Acute fetal cardiovascular adaptation to artificial placenta in sheep model.

OBJECTIVE: To describe the acute cardiovascular adaptation of the fetus after connection to an artificial placenta (AP) in a sheep model, using ultrasound and invasive and non-invasive hemodynamic assessment. METHODS: This was an experimental study of 12 fetal sheep that were transferred to an AP system, consisting of a pumpless circuit with umbilical cord connection, at 109-117 days' gestation. The study was designed to collect in-utero and postcannulation measurements in all the animals. The first six consecutive fetuses were fitted with intravascular catheters and perivascular probes to obtain invasive physiological data, including arterial and venous intravascular pressures and perivascular blood flows, with measurements taken in utero and at 5 and 30 min after cannulation. These experiments were designed with a survival goal of 1-3 h. The second set of six fetuses were not fitted with catheters, and experiments were aimed at 3-24 h of survival. Echocardiographic assessment of cardiac anatomy and function, as well as measurements of blood flow and pre- and postmembrane pressures recorded by circuit sensors in the AP system, were available for most of the fetuses. These data were acquired in utero and at 30 and 180 min after cannulation. RESULTS: Compared with in-utero conditions, the pulsatility index at 30 and 180 min after connection to the AP system was reduced in the umbilical artery (median, 1.36 (interquartile range (IQR), 1.06-1.50) vs 0.38 (IQR, 0.31-0.50) vs 0.36 (IQR, 0.29-0.41); P < 0.001 for extreme timepoints) and the ductus venosus (median, 0.50 (IQR, 0.41-0.67) vs 0.29 (IQR, 0.22-0.33) vs 0.36 (IQR, 0.22-0.41); P = 0.011 for extreme timepoints), whereas umbilical venous peak velocity increased (median, 20 cm/s (IQR, 18-22 cm/s) vs 39 cm/s (IQR, 31-43 cm/s) vs 43 cm/s (IQR, 34-54 cm/s); P < 0.001 for extreme timepoints) and flow became more pulsatile. Intravascular monitoring showed that arterial and venous pressures increased transiently after connection, with median values for mean arterial pressure at baseline, 5 min and 30 min of 43 mmHg (IQR, 35-54 mmHg), 72 mmHg (IQR, 61-77 mmHg) and 58 mmHg (IQR, 50-64 mmHg), respectively (P = 0.02 for baseline vs 5 min). Echocardiography showed a similar transient elevation of fetal heart rate at 30 and 180 min after connection compared with in utero (median, 145 bpm (IQR, 142-156 bpm) vs 188 bpm (IQR, 171-209 bpm) vs 175 bpm (IQR, 165-190 bpm); P = 0.001 for extreme timepoints). Fetal cardiac structure and function were mainly preserved; median values for right fractional area change were 36% (IQR, 34-41%) in utero, 38% (IQR, 30-40%) at 30 min and 37% (IQR, 33-40%) at 180 min (P = 0.807 for extreme timepoints). CONCLUSIONS: Connection to an AP system resulted in a transient fetal hemodynamic response that tended to normalize over hours. In this short-term evaluation, cardiac structure and function were preserved. However, the system resulted in non-physiologically elevated venous pressure and pulsatile flow, which should be corrected to avoid later impairment of cardiac function. © 2023 International Society of Ultrasound in Obstetrics and Gynecology.

Estimated weight centile as a predictor of perinatal outcome in small-for-gestational-age pregnancies with normal fetal and maternal Doppler indices.

OBJECTIVE: To evaluate the risk of adverse perinatal outcome according to estimated fetal weight (EFW) in a cohort of term small-for-gestational-age (SGA) pregnancies with normal umbilical, fetal middle cerebral and maternal uterine artery Doppler indices. METHODS: A cohort of 132 term SGA fetuses with normal umbilical artery pulsatility index (PI), mean uterine artery PI and cerebroplacental ratio was compared to a control group of 132 appropriate-for-gestational-age babies, matched by gestational age at delivery. The capacity of the EFW percentile to predict Cesarean delivery, Cesarean delivery for non-reassuring fetal status (NRFS), neonatal acidosis and days of neonatal hospitalization was analyzed. RESULTS: As a whole, SGA fetuses with normal Doppler findings did not show a statistically significant difference for intrapartum Cesarean delivery (22.0 vs. 15.9%; P = 0.21) and neonatal acidosis (3.3 vs. 1.5%; P = 0.30), but had significantly higher risk for Cesarean delivery for NRFS (15.9 vs. 5.3%; P < 0.01) and longer neonatal hospitalization (1.39 vs. 0.87 days; P < 0.05) than did controls. SGA fetuses with EFW < 3(rd) centile had a significantly higher incidence of intrapartum Cesarean delivery (30.0 vs. 15.3%; P = 0.04), Cesarean delivery for NRFS (25.0 vs. 8.3%; P < 0.01) and longer neonatal hospitalization (2.0 vs. 0.9 days; P < 0.01) than those with EFW ≥ 3(rd) centile. SGA cases with EFW ≥ 3(rd) centile had perinatal outcomes similar to those of controls with normal EFW. CONCLUSION: Among SGA fetuses with normal placental and cerebral Doppler ultrasound findings, EFW < 3(rd) centile discriminates between those with a higher risk for adverse perinatal outcome and those with outcomes similar to those of normally grown fetuses.

