Deborah L. Reid

The pathophysiology of the anophthalmic socket. Part II. Analysis of orbital fat.

The pathophysiologic mechanisms responsible for the clinical features of the anophthalmic socket are poorly understood. Atrophy of orbital fat has been thought to be a major contributing cause of enophthalmos and the superior sulcus deformities that develop after enucle-ation, but it has never been demonstrated histopathologically or confirmed by scientific analysis. This study was undertaken to investigate the changes that occur in the orbital fat compartment of the anophthalmic socket in an animal model by measuring orbital soft tissue mass and evaluating adipocyte cell size. Instead of reduction in the tissue mass, a statistically significant greater weight of the fat and connective tissue compartment was found in the anophthalmic orbit by nearly 13% compared to the control orbit in the animals in the long-term group. No significant change in the mean maximal diameter of adipocytes developed 7 months after enucleation. These analyses do not support the concept that orbital fat atrophy or a reduction of metabolic activity occurs in the anophthalmic socket in this animal model. From these results and our previous findings that the circulation dynamics and blood flow to orbital tissues do not change after enucleation, we propose that the pathophysiologic basis of the problems associated with anophthalmos is a disturbance in the spatial architecture and interrelationships of the multiple tissue components of the orbit, not a change in the orbital blood flow or development of fat atrophy.

Spectral analysis of antepartum fetal heart rate variability from fetal magnetocardiogram recordings

Fetal heart rate variability was derived from fetal magnetocardiogram recordings in ten subjects at gestation ages 32-38 weeks. Maternal interference was negligible and R-wave detection was highly reliable. Oscillations suggestive of respiratory sinus arrhythmia (RSA) were prominent in many of the heart rate tracings. Spectral analysis was used to quantify heart rate variability and to examine the influence of the RSA-like oscillations on heart rate variability. The oscillations were associated with increased power in the frequency range 0.4-1.0 Hz (P < or = 0.05). Magnetic recording appears to offer significant advantages for investigation of beat-to-beat fetal heart rate throughout the latter stages of pregnancy.

Fetal heart rate variability and behavioral state: Analysis by power spectrum

OBJECTIVE We attempted to determine the relationship between the fetal heart rate power spectrum and fetal state. STUDY DESIGN Interbeat intervals, electrocortical activity, and fetal breathing movements were recorded from five near-term fetal lambs. Interbeat intervals were taken from epochs of low-voltage electrocortical activity with breathing, low-voltage electrocortical activity without breathing, and high-voltage electrocortical activity without breathing. Power spectral techniques were applied to determine the underlying frequencies contributing to fetal heart rate variability. Spectral analysis was also performed on fetal breathing data from three animals. RESULTS Significant differences were found between low-voltage electrocortical activity with breathing and high-voltage electrocortical activity without breathing at 0.62 Hz and from 1.09 to 1.56 Hz. There was no clear relationship between the breathing and heart rate spectra. CONCLUSIONS Fetal heart rate is mediated by both state and respiratory variables. The respiratory component is not strictly related to respiratory rate.

The pathophysiology of the anophthalmic socket. Part I. Analysis of orbital blood flow.

A wide variety of complications of the anophthalmic socket develop in patients after enucleation. including enophthalmos, superior sulcus deformities, eyelid malpositions, implant migration and extrusion, poor prosthetic motility, and socket contraction. Changes in the orbital blood flow and metabolic activity of the socket tissues and atrophy of the orbital fat occurring after enucleation have been suggested as two theoretical mechanisms that result in the development of these clinical conditions. Lack of scientific evidence and a limited understanding of the pathophysiologic basis of the features of anophthalmos led us to evaluate the validity of these proposed mechanisms in an animal model. Selected parameters of the normal orbits were compared with the contralateral anophthalmic orbits at different time intervals after surgery. Orbital blood flow was studied with selective ophthalmic artery angiography and radioactive microsphere techniques. Ophthalmic arteriography demonstrated symmetric caliber and filling characteristics of the major orbital vessels of the control and experimental orbits, although their topographic course was slightly more tortuous in the anophthalmic socket. Results of radioactive microsphere analysis of capillary blood flow per weight of the different orbital tissue compartments of the animals in the long-term group showed no significant difference between the normal and anophthalmic sockets. These findings provide evidence that the circulation dynamics and blood flow to orbital tissues do not change after enucleation surgery.

