Alexander D. Kofinas

Maternal and fetal β-endorphin release in response to the stress of labor and delivery

In order to clarify the stress effect of labor on maternal and neonatal plasma levels of β-endorphin, we measured this peptide in samples taken from 40 pregnant patients and their neonates at the time of normal vaginal delivery (n = 15), and at cesarean section performed either in early labor (n = 13) or prior to labor (n = 12). The mean (± SE) maternal plasma concentration of β-endorphin in the vaginal delivery group was 40.3 ± 5.6 fmol/ml, which was significantly higher than that in their neonates (21.3 ± 2.9 fmol/ml). In contrast, maternal levels of β-endorphin in the cesarean section groups (8.2 ± 1.2 and 8.5 ± fmol/ml) were significantly lower than those in their neonates (23.3 ± 5.6 and 15.6 ± 2.8 fmol/ml). Concentrations of β-endorphin in mothers delivered vaginally were also significantly higher than those in mothers delivered by cesarean section. However, there was no difference in mean cord levels of β-endorphin among the three groups. These findings indicate that (1) neither the presence or absence of labor affects fetal plasma β-endorphin secretion and (2) the stress of labor and delivery produces a marked increase in maternal release of β-endorphin.

Interrelationship between atrial natriuretic factor concentrations and acute volume expansion in pregnant and nonpregnant women

The secretion of atrial natriuretic factor by human atrial myocytes is stimulated by increased intraatrial pressure or atrial distention. To determine whether acute intravascular volume expansion affects atrial natriuretic factor concentrations during pregnancy, circulating atrial natriuretic factor levels were measured in pregnant women at term (before elective cesarean section) and nonpregnant control subjects before and during intravenous infusion of lactated Ringers solution (approximately 30 ml/kg). Venous plasma concentrations of alpha-human atrial natriuretic factor were determined by a specific radioimmunoassay. A significant increase in alpha-human atrial natriuretic factor levels in nonpregnant subjects was seen. Pregnant women did not show a significant response to a similar stimulus. Finally, basal alpha-human atrial natriuretic factor levels in pregnant and nonpregnant women were not different. Volume expansion (long-term or short-term) in normal human pregnancy may not be sensed by atrial volume sensors, possibly because it is accommodated by an enlarged maternal vascular compartment.

Real-time optical imaging of experimental brain ischemia and hemorrhage in neonatal piglets.

Abstract Our objective was to study the development of experimental brain ischemia and hemorrhage by real-time optical imaging. Optical imaging is based on the ability of near infrared light to non-invasively penetrate through the intact scalp and skull and measure brain concentrations of oxy- and deoxyhemoglobin, dominant brain absorbers. Optical imaging was performed in 7 anesthetized, instrumented, and ventilated newborn piglets subjected to the injection of 0.3 cc of saline followed by 2 cc of blood into the left frontal subcortical brain region via a needle inserted through the skull with stereotactic guidance. The image-acquisition rate of 5.26 images per sec allowed for real-time imaging. The detection threshold of the imager at the estimated depth of 1–1.5 cm was ∼, 70 μL for saline and ∼,40 μL for blood. The imager readily detected five subcortical hematomas and two large bilateral subarachnoid hemorrhages. The imager detected a global decrease in brain absorption associated with the volume-injection-related increase in intracranial pressure in the surrounding ipsi- lateral and contralateral brain. Any decrease in brain absorption is an equivalent to brain ischemia. This study demonstrates the capability of optical imaging in detecting brain ischemia and hemorrhage in real-time with high temporal and spatial resolution.

