Selective perfusion of coronary vasculature in preterm sheep: a methodological innovation undermined by unfavourable operation of the foramen ovale.

Antenatal cardiac intervention affords new prospects for hypoplastic left heart syndrome. Its success, however, may come not only from absence of impediments to blood flow but also from a sufficiently developed cardiac wall. Here, we examined the feasibility to perfuse selectively the fetal coronary circulation for treatment with growth promoting agents. Pregnant sheep (94-114 days gestation, term 145 days) were used. An aortic stop-flow procedure was developed for intracoronary access in the nonexposed fetus and human mesenchymal stem cells and their exosomes served as test agents. We found that aortic stop-flow ensures preferential distribution of fluorescent microspheres to the heart. However, intracoronary administration of stem cells or exosomes was detrimental, with fetal demise occurring around surgery or at variable intervals afterwards. Coincidentally, stop-flow caused by itself a marked rise of intraluminal pressure within the occluded aorta along with histological signs of coronary obstruction. We conclude that it is feasible to perfuse selectively the coronary circulation of the preterm fetus, but treatments are not compatible with survival of the animals. The cause for failure is found in the absence of hemodynamic compensation to stop-flow via a left-to-right shunt. This unexpected event is attributed to a largely membranous foramen ovale, characteristic of sheep, that collapses under pressure.

Foramen ovale blood flow and cardiac function after main pulmonary artery occlusion in fetal sheep.

NEW FINDINGS: What is the central question of this study? At near-term gestation, foramen ovale blood flow accounts for a significant proportion of fetal left ventricular output. Can the foramen ovale increase its volume blood flow when right ventricular afterload is increased by main pulmonary artery occlusion? What is the main finding and its importance? Foramen ovale volume blood flow increased during main pulmonary artery occlusion. However, this increase was attributable to an increase in fetal heart rate, because left ventricular stroke volume remained unchanged. These findings suggest that the foramen ovale has a limited capacity to increase its volume blood flow. ABSTRACT: The foramen ovale (FO) accounts for the majority of fetal left ventricular (LV) output. Increased right ventricular afterload can cause a redistribution of combined cardiac output between the ventricles. To understand the capability of the FO to increase its volume blood flow and thus LV output, we mechanically occluded the main pulmonary artery in seven chronically instrumented near-term sheep fetuses. We hypothesized that FO volume blood flow and LV output would increase during main pulmonary artery occlusion. Fetal cardiac function and haemodynamics were assessed by pulsed and tissue Doppler at baseline, 15 and 60 min after occlusion of the main pulmonary artery and 15 min after occlusion was released. Fetal ascending aorta and central venous pressures and blood gas values were monitored. Main pulmonary artery occlusion initially increased fetal heart rate (P < 0.05) from [mean (SD)] 158 (7) to 188 (23) beats min-1 and LV cardiac output (P < 0.0001) from 629 (198) to 776 (283) ml min-1 . Combined cardiac output fell (P < 0.0001) from 1524 (341) to 720 (273) ml min-1 . During main pulmonary artery occlusion, FO volume blood flow increased (P < 0.001) from 507 (181) to 776 (283) ml min-1 . This increase was related to fetal tachycardia, because LV stroke volume did not change. Fetal ascending aortic blood pressure remained stable. Central venous pressure was higher (P < 0.05) during the occlusion than after it was released. During the occlusion, fetal pH decreased and P C O 2 increased. Left ventricular systolic dysfunction developed while LV diastolic function was preserved. Right ventricular systolic and diastolic function deteriorated after the occlusion. In conclusion, the FO has a limited capacity to increase its volume blood flow at near-term gestation.

Fetal Physiology and the Transition to Extrauterine Life.

The physiology of the fetus is fundamentally different from the neonate, with both structural and functional distinctions. The fetus is well-adapted to the relatively hypoxemic intrauterine environment. The transition from intrauterine to extrauterine life requires rapid, complex, and well-orchestrated steps to ensure neonatal survival. This article explains the intrauterine physiology that allows the fetus to survive and then reviews the physiologic changes that occur during the transition to extrauterine life. Asphyxia fundamentally alters the physiology of transition and necessitates a thoughtful approach in the management of affected neonates.

Bi-level CPAP does not change central blood flow in preterm infants with respiratory distress syndrome.

BACKGROUND: Current literature provides limited data on the hemodynamic changes that may occur during bi-level continuous positive airway pressure (CPAP) support in preterm infants. However, the application of a positive end-expiratory pressure may be transmitted to the heart and the great vessels resulting in changes of central blood flow. OBJECTIVE: To assess changes in central blood flow in infants with respiratory distress syndrome (