Neurobehavioral outcomes in preterm, growth-restricted infants with and without prenatal advanced signs of brain-sparing.

OBJECTIVE: To evaluate the neurobehavioral outcomes of preterm infants with intrauterine growth restriction (IUGR), with and without prenatal advanced brain-sparing. METHODS: A cohort of IUGR infants (birth weight < 10(th) percentile with abnormal umbilical artery Doppler) born before 34 weeks of gestation was compared with a control group of appropriate-for-gestational age infants matched for gestational age at delivery. MCA pulsatility index was determined in all cases within 72 hours before delivery. Neonatal neurobehavior was evaluated at 40 weeks' ( ± 1) corrected age using the Neonatal Behavioral Assessment Scale. The effect of abnormal MCA pulsatility index (< 5(th) percentile) on each neurobehavioral area was adjusted for maternal smoking status and socioeconomic level, mode of delivery, gestational age at delivery, pre-eclampsia, newborn illness severity score and infant sex by multiple linear and logistic regression. RESULTS: A total of 126 preterm newborns (64 controls and 62 IUGR) were included. Among IUGR fetuses, the proportion of abnormal MCA Doppler parameters was 53%. Compared with appropriate-for-gestational age infants, newborns in the IUGR subgroup with abnormal MCA Doppler had significantly lower neurobehavioral scores in the areas of habituation, motor system, social-interactive and attention. Similarly, the proportion of infants with abnormal neurobehavioral scores was significantly higher in the IUGR subgroup with abnormal MCA Doppler parameters in the areas of habituation, social-interactive, motor system and attention. CONCLUSION: Abnormal MCA Doppler findings are predictive of neurobehavioral impairment among preterm newborns with IUGR, which suggests that this reflects an advanced stage of brain injury with a higher risk of abnormal neurological maturation.

Impact on fetal mortality and cardiovascular Doppler of selective ligature of uteroplacental vessels compared with undernutrition in a rabbit model of intrauterine growth restriction.

OBJECTIVES: To compare the impact on birth weight, mortality and fetal haemodynamic changes of selective ligature of uteroplacental vessels vs maternal undernutrition as experimental models of intrauterine growth restriction in the pregnant rabbit. METHODS: Three groups of NewZealand rabbit fetuses were compared: controls (n = 60), selective ligature of 40-50% of uteroplacental vessels (n = 38) and 70% diet restriction (n = 19), both starting at 25 days of gestation. Cardiovascular Doppler evaluation was performed before delivery in a subgroup of fetuses (15 controls and cases from surgical model and 10 fetuses from the undernutirtion model) before delivery including: umbilical artery pulsatility index (UAPI), middle cerebral artery pulsatility index (MCAPI), ductus venosus pulsatility index (DVPI), aortic isthmus pulsatility index (AoIPI), isovolumetric contraction time, ejection time, isovolumetric relaxation time (IRT), and myocardial performance index. Fetuses were delivered at 30 days of gestation by caesarean section and biometric measurements were recorded. RESULTS: The mortality rate was significantly higher in the surgical group (54.2%) than in the undernutrition (5%) and control (14.3%) groups (p < 0.001). Changes of biometrical measurements increased across experimental groups, being more pronounced in the surgical model. Ultrasound evaluation demonstrated linear trend for increased values in DVPI (p = 0.003) and AoIPI (p = 0.029), and IRT (p = 0.003) across study groups, but statistically significant changes were only observed in the surgical model. No significant differences were observed in the UAPI or MCAPI. CONCLUSIONS: While animal models fail to perfectly reproduce the human condition, selective ligature of uteroplacental vessels reproduces more closely cardiovascular features observed in human fetuses with intrauterine growth restriction when compared with undernutrition.

Neurodevelopmental outcome in 2-year-old infants who were small-for-gestational age term fetuses with cerebral blood flow redistribution.

OBJECTIVE: To assess the neurodevelopmental outcome at 2 years of age of children who had been small-for-gestational-age (SGA) term babies with cerebral blood flow redistribution. METHODS: Perinatal outcome was assessed in a cohort of 97 term singleton appropriate-for-gestational-age and 125 term singleton SGA fetuses with normal umbilical artery Doppler, stratified according to the presence of cerebral blood flow redistribution. Neurodevelopmental outcome was assessed prospectively at 2 years of age by means of the 24-month Age & Stage Questionnaire (ASQ). RESULTS: Of the 125 SGA fetuses, 25 had redistribution of the cerebral blood flow, and 100 did not. There were no significant differences in perinatal outcome between these two SGA groups. At 2 years of age, children who had been SGA fetuses with middle cerebral artery (MCA) pulsatility index (PI) < 5(th) centile had a higher incidence of suboptimal neurodevelopmental outcome compared with those with normal MCA-PI (52% vs. 31%; P = 0.049) and a lower mean centile in communication (53.1 vs. 67.4; P = 0.006) and problem-solving (39.7 vs. 47.4; P = 0.04) areas. CONCLUSION: SGA fetuses with cerebral blood flow redistribution have a higher risk of subtle neurodevelopmental deficits at 2 years of age. This challenges the concept that fetal cerebral redistribution is an entirely protective mechanism and suggests MCA-PI as a risk stratifying factor for adverse neurodevelopmental outcome.