Differential effects of intravenous hydralazine on myoendometrial and placental blood flow in hypertensive pregnant ewes

OBJECTIVE The differential vasoactive effects of hydralazine on the uteroplacental vascular bed were studied. STUDY DESIGN After control measurements were taken, near-term chronically prepared pregnant sheep were continuously infused with angiotensin II. Maternal arterial pressure was increased by 32 mm Hg. Hydralazine was then administered; the effects on regional resistance and blood flow were evaluated with a radionuclide-labeled microsphere technique. Analysis of variance for repeated measures was used to compare observations. RESULTS When compared with the hypertensive state, hydralazine caused the following changes by 40 minutes (mean +/- SEM): Although maternal blood pressure fell 31% +/- 5% (p = 0.0005), placental blood flow was unchanged, total uteroplacental blood flow increased 24% +/- 8% (p = 0.03), total uteroplacental resistance decreased 43% +/- 4% (p = 0.0002), placental resistance decreased 19% +/- 9% (p = 0.01), myoendometrial blood flow increased 390% +/- 82% (p = 0.0005), and myoendometrial resistance decreased 82% +/- 4% (p = 0.0005). CONCLUSIONS In angiotensin II-induced hypertensive ewes, hydralazine is an effective dilator of the uteroplacental vascular bed and can maintain placental blood flow while blood pressure.

Dose-response curves of the uterine and placental vascular beds to prostaglandin I2

Local infusion of prostaglandin I2 (PGI2) has been reported to dilate the uteroplacental vasculature in a dose-dependent manner. In this experiment we attempted to distinguish the placental and nonplacental (uterine) components of this response over four concentrations of PGI2. Eleven near-term sheep were chronically instrumented for determination of regional blood flows by the use of radioactive microspheres. PGI2 was administered in a retrograde manner via a branch of the middle uterine artery at 1, 3, 10, and 20 micrograms/min. Flows were measured before (control) and after 5-minute infusions at each of the four concentrations (test). The uterine vasculature vasodilated in response to local PGI2 infusion. The 10 micrograms/min dose, for example, produced a mean (+/- SEM) flow of 0.70 +/- 0.07 ml/min/gm; the control value was 0.41 +/- 0.03 ml/min/gm (p less than 0.001). At 20 micrograms/min the test and control flows were 0.75 +/- 0.16 and 0.36 +/- 0.06 ml/min/gm (p less than 0.05), respectively. Uterine vascular resistance fell in a dose-dependent manner as well. There was no evidence of placental vasodilation at any of the doses tested. Renal vasodilation and decreased systemic arterial pressure at higher PGI2 doses suggest a recirculation effect. We conclude that PGI2 does not dilate the placental vasculature over the dose range of 1 to 20 micrograms/min and that the reported vasodilation of the uteroplacental vasculature is a result of decreased resistance in the uterine vasculature alone.

