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Biomedical subjects

R J Morrow

Publications and source records attributed to R J Morrow.

At least 19 recordsLinked to original sources

Left ventricular hemodynamics in anemic fetal lambs.

OBJECTIVE: To assess the left ventricular determinants of cardiac output in 12 chronically instrumented fetal lambs, six of which where made anemic. METHODS: Twelve, singleton pregnant ewes were instrumented between 123-126 days gestation and chronic catheters placed in-situ. In six fetal lambs, isovolemic fetal anemia was induced (reducing the hematocrit from a mean of 35% to 20%). In a prospective study, absolute 'beat-to-beat' LV volumes and pressures were obtained (gestational age 131-134 days) using a conductance catheter method and a comparison made with non-anemic fetal lambs. RESULTS: The group of anemic fetuses (n = 6) had a significantly reduced hematocrit as compared to the control group (37% decrease: mean difference--13.4%; P < 0.001). The arterial blood gases of the two groups were not statistically different, with the exception of the pO2 and oxygen content which were significantly lower in the anemic group (P < 0.05). There was no significant change in fetal heart rate, LV preload (as assessed by venous pressure, end-diastolic volume and pressure) or mean arterial pressure between the anemic and control groups. However, a 75% increase in LV stroke volume was observed in the anemic fetal lambs (P < 0.05), secondary to a 61% fall in LV afterload (P < 0.05). There was no significant change in inherent myocardial contractility of the LV, although this did increase to approach statistical significance in the anemic group (P = 0.056). The diastolic time interval was increased by 22% in the anemic fetus, possibly allowing prolonged LV filling time. The indices measuring LV relaxation (Tau and dP/dtmin) were not significantly different in either group. CONCLUSIONS: This is the first study to report absolute left ventricular volumes in the anemic ovine fetus and the relationship of these data to LV pressure during the cardiac cycle. The model used produces a state of moderately severe, non-hydropic, isovolemic, fetal anemia consistent with those previously described. Although the anemic state was not prolonged, an observed increase in LV stroke volume (which is predominantly due to a decrease in afterload) has been described.

Anemia↗

Role of the L-arginine nitric oxide pathway in hypoxic fetoplacental vasoconstriction.

The role of nitric oxide in hypoxic fetoplacental vasoconstriction (HFPV) was investigated using dually perfused human placental cotyledons. Standard medium (Earle's salt solution with added dextran and L-arginine) was equilibrated with 95 per cent O2 and 5 per cent CO2 (maternal side) and 94 per cent N2 and 6 per cent CO2 (fetal side). Part 1 consisted of perfusion for 1 h, then maternal perfusate equilibrated with a 95 per cent N2 and 5 per cent CO2 for 20 min (hypoxia), and then the original perfusion conditions resumed for 40 min. In part 2, this sequence was repeated with standard medium alone (n = 6), or with added N-nitro-L-arginine methyl ester (L-NAME) (n = 6), or L-NAME and nitroglycerin (n = 6). When standard medium was used throughout, basal fetal perfusion pressure (30 +/- 2 mmHg) and the hypoxia-induced increase in perfusion pressure (18 +/- 1 mmHg) did not change significantly between parts 1 and 2. L-NAME increased basal perfusion pressure from 33 +/- 3 to 56 +/- 2 mmHg whereas perfusion pressure remained unchanged with L-NAME and nitroglycerin or nitroglycerin alone. The hypoxic vasoconstriction observed during part 1 in the L-NAME (14 +/- 3 mmHg) and the L-NAME with nitroglycerin groups (18 +/- 2 mmHg) was abolished during part 2 (to - 4 +/- 1 and 0.4 +/- 0.5 mmHg, respectively) whereas nitroglycerin alone significantly blunted the response (21 +/- 3 to 6 +/- 1 mmHg). Results suggest that a reduction in basal NO release mediates hypoxic fetoplacental vasoconstriction in the perfused human placental cotyledon in vitro.

Adult↗

Reduced placental villous tree elaboration in small-for-gestational-age pregnancies: relationship with umbilical artery Doppler waveforms.

