers and offspring.

BACKGROUND Vasoactive agents administered to counter maternal hypotension at cesarean delivery may theoretically intensify the hypoxemic fetoplacental vasoconstrictor response and, hence, negatively impact transplacental oxygen delivery to the fetus. Yet, this aspect of their pharmacodynamic profiles is seldom mentioned, let alone investigated. We hypothesized that vasopressin, a potent systemic vasoconstrictor, and oxytocin, a uterotonic agent administered routinely at cesarean delivery, which, in contrast to vasopressin, possesses significant systemic vasodilator properties, would not influence distal stem villous arteriolar resistance. METHODS The dual-perfused, single, isolated cotyledon, human placental perfusion model was used to examine the resistance response of the fetoplacental circulation to oxytocin and vasopressin in placentae harvested from healthy women. Twelve of a total of 17 individual experiments were conducted successfully during which either oxytocin (n = 6) or vasopressin (n = 6) was introduced into the fetal reservoir in concentration increments of 10 M. Fetoplacental distal stem villous arteriolar perfusion pressure (FAP) was measured continuously. The fetal circuit concentration of either oxytocin or vasopressin was raised in a stepwise fashion from 10 to 10 M or 10 to 10 M, respectively. Both reservoirs were then purged of drug, after which 1-mL 1.0 mM 5-hydroxytryptamine (2.5 µM), an agent well known to manifestly increase fetoplacental distal stem villous arteriolar resistance, was introduced into the fetal circuit. A significant increase in FAP from baseline in response to exposure to 5-hydroxytryptamine confirmed that the fetoplacental vasoconstrictor response remained reactive. The primary outcome of this study was changes in FAP after incremental dosing of vasopressin and oxytocin. RESULTS No changes in FAP were observed with either oxytocin or vasopressin regardless of the drug concentration tested. For each drug and concentration, a mean pressure change greater than ±10 mm Hg was excluded with 95% confidence. In contrast, 5-hydroxytryptamine significantly increased perfusion pressure in all 12 successful experiments. CONCLUSIONS Oxytocin and vasopressin do not influence human fetoplacental distal stem villous arteriolar resistance. The neutral impact of vasopressin noted here is thus analogous to the reported negligible influence of the drug on human pulmonary arteriolar resistance. Neither drug seems likely to adversely influence the compensatory hypoxemic fetoplacental vasoconstrictor response.

Advances in experimental techniques for determination of transition moment directions in large molecules call for evaluation of the reliability of angles calculated using the semiempirical SCF-CI PPP method. Two disturbing features are considered: first, the large difference between oscillator strengths calculated by the dipole length and dipole velocity methods; second, the considerable effect of more highly excited configurations on the calculated transition moments and gradients. The two problems can be handled simultaneously if matrix elements of the linear momentum operator are obtained from the resonance integrals, since then the two operators give identical answers using wave functions derived from complete configuration interaction (CI). Numerical investigation on model systems is made of the extent of CI needed for such convergence. For strong transitions, results for polarization directions already reach their limiting values when very limited CI is performed.

We investigated the characteristics of hypoxemic fetoplacental vasoconstriction (HFPV) in the dual perfused, single isolated human placental cotyledon. Fetal arterial blood pressures (FAP) were measured in four cotyledons (Group 1) equilibrated with 21% oxygen (O2), 5% carbon dioxide (CO2), and nitrogen (N2) [control] followed by 5% CO2 in N2 for 30 min. FAP (mean +/- sd) increased from 69.8 (+/- 6.4) to 105 (+/- 3.0) mm Hg (P < 0.05), confirming the utility of HFPV in the human placenta. Eight more cotyledons (Group 2) were exposed sequentially and alternately at 15-min intervals to the control gases and to gas blends containing 15%, 12%, 5%, and 0% O2 with 5% CO2 and N2. FAP increased significantly (P < 0.05) in a stepwise fashion from 68.7 (+/- 3.7) to 70.5 (+/- 3.3) mm Hg with 15% O2; from 69.3 (+/- 3.8) to 72.4 (+/- 4.3) mm Hg with 12% O2; from 67.8 (+/- 3.2) to 74.5 (+/- 3.4) mm Hg with 5% O2; and from 69.7 (+/- 3.4) to 77.9 (+/- 5.9) mm Hg with 0% O2, suggesting that HFPV is a graduated response to reduced O2 conditions in the human placenta.