Extraperitoneal laparoscopic para-aortic lymphadenectomy as a diagnostic procedure for lymph node recurrence of gynaecological cancers.

OBJECTIVE: The aim of this study was to evaluate the feasibility of extraperitoneal laparoscopic para-aortic lymphadenectomy for lymph node recurrence of gynecological cancers. METHODS: Seven patients underwent extraperitoneal laparoscopic para-aortic lymphadenectomies for suspected lymph node recurrence, detected by magnetic resonance image or CT scan. The suspicious nodes were removed through an extraperitoneal laparoscopic approach. RESULTS: The median age of patients was 51 years (range: 39-67). The median operating time was 207 min (range 120-300). There were no intraoperative or postoperative complications. The median nodal yield was 7.3 (range: 1-15). The median hospital stay was 2.5 days (range: 2-3). Histological examination revealed metastasis in 6 of the 7 patients. CONCLUSION: The extraperitoneal laparoscopic para-aortic lymphadenectomy for lymph node recurrence of gynecological cancers is a safe and feasible procedure which should be considered in the case of possible recurrence.

Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.

BACKGROUND: The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study. METHODS: Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes). RESULTS: Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients. CONCLUSIONS: Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.

Vasoactive hormones in uraemic patients with chronic hypotension.

BACKGROUND: We evaluated the possible role of an imbalance between vasoconstrictor and vasodilator hormones in the pathophysiology of chronic hypotension in uraemia. METHODS: Fourteen hypotensive haemodialysed patients, 14 normotensive haemodialysed patients, and 17 control subjects were included in this study. Plasma renin activity (PRA) and plasma levels of catecholamines, angiotensin II (AII), atrial natriuretic peptide (ANP), and arginine vasopressin (AVP) were measured. RESULTS: The mean time on haemodialysis (HD) was longer in hypotensive patients than in normotensive patients (P < 0.01). Catecholamine levels were higher in the whole group of HD patients than in controls (P < 0.01). Catecholamine levels were higher in hypotensive patients than in normotensive patients, but the differences reached significance only for adrenaline (P < 0.05). PRA and plasma AII levels were higher in hypotensive patients than in the other two groups (P < 0.05), while no differences were observed between normotensive patients and controls. Plasma ANP and AVP levels were higher in HD patients than in controls (P < 0.01), but there were no differences between hypotensive and normotensive patients. In HD patients, mean blood pressure inversely correlated with PRA (r = -0.59, P < 0.01) and plasma AII levels (r = -0.80, P < 0.01). CONCLUSIONS: Our results indicate that in HD patients with chronic hypotension there is an activation of the sympathetic and the renin-angiotensin systems. This activation is probably secondary in an attempt to compensate the vascular resistance to pressor stimuli reported in these patients.

[Autonomic dysfunction in chronic hypotension associated with uremia]. / Disfunción autonómica en la hipotensión crónica asociada a la uremia.

BACKGROUND: Chronic hypotension is a not uncommon complication among hemodialyzed patients which is responsible of an important morbidity. The autonomic nervous system (ANS) dysfunction seems to play a key role in the pathogenesis of chronic hypotension. METHODS: In order to study whether ANS dysfunction is responsible for chronic hypotension in hemodialyzed patients, the authors evaluated the integrity of the whole baroreflex arc by the Valsalva's manoeuver, of parasympathetic efferent pathway by the deep-breathing test and of sympathetic efferent pathway by the hand-grip test in 16 hemodialyzed patients with chronic hypotension, 17 normotensive hemodialyzed patients and 17 normal control subjects. Plasma catecholamine levels were also measured in these patients. RESULTS: In normotensive patients, Valsalva's manoeuver response (p < 0.005) and deep-breathing test response (p < 0.05) were lowered, while hand-grip test response was preserved. In chronic hypotensive patients, in addition to an impaired deep-breathing test (p < 0.05), a further reduced Valsalva's manoeuver response and a lower pressor response to hand-grip test were observed (p < 0.001). Catecholamine levels were higher in both groups of patients (p < 0.01) with respect to control subjects, specially in chronic hypotensive patients. CONCLUSIONS: In hemodialyzed patients (both normotensive and hypotensive) the whole baroreflex function and parasympathetic response are impaired. The lower pressor response to hand-grip test observed in hypotensive patients, in spite of the higher catecholamine levels, suggest that in these patients the cardiovascular dysfunction cannot be ascribed to a reduced sympathetic "outflow" but to a resistance of the target organs (heart and vessels) to the sympathetic stimulation.