OBJECTIVE: Our purpose was to investigate the three-dimensional architecture of placental villi from normal and growth-restricted fetuses and relate findings to umbilical artery blood flow velocity waveforms. STUDY DESIGN: Placentas from term (n = 15) and preterm (n = 5) appropriately grown and term (n = 9) and preterm (n = 7) growth-restricted fetuses (birth weight < 10th percentile) were examined to determine the number of arteries per stem villus and the three-dimensional configuration of the villous trees and their vessels. Umbilical blood flow before delivery was assessed by Doppler ultrasonography. The effects of age and growth restriction were determined by two-way analyses of variance. RESULTS: Growth restriction was associated with reduced large vessel wall thickness (p < or = 0.05) but no reduction in the number of these vessels per stem villus. The volumes and surface areas of intermediate and terminal villi were reduced (p < or = 0.001), especially in preterm growth-restricted cases, where a marked reduction in diastolic blood flow velocity was observed in the umbilical artery. CONCLUSIONS: Reduced villous development may contribute to abnormal umbilical artery blood flood flow, as assessed by Doppler ultrasonography, in some cases of intrauterine growth restriction.

Blood Flow Velocity↗

Use of Laplace transform analysis to describe the effect of placental embolisation on umbilical arterial Doppler waveforms in fetal sheep.

This is the first study to investigate changes in umbilical arterial Doppler shift waveforms caused by placental embolisation in fetal lambs described by a Laplace transform analysis method. The complete maximum velocity envelope of the waveform was quantified mathematically by the coefficients of the Laplace transform. The changes in the dominant coefficient were significantly correlated with changes in umbilico-placental vascular resistance. The Doppler shift waveforms reproduced those seen clinically in some growth-retarded pregnancies and were acquired in a clinically realistic manner. Increasing vascular resistance two fold in this experiment appeared to produce more consistent changes in the dominant coefficient of the Laplace transform than in the pulsatility index. Both analysis techniques correlated with umbilico-placental vascular resistance and these correlations were not significantly different from each other.

Animals↗

Vascular responsiveness in the unstressed borderline hypertensive rat.

This study compares vascular responses of unstressed borderline hypertensive rats (BHR) to age-matched Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Rings of thoracic aorta were mounted for isometric force determinations in tissue baths. Cumulative additions of phenylephrine (PE) or serotonin (5-HT) produced contractile responses in BHR aorta that were less than WKY but greater than SHR. Removing the endothelium increased force development to both agonists, with BHR showing the greatest increase. Based on EC50 determinations, no differences in PE sensitivity existed between groups, although in response to 5-HT, rings from SHR were significantly more sensitive than WKY. While the sensitivity of all rings increased with denuding, BHR showed a greater relative increase in sensitivity than WKY or SHR (intact EC50 divided by denuded EC50) to both PE and 5-HT. This suggests that there may be greater endothelium-derived relaxation in BHR than in WKY or SHR. In rings precontracted with 1 microM PE, the cumulative addition of acetylcholine resulted in greater relaxation in BHR than in SHR and WKY preparations. Thus, rings from unstressed BHR, which have only slightly higher blood pressures than WKY rats, demonstrate greater endothelium-mediated relaxation than WKY or SHR. Increased endothelium-derived relaxation may represent a possible mechanism for masking hypertension in BHR that is compromised as a result of exposure to a chronic stress paradigm.

Acetylcholine↗

Fetal blood transfusion.

The concept of transfusing the fetus in utero is simple, but its success demands an experienced, dedicated team, with excellent laboratory back-up. High-resolution ultrasound has enabled us to sample fetal blood. This allows immediate, precise assessment and rational treatment of the anemic fetus, with improved outcome for all such fetuses and, particularly, for the hydropic, moribund group. Fetal blood transfusion programs should be concentrated in regional perinatal centers.

Anemia↗

Prenatal diagnosis and management of anterior abdominal wall defects in the west of Scotland.

An attempt was made to identify all the cases of abdominal wall defects occurring in the West of Scotland over a 7-year period to determine the current incidence, prenatal diagnosis, management, and prognosis for fetuses and neonates with abdominal wall defects. Cases were identified because they presented either for prenatal diagnosis, or to the Department of Pathology following termination or spontaneous pregnancy loss, or as neonates to the Neonatal Surgical Department. The incidence of abdominal wall defects was found to be 1 in 2500 births. Exomphalos was diagnosed before birth in 66 per cent of cases, and in 30 per cent of cases it was associated with another major abnormality. There was a 20 per cent intact survival in the cases diagnosed prenatally who had no fetal anomaly and who opted to continue with the pregnancy. Gastroschisis was diagnosed before delivery in 70 per cent of cases, and in the group who continued with the pregnancy there was an intact survival of 77 per cent. Body stalk anomalies were all diagnosed prenatally and terminated. Maternal serum alpha-fetoprotein was elevated in 89 per cent of the cases with exomphalos and in 100 per cent of the cases with gastroschisis and body stalk anomalies in which it was tested.