The pathogenesis of preeclampsia stems from aberrant changes at the placental interface. The trophoblastic endovascular invasion of tonic spiral arteries that converts them to passive conduits falters. Uteroplacental insufficiency and fetoplacental hypoxemia result. Secondary maternal oxidative stress and an excessive inflammatory response to pregnancy generate the clinical syndrome of preeclampsia. Current treatment focuses on preventing seizures, controlling hypertension, preserving renal function and delivering the baby. We propose that the pathophysiological changes induced by preeclampsia in the placenta parallel those caused by persistent hypoxemia in the lungs at high altitude or with chronic obstructive pulmonary disease. Unrelenting pulmonary hypoxic vasoconstriction induces pulmonary hypertension and cor pulmonale. Inhalation of nitric oxide and phosphodiesterase-5 inhibitors opposes pulmonary hypoxic vasoconstriction, alleviates pulmonary hypertension and improves systemic oxygenation. Notably nitric oxide donor therapy also counters hypoxemic fetoplacental vasoconstriction, a biological response analogous to pulmonary hypoxic vasoconstriction. Fetal oxygenation and nutrition improve. Placental upstream resistance to umbilical arterial blood flow decreases. Fetal right ventricular impedance falls. Heart failure (cor placentale) is avoided. Emergency preterm delivery can be postponed. Other than low dose aspirin and antioxidants vitamins C and E no available therapy specifically targets the underlying disease profile. We hypothesize that, like nitric oxide donation, pharmacological inhibition of placental phosphodiesterase-5 will also protect the fetus but for a longer time. Biological availability of guanosine 3'5'-cyclic monophosphate is boosted due to slowed hydrolysis. Adenosine 3'5'-cyclic monphosphate levels increase in parallel. Cyclic nucleotide accumulation dilates intact tonic spiral arteries and counters hypoxemic fetoplacental vasoconstriction. Intervillous and intravillous perfusion pick up. Maternal to fetal placental circulatory matching improves. Enhanced placental oxygen uptake alleviates hypoxemic fetal stress. Appropriate fetal nutrition resumes. Cor placentale and severe intrauterine growth restriction are averted. Increased maternal cyclic nucleotide concentrations promote systemic vasodilatation so that blood pressures fall. Preemption of oxidative stress initiated by "consumptive" oxidation of nitric oxide stabilizes the vascular endothelium and corrects coagulopathy. Anti-inflammatory and immunosuppressant adenosine 3'5'-cyclic monphosphate offsets the extreme gestational inflammatory response. Cellular injury and multi-organ damage are prevented. One tablet a day of the new long acting phosphodiesterase-5 inhibitor, tadalafil (half life of 17.5 h) theoretically should allow a preterm pregnancy affected by preeclampsia to continue safely. Selective monitoring of vital organ functions guards against life-threatening maternal complications. Regular biophysical profiling warns the obstetrician of impending fetal compromise. Fetal growth and vital organ maturation can continue. As a result workloads imposed upon neonatal intensivists will lighten. Parental anxiety and concern will be allayed. The cost of treating preeclamptic mothers and their extremely low birth weight infants will decrease. Money saved by midwifery services in poorer states can be used to pay for better prenatal care. Severe preeclampsia/eclampsia will be less common. Maternal and perinatal morbidity and mortality will be reduced. Because the human immunodeficiency virus often infects individuals at a workforce eligible age, the global acquired immunodeficiency syndrome pandemic has already brought many nations to the brink of economic ruin. Potentially productive lives saved for the future will help restore them fiscally.

Dear Editor,Samangaya and her colleagues are to be commended for having the courage to have “… safely conducted a clinical trial of a drug not routinely used during pregnancy” (1). They have thus t...