Effects of Forskolin on Placental Vascular Resistance in Rabbits

Abstract Forskolin is a direct stimulant of adenylate cyclase and increases cAMP production. It also acts as a vasodilator. To study the effect of forskolin infusion on rabbit maternal vascular resistance, we instrumented 11 pregnant rabbits with catheters in the left ventricle, jugular vein, and left and right femoral arteries. After a 2-day recovery period, one of two protocols was performed. In the control period of the first protocol (N = 6), 50% ethanol in saline was infused at 0.103 ml · min-1 for 5-min. Forskolin (10-3 M) in 50% ethanol was then infused for 5 min at 0.103 ml · min-1. After each infusion period, regional blood flows were measured by microsphere injection. Data are expressed as means ± SEM. Blood pressure decreased from 81 ± 3 to 79 ± 3 mm Hg, (P < 0.05, N = 10) during forskolin infusion. Total placental resistance fell from 180.3 ± 10.7 to 133.8 ± 12.0 mm Hg ± min ± ml-1 per gram, P < 0.05. Cerebral, coronary, and renal vascular resistance fell significantly. During the second protocol (N = 5), angiotensin II (0.05 μg ± min-1) was infused for 5 min followed by the addition of forskolin (10-3 M at 0.103 ml ± min-1) to the infusate. Regional blood flows, vascular resistances and blood pressures were determined. Blood pressure fell from 99 ± 6 to 92 ± 7 mm Hg (P < 0.05) when forskolin was added to the infusate. Placental resistance fell from 202.5 ± 21.6 to 158.0 ± 29.0 mm Hg · min · ml-1 per gram (P < 0.05). While cerebral vascular resistance did not change, renal and coronary resistances fell in response to forskolin. This study demonstrates that forskolin is able to dilate rabbit placental vessels alone and in the presence of the vasoconstrictive agent angiotensin II.

Uncoupling of excitation from contraction in uterine smooth muscle in near-term ewes

We infused forskolin in 30% ethanol or 30% ethanol systemically in seven chronically catheterized near-term sheep to determine the response of ovine uterine musculature to cyclic adenosine monophosphate stimulation. Maternal and fetal arterial pressure, fetal venous pressure, intrauterine pressure, and uterine electromyogram activity were monitored continuously. Prostaglandin E2 was infused at a delivery rate that caused a minimal 5 mm Hg increase in intrauterine pressure with definite contraction-like pressure spikes and associated uterine electromyogram activity. Forskolin (10 mg in 30% ethanol) or ethanol (vehicle) was then infused for 20 minutes. The prostaglandin E2 challenge was repeated 3 minutes later and again every 30 minutes over a 2 1/2-hour period. Data were analyzed by repeated measures analysis of variance. Infusion of ethanol (n = 2) had no apparent effect on either the intrauterine pressure or the uterine electromyogram response to prostaglandin E2 challenge. Forskolin infusion (n = 5) caused an attenuation of the intrauterine pressure response to prostaglandin E2 for 93 minutes. This effect was greatest 33 minutes after the infusion ended when the integrated pressure signal was 37% of the initial prostaglandin E2 response. The forskolin infusion had no effect on uterine electromyogram response to prostaglandin E2. We conclude that forskolin causes an uncoupling of excitation from contraction in the intact near-term ovine uterus.

Characterization of Uterine Contractures and Demonstration of Placental Vasodilation in the Mid-Gestation Albino Guinea Pig

Twenty-five mid-gestation guinea pigs were studied to determine the nature of spontaneous uterine contractures and elucidate the temporal relationship between blood flow and contractile activity. In the first protocol, 15 mid-gestation guinea pigs with indwelling vascular catheters were studied. Blood flows were measured by radioactive microsphere technique during rest, uterine contracture, and, in six animals, 1 minute after contracture activity. During contracture, maternal blood flow to the placenta closest to the electrode fell to 81.3 ± 5.3% of control (n = 15, P ±. 01) and then rose to 130.4 ± 10.2% of control (P ≤. 01) 1 minute after a contracture. The corresponding relationships were also significant for placental vascular resistance and constitute a reactive hyperemic response of the placenta to uterine contracture. No such phenomenon was observed in the more remote placentas on either the ipsilateral or contralateral side.To investigate the nature of contractile activity, electrodes were placed ...

Magnetic monitoring of fetal heart activity

We have measured fetal magneto-cardiograms in three subjects of gestation ages 33–37 weeks. Maternal interference was negligible in all recordings. Accurate measures of heart rate, beat-to-beat variability, and averaged MCG waveforms were derived. The results confirm that magnetic monitoring offers significant advantages for antepartum monitoring and deserves further investigation.