Abdominal Muscles↗

Absent end-diastolic flow velocity waveforms in the umbilical artery--the subsequent pregnancy.

OBJECTIVE: Our purpose was to assess the recurrence risk, course, and outcome of subsequent pregnancies in women with absent umbilical end-diastolic velocity. STUDY DESIGN: Absent umbilical end-diastolic velocity was detected in 88 women. Sixteen of them were prospectively followed up in their 19 subsequent pregnancies. These pregnancies were compared with their index pregnancies. RESULTS: The index pregnancy was invariably complicated with a perinatal mortality of 56%, growth restriction in 94% (15/16), and prematurity in 100% (75% < 32 weeks' gestation). In contrast, the outcome of the subsequent pregnancies was much better, and 74% (14/19) were uncomplicated. No perinatal deaths occurred, and none were delivered before 32 weeks' gestation. Absent umbilical end-diastolic velocity recurred in only two pregnancies, both of which were complicated. Six women had autoantibodies; these accounted for 80% (4/5) of subsequent complicated pregnancies. CONCLUSION: After an index pregnancy with absent umbilical end-diastolic velocity, subsequent pregnancies had favorable outcomes. Recurrence of absent umbilical end-diastolic velocity was low. The absence of autoantibodies and normal Doppler studies were associated with improved outcome.

Adult↗

Experimentally induced changes in heart rate alter umbilicoplacental hemodynamics in fetal sheep.

In the anesthetized sheep fetus, we have accelerated heart rate by atrial pacing (n = 6) or caused decelerations by stimulating the vagus nerve (n = 7). Alterations in heart rate were linearly related to changes in the ratio of the diastolic minimum (D) to systolic maximum (S) of flow and velocity, and to changes in the flow pulsatility index in the umbilical artery. Decelerations slightly increased vascular resistance, and decreased blood flow and mean arterial pressure, but accelerations had no significant effect. The index of impedance was unaltered by either intervention. The major factor mediating the influence of heart rate on blood flow pulsatility in the umbilical artery was the aortic blood pressure pulsatility. An equation was derived to adjust flow D/S to a standardized heart rate. Results showed that heart rate correction can affect the interpretation of experimental data.

Animals↗

Isolation of acylcarnitines from urine: a comparison of methods and application to long-chain acyl-CoA dehydrogenase deficiency.

Carnitine esters from acetylcarnitine (C2 acyl chain) to octadecanoylcarnitine (C18 acyl chain) can be extracted from urine with recoveries of greater than 80%. However, to obtain such recoveries, it is important to choose the method of extraction appropriate to the acylcarnitines of interest. For acylcarnitines with acyl chain length C2 to C8 (acetylcarnitine to octanoylcarnitine), an ion-exchange procedure is recommended. Acylcarnitines with acyl chain length C8 to C12 (octanoylcarnitine to dodecanoylcarnitine) are best isolated from carefully acidified urine by solvent extraction with butan-1-ol. For long-chain acylcarnitines, C10 to C18 (decanoylcarnitine to octadecanoylcarnitine), solvent extraction of unacidified urine with hexan-2-ol is particularly simple and effective.

Acyl-CoA Dehydrogenase, Long-Chain↗

Cardiac electromechanical dissociation in the hypoxic fetal sheep may have clinical implications.

OBJECTIVES: Our purpose was to determine the sequence of fetal cardiac electrical and mechanical events associated with acute hypoxic acidemia and to correlate those events with terminal fetal heart rate patterns preceding fetal death. STUDY DESIGN: Eight acutely catheterized fetal sheep were rendered hypoxic by placental embolization with microspheres until fetal death occurred. The fetal electrocardiogram, Doppler cardiogram, left ventricular and aortic pressures, and fetal heart rate were continuously recorded. RESULTS: All eight fetuses showed a terminal bradycardia consisting of two phases: an initial phase of falling ventricular pressures, culminating in mechanical asystole, and a subsequent phase after asystole during which the electrocardiographic signal persisted for an average duration of 15.2 +/- 8.7 minutes (range 3.1 to 32.4) and triggered a Hewlett-Packard 8040A monitor to show a heart rate pattern. CONCLUSIONS: The phenomenon of cardiac electromechanical dissociation may be occurring during similar terminal bradycardias that are observed in human labor and explains the delivery of a fresh stillbirth in spite of the recording of an electrocardiographic signal from a scalp electrode.

Animals↗

Calcium mobilization and sensitivity in intact and triton skinned aorta from thyropathologic rats.