Study Objectives: To evaluate the transfer properties of methohexital and the influence of protein binding using the in vitro human placental perfusion model. Design: Fresh term human placentae from healthy parturients were perfused bidirectionally via a cannulated fetal chorionic artery and vein and needles placed into the maternal intervillous space. Maternal-to-fetal (M→F) and fetal-to-maternal (F→M) transfer and ultimate distribution of methohexital was investigated using a closed (recirculating) placental perfusion model. Setting: Obstetric anesthesia laboratories of two university medical centers. Patients: No patient participation occurred as placentae were obtained after delivery. Intervention: M→F and F→M transfer of methohexital was compared in vitro in perfusates with equal protein concentrations (2 g/100 mL in both perfusates) or albumin-simulated physiologic protein binding concentrations (maternal 8 g/100 mL; fetal 4 g/100 mL). Measurements and Main Results: Data obtained consisted of measurements of methohexital and antipyrine concentrations by high-performance liquid chromatography. Glucose and lactate concentrations and perfusate loss were measured to assess placental viability. Methohexital protein binding was assessed at 2, 4, and 8 g/100 mL of albumin by equilibrium dialysis. The transfer index of 0.83 ± 0.11 for the M→F perfusions was significantly greater ( p ≤ 0.05) than in the F→M direction (0.61 ± 0.04) when albumin concentration was equal in both perfusates. This transfer asymmetry disappeared when albumin concentrations simulating maternal (8 g/100 mL) versus fetal (4 g/100 mL) protein concentrations in the perfusate were used (M→F 0.87 ± 0.12 and F→M 0.95 ± 0.11). Conclusion: Methohexital readily crosses the placenta in both directions. Protein binding has significant effects on the degree of transfer of methohexital at any time when compared with antipyrine and its ultimate fetal/maternal distribution.

The LCAO version of the perimeter model with overlap through second order is used to obtain algebraic solutions for the singlet electronic states of the antiaromatic 4N-electron [n]annulenes of Dnh symmetry. The states of these biradicals are classified and their spectroscopic properties derived. General simple results are given for the signs and magnitudes of the A, B and C terms in magnetic circular dichroism. The effects of perturbations that preserve the antiaromatic biradical or biradicaloid character are considered. Other perturbations will be treated in Parts 2 and 3.

Geometries of A4X10 molecules (A = C, Si; X = H, F, Cl, Br, CH3, SiH3) have been optimized at the HF/6-31G* level as a function of the AAAA dihedral angle ω. In addition to the generally known gauc...

It is generally believed that bolus injections of local anesthetic through an epidural needle produce a more rapid onset of blockade, but at the expense of an increased incidence and severity of hypotension, whereas intermittent injections through a catheter take longer to achieve adequate anesthesia but with a lower risk of hypotension. The present study investigated two commonly used needle and catheter epidural injection techniques for differences in speed of onset of surgical anesthesia and incidence and severity of hypotension. Term parturients scheduled for elective cesarean section were randomized into two groups to receive epidural anesthesia with intermittent injection either through the epidural needle (n = 44) or via a previously placed catheter (n = 44). The incidence and severity of hypotension was similar in the two groups. No significant difference was found for the time to onset of surgical anesthesia. In the absence of benefits of needle injection, incremental catheter administration of local anesthetic with its multiple safety advantages is the technique of choice for induction of epidural anesthesia for cesarean section.

Background Fetal acidemia increases umbilical venous bupivacaine concentrations in the in situ rabbit model. The authors studied the effects of decreasing fetal pH on the rate of maternal to fetal (M-->F) clearances of lidocaine, bupivacaine, 2-chloroprocaine, and antipyrine (a nonionic marker of placental transfer) across the isolated, dual perfused, human placental cotyledon. Methods Maternal to fetal clearances of bupivacaine, lidocaine, 2-chloroprocaine, and antipyrine were determined at fetal pH (7.4), during progressive fetal acidemia (pH 7.2-->7.0-->6.8), and after recovery to fetal pH 7.4 in experiments with both low protein state and in those with in vivo maternal and fetal protein-binding potentials. Results Placental transfer of all three agents increased linearly as the fetal pH decreased. Antipyrine transfer was unaffected. Clearance of lidocaine and bupivacaine, but not 2-chloroprocaine, returned to baseline when fetal pH was restored to 7.4. When maternal and fetal protein-binding potentials were increased, clearance at fetal pH 7.4 of bupivacaine, but not lidocaine, decreased significantly. During fetal acidemia, the transfer of both agents increased, but to a lesser extent than in the low protein concentration experiments. Conclusions Increasing the pH difference between maternal and fetal perfusates promotes M-->F passage of unionized lidocaine, bupivacaine, and 2-chloroprocaine. This likely results from an increased proportion of ionized local anesthetic in the acidemic fetal perfusate and consequent widening of the M-->F concentration gradient of the unionized form. Transfer of lidocaine and bupivacaine was limited by the maternal protein binding.

Transition moment directions of mid-infrared transitions in four isotopomers of propene, CH2CHCH3, CH2CDCH3, CD2CHCD3, and CD2CDCD3, have been determined from linear dichroism spectra recorded in stretched polyethylene as solvent. The results were compared with expectations based on bond directions and with results of ab initio calculations at levels of approximations ranging up to CCSD/6-311G**. The former procedure is found to be unreliable, even for high frequency vibrations. With rare exceptions, the highest levels of ab initio theory agree with the experimental directions to within about ±20°, and for intense transitions, to within the experimental uncertainty of about ±(5−10)°.

Background Bupivacaine is widely used for obstetric analgesia, yet published information on the mechanism of human placental bupivacaine transfer is sparse. The dual perfused human placental model was used to elucidate the factors governing the placental transfer of bupivacaine. Methods Bupivacaine transfer was studied using the recirculating (closed) model and the single pass (open) model. Single placental cotyledons were perfused with either heparinized Krebs-Ringer's buffer (KRB) supplemented with human albumin (fetal and maternal circuits) or 100% fresh frozen plasma (maternal circuit) to control the bupivacaine protein binding in those circuits. In the open model, bupivacaine clearance was compared before and after being subjected to either increasing concentrations of bupivacaine or its structural analog, mepivacaine. Results For those studies in which the maternal and fetal protein binding was equal, the maternal to fetal (M-->F) transfer was significantly greater (P < 0.05) than that in the fetal to maternal (F-->M) direction. When the perfusates were modified to simulate actual in vivo plasma protein concentrations, bupivacaine transfer was shown to be related to the degree of protein binding found in the two circuits. In the open studies, bupivacaine transfer was similar at all concentrations investigated, unaffected by mepivacaine, and related to the pH of the fetal perfusate. A concentration effect was seen within the placental tissue at the end of the experiment. Conclusions Bupivacaine placental transfer characteristics suggest passive diffusion rather than active drug transport and appear to be influenced by the maternal and fetal plasma protein binding, fetal pH, and placental uptake.

This study defines human placental transport of cocaine and its two minor, but pharmacologically active, metabolites--norcocaine and cocaethylene. The experimental system was the single, isolated perfused cotyledon of a normal term human placenta, and antipyrine served as a freely diffusible marker. Cocaine was transferred rapidly by the placenta at a rate about 80% that of antipyrine. The transfer had characteristics of passive transport consistent with the high lipid solubility of the drug. We found no evidence of significant placental metabolism of cocaine during its rapid placental transfer. Ethanol did not alter the cocaine transfer rate. Norcocaine and cocaethylene were equally as rapidly transferred. Thus the placenta is no barrier to the transfer of cocaine and its derivatives to the fetus.

Vibrational transition moment directions of s-trans-1,3-butadiene were deduced from measurements of its IR linear dichroism on samples partially oriented (i) by photoselective photoiosomerization of s-cis-1,3-butadiene isolated in inert-gas matrices with linearly polarized light, (ii) in stretched polyethylene, and (iii) in stretched poly(ethylene-d 4 ). The moment directions are in quite good agreement with those predicted by theory at the MP2/6-311G** level of approximation. For two plausible mechanisms of s-cis to s-trans isomerization, it predicts the observed near coincidence of the C 1 -C 4 directions. For another reaction path, it predicts a 30 o angle between them. However, at present, it is unknown whether matrix photoisomerizations indeed proceed without exertion of a net torque on the environment

Information on the potential-energy surfaces of the ground and 1σσ* excited states of oligosilane chains, collected from experimental and theoretical sources, is discussed in terms of electronic structure and the mechanisms of bond and excitation delocalization.