Role of frequency domain optical spectroscopy in the detection of neonatal brain hemorrhage — A newborn piglet study

OBJECTIVE Inability of continuous wave (CW) optical spectroscopy to measure changes in scattering, and the use of an arbitrary rather than an actual baseline, makes the CW method highly susceptible to errors that can lead to a false-positive or false-negative diagnosis. Our objective was to assess whether, and to what extent, the use of quantitative frequency domain spectroscopy would improve our ability to detect and monitor the development of brain hemorrhage. METHODS A dual-channel frequency-domain tissue spectrometer (Model 96208, ISS, Inc., Champaign, IL) was used to monitor the development of experimental subcortical and periventricular-intraventricular hemorrhage (IVH) in 10 newborn piglets (blood injection model). The multidistance approach was employed to calculate the absorption and reduced scattering coefficients and hemoglobin changes from the ac, dc, and phase values acquired at four different source-detector distances and at 752 nm and 830 nm. RESULTS There were significant absorption and scattering changes in the subcortical hematoma (n = 5) and the IVH groups (n = 5). The smallest detectable amount of blood in the brain was 0.04 ml. Changes associated with subcortical hematoma were several times higher than those associated with IVH, and correlated better with the estimated cross-sectional area of the hematoma than with the volume of the injected blood. As opposed to IVH, there was a significant absorption difference between the injured (subcortical hematoma) and normal side of the brain, probably because in case of IVH a significant volume of the injected blood had accumulated/spread beyond the reach of the probe. CONCLUSION Clearly, frequency-domain spectroscopy cannot increase our ability to quantify the volume (size) or the oxygenation of the injected blood, especially in the case of IVH. However, the ability to quantify the baseline tissue absorption and scattering would significantly improve diagnostic performance, and may allow for early identification and treatment of neonatal brain hemorrhage.

Placental Laterality May be a Random Event and Not the Result of Inherent Uterine Artery Pathology

OBJECTIVE To determine whether placental laterality and discordant uterine artery impedance during pregnancy is a random event or the result of uterine artery pathology. METHODS We identified 50 patients with unilateral placenta and pathologic uterine artery impedance during their current pregnancy and enrolled them in the study. Thirty-three of these patients met the inclusion criteria and returned during the first 10 days of their third normal menstrual cycle after delivery. We examined the pelvic anatomy to rule out any pelvic pathology and then used color and pulsed wave duplex Doppler to identify the uterine artery in the immediate vicinity of the paracervical area at the level of the isthmus. We obtained the uterine artery resistance index (RI) from each uterine artery. We performed statistical analysis by means of t-test. RESULTS The uterine artery ipsilateral to the placenta exhibited significantly lower impedance than the contralateral in the pregnant state. When the placenta was right, the values (mean +/- SD) were 0.60 +/- 0.11 vs. 0.73 +/- 0.09 for the right and left artery, respectively. When the placenta was left the values were 0.57 +/- 0.08 vs. 0.77 +/- 0.07 for the left and right uterine artery, respectively. In the nonpregnant state, the corresponding values were 0.90 +/- 0.04 vs. 0.90 +/- 0.05 and 0.91 +/- 0.05 vs. 0.90 +/- 0.04, respectively. CONCLUSION In patients with a unilateral placenta and discordant pathological uterine artery impedance during pregnancy, there is no evidence of discordant impedance between the two uterine arteries in the postpartum period. We speculate that the location of placental implantation may not be the result of preexisting uterine artery discordant impedance.

Effect of placental laterality on uterine artery resistance and development of preeclampsia and intrauterine growth retardation

We studied 153 pregnant women with normal pregnancies and 147 women with complicated pregnancies (diabetes, hypertensive disorders, and intrauterine growth retardation) to evaluate the association of placental location and the development of preeclampsia, intrauterine growth retardation, and uterine artery resistance. The placental location was determined by real-time ultrasonography, and the uterine artery resistance was determined by continuous-wave Doppler flow velocity waveform analysis. In the presence of preeclampsia or intrauterine growth retardation, up to 75% of the patients had unilaterally located placentas and 25% central placentas, whereas in the absence of these two conditions only 51% of the patients had unilateral and 49% central placentas (p less than 0.02). In patients with unilateral placentas, the incidence of preeclampsia and intrauterine growth retardation was 2.8-fold and 2.7-fold greater than in patients with central placentas (p less than 0.03 and p less than 0.01). Among all patients unilateral placental location was more likely to be associated with abnormal artery flow velocity waveforms than central placental location (p less than 0.001). We conclude that unilateral placental location may predispose to the development of preeclampsia and intrauterine growth retardation by its effect on uterine artery resistance.