Calcium mobilization and sensitivity in aortic rings from hyperthyroid, hypothyroid, and euthyroid rats was examined. The magnitudes of contractions were measured in rings consecutively exposed to phenylephrine (1 microM) incubated in normal physiological saline (PSS), in calcium-free PSS and in normal PSS containing nifedipine (1 microM). By comparing the generated tension under these three conditions it was possible to estimate the contributions of calcium release from the sarcoplasmic reticulum (SR), of influx through voltage gated calcium channels (VGCC), and of influx through receptor operated calcium channels (ROCC). The comparison revealed no change in the contribution of SR calcium release in the three thyroid states, but showed increased VGCC influx and decreased ROCC influx in hyperthyroid rings. No changes were seen in the hypothyroid state. When rings were chemically "skinned" with triton X-100 and subsequently contracted with increasing concentrations of free calcium, dose response curves were not significantly different among rings from the three thyroid states. This suggests that changes in tension development in hyperthyroid aortic tissue may be due, in part, to alterations in membrane calcium influx rather than to SR calcium release or modified calcium activation of contractile elements.

Animals↗

Ultrasound detection of neural tube defects in patients with elevated maternal serum alpha-fetoprotein.

We conducted this study to determine the accuracy of ultrasound in the prenatal diagnosis of neural tube defects in women with elevated maternal serum alpha-fetoprotein (MSAFP). Among 905 pregnancies, 49 neural tube defects were correctly diagnosed by ultrasound alone; one was not. Ultrasound scanning had 98% sensitivity and 100% specificity for the detection of neural tube defects. The predictive value of a positive ultrasound diagnosis was 100% and of a negative ultrasound 99.9% for neural tube defects. Forty-three other structural abnormalities were also detected in patients with elevated MSAFP, including 19 abdominal wall defects, seven chromosomal abnormalities, five urinary tract abnormalities, one cardiac abnormality, and 11 others. Two chromosomal abnormalities were not detected. We suggest that ultrasound can be used reliably to detect neural tube defects, thereby avoiding the risks of amniocentesis.

Female↗

Prenatal diagnosis of an intra-abdominal sacrococcygeal teratoma.

The prenatal diagnosis of a presacral (type IV) sacrococcygeal teratoma (SCT) is described. The initial ultrasound appearance was suggestive of a lower urinary tract obstruction, but further ultrasonic examination and radiological imaging using contrast medium led to the diagnosis of SCT. This is the first prenatal diagnosis of a totally intra-abdominal SCT.

Adult↗

Hypoxic acidemia, hyperviscosity, and maternal hypertension do not affect the umbilical arterial velocity waveform in fetal sheep.

The effect of hypoxic acidemia, hyperviscosity, and maternal hypertension on the umbilical arterial velocity waveform was studied in 23 chronically catheterized fetal sheep. Fetal hypoxic acidemia induced by lowering the maternal inspired oxygen concentration (n = 7) caused no change in the ratio of systolic/diastolic blood velocity even when fetal arterial pH was as low as 6.8. Fetal blood hyperviscosity (n = 7) induced by exchange transfusion with packed maternal blood cells increased placental vascular resistance by greater than or equal to 50% but had no significant effect on the systolic/diastolic ratio. Similarly, maternal hypertension induced by intravenous infusion of angiotensin II to the ewe (n = 9) did not affect the systolic/diastolic ratio despite a 50% increase in maternal arterial blood pressure. We conclude that umbilical arterial velocity waveform abnormalities observed in growth-restricted human fetuses are probably not a direct result of fetal hypoxemia or hyperviscosity or maternal hypertension.

Acids↗

Site-dependent effects of increases in placental vascular resistance on the umbilical arterial velocity waveform in fetal sheep.

Placental vascular resistance was increased by embolization or by arterial vasoconstriction with angiotensin II and the effect on the flow and velocity waveforms in the umbilical artery was examined. Fetal sheep (n = 6) were studied under halothane anesthesia following the implantation of vascular catheters and an umbilical arterial electromagnetic flow probe. Blood flow and velocity (measured using Doppler ultrasound) gradually decreased during diastole and ultimately reversed in direction as cotyledon resistance was increased up to 14 fold. Cotyledon resistance was significantly correlated with the ratio of diastolic to systolic values (D/S ratio) of blood flow (r = -0.94) and velocity (r = -0.79). In contrast, increasing placental resistance up to 16 fold by constricting the umbilical arteries caused no significant change in the shape of the flow or velocity waveform.

Angiotensin II↗