GVB/[5s3p1d/3s1p] energies were calculated for 31 geometries of cyclobutadiene in the D2h point group. These geometries differed in the values of the symmetrized internal coordinates for two CC stretching and one CCH bending modes. The data points were fitted to the expansions of in powers of . Variational calculations provided the following energies of the lowest Ag vibrational levels (with respect to the vibrational ground state): 4.4; 1161.2; 1162.3; 1304.0; 1322.8; 1920.3; and 1991.0 cm−1.

Cardiovascular malformations were examined for white/black variation in the Baltimore-Washington Infant Study. In this population-based case-control study, cases (n = 2,087) were live births with cardiovascular malformations ascertained through pediatric cardiology centers and 53 hospitals in Maryland, the District of Columbia, and northern Virginia between 1981 and 1987. Controls (n = 2,721) were a random sample of infants from the live-birth cohort that gave rise to the cases. The proportion of infants that were white was similar for all cases as a group and controls (0.68 and 0.67, respectively). Subgroup analysis, however, revealed an excess of white infants among cases with Ebstein's anomaly (odds ratio (OR) = 3.7, 95% confidence interval (Cl) 1.1-12.5), aortic stenosis (OR = 3.6, 95% Cl 1.7-7.6), pulmonary atresia (OR = 2.5, 95% Cl 1.0-6.1), coarctation of the aorta (OR = 2.2, 95% Cl 1.4-3.5), and D-transposition of the great arteries (OR = 1.6, 95% Cl 1.1-2.5), and a deficit of white infants among cases with pulmonary stenosis (OR = 0.6, 95% Cl 0.4-0.8) and heterotaxia (OR = 0.4, 95% Cl 0.3-0.8). These associations remained when cases were stratified by infant's age or by method of diagnosis. Controlling for socioeconomic factors attenuated the white excess for Ebstein's anomaly (OR = 3.0, 95% Cl 0.9-10.5), disclosed a white excess among cases of L-transposition of the great arteries (OR = 2.8, 95% Cl 1.0-8.0), and revealed that the white excess for aortic stenosis was limited to low and middle socioeconomic strata. These results highlight racial variations in cardiovascular malformations, suggest that socioeconomic factors account for some of this variation, and identify malformation subgroups for which further evaluation of sociocultural, environmental, and familial factors is needed.

Vibrational transition moment directions of s-trans-1,3-butadiene were deduced from measurements of its IR linear dichroism on samples partially oriented (i) by photoselective photoiosomerization of s-cis-1,3-butadiene isolated in inert-gas matrices with linearly polarized light, (ii) in stretched polyethylene, and (iii) in stretched poly(ethylene-d 4 ). The moment directions are in quite good agreement with those predicted by theory at the MP2/6-311G** level of approximation. For two plausible mechanisms of s-cis to s-trans isomerization, it predicts the observed near coincidence of the C 1 -C 4 directions. For another reaction path, it predicts a 30 o angle between them. However, at present, it is unknown whether matrix photoisomerizations indeed proceed without exertion of a net torque on the environment

Factors affecting lidocaine transfer across the normal term human placenta were studied using the dual perfused isolated single cotyledon. Experiments were performed using perfusates which provided equal protein binding in both the maternal and fetal circuits as well as perfusates that approached the actual in vivo maternal/fetal protein binding gradient. Additional experiments were performed to investigate the effects of increasing maternal lidocaine concentration (5, 10, 40, 80 microg/mL) on maternal to fetal (M--F) lidocaine transfer across the human placenta. Lidocaine crossed the placenta rapidly in both the M--F and fetal to maternal (F--M) directions. When protein binding was similar in the two circuits, M--F transfer ratios (lidocaine transfer/antipyrine transfer) were significantly lower than the transfer ratios seen in the F--M direction (0.59+/-0.04 versus 0.84+/-0.06, P0.05). Transfer ratios (M--F: 0.83+/-0.06, F--M: 0.96+/-0.06) were not reduced when the physiological maternal/fetal protein binding gradient was present. Lidocaine transfer was not diminished by increasing maternal concentrations and, in contrast to bupivacaine, was not significantly affected by its binding.

We studied the effects of 5 vasopressors on fetal arterial perfusion pressure (FAP) in vitro using the dual perfused, single isolated cotyledon, human placental model.In 29 separate experiments, epinephrine (75 mg), norepinephrine (75 mg), ephedrine (50 mg), phenylephrine (2 mg), and methoxamine (40 mg) were introduced into the 250-mL reservoir serving the maternal perfusion circuit to determine the effect of each drug on FAP. The duration of drug exposure for each placental cotyledon was approximately 180 minutes.After 180 minutes, FAP (mean +/- sd) increased significantly with ephedrine from 64 +/- 3 to 172 +/- 71 mm Hg (P0.001) and with phenylephrine from 81 +/- 4 to 132 +/- 11 mm Hg (P = 0.003). No changes in FAP were seen with epinephrine, norepinephrine, and methoxamine.In the dual perfused, single isolated cotyledon, human placental model, exposure of the maternal circulation to ephedrine and phenylephrine caused an increase in FAP, whereas exposure to norepinephrine, epinephrine, and methoxamine did not. The pharmacodynamic mechanisms underlying these differences have yet to be explained. Thus, the clinical implications of the findings are as yet unclear.

Infrared and ultraviolet spectra of the gauche and anti conformers of matrix-isolated permethyl-n-tetrasilane have been obtained separately by taking advantage of thermally induced gauche-to-anti conversion and of wavelength-selective photochemical destruction of either conformer. The resolved UV spectrum of the gauche conformer provides the first piece of experimental evidence in favor of the recently proposed reinterpretation of conformational effects on tetrasilane electronic states. According to this, it is not the energy but the intensity of the lowest singlet excitation that changes dramatically as the SiSiSiSi dihedral angle is varied, as a result of an avoided crossing between s̀s̀* and s̀π* states. Implications for the general understanding of sigma conjugation in simple terms are discussed. Unconstrained MP2/6-31 G* optimization predicts the existence of a third backbone conformer (ortho), with a dihedral angle of about 90°. Its predicted (HF/3-21 G*) mid-IR spectrum is indistinguishable from that of the gauche conformer, and the matrix-isolation spectra thus provide no evidence for or against its presence.

UNLABELLED This study compares the placental transfer of ropivacaine and bupivacaine using the dual perfused, single cotyledon human placental model. We studied the effects of maternal/fetal protein binding, maternal ropivacaine concentration, and fetal pH on ropivacaine transfer. At a clinically relevant maternal concentration (1 microg/mL), the calculated transfer ratios (local anesthetic percent transfer/antipyrine percent transfer) of ropivacaine (0.82 +/- 0.03) and bupivacaine (0.74 +/- 0.01) were comparable at the completion of the perfusion experiment (120 min). When the perfusates were modified to simulate actual in vivo plasma protein binding values, the maternal-to-fetal transfer of ropivacaine and bupivacaine decreased significantly (P < 0.05) as indicated by transfer ratios of 0.42% +/- 0.07% and 0.40% +/- 0.03%, respectively. No saturation of the transfer process was observed for either drug at the maternal concentrations investigated. The placental transfer of both local anesthetic agents increased significantly as the fetal pH decreased. This investigation shows that ropivacaine and bupivacaine cross the human placenta at a similar rate, despite their differences in lipophilicity and stereochemistry. Placental transfer of both compounds is highly influenced by maternal and fetal protein concentration and the fetal pH. IMPLICATIONS The placental transfer of ropivacaine was shown to be similar to that of bupivacaine, and is thus highly influenced by the degree of maternal and fetal protein binding and fetal pH.

Information on the potential-energy surfaces of the ground and 1σσ* excited states of oligosilane chains, collected from experimental and theoretical sources, is discussed in terms of electronic structure and the mechanisms of bond and excitation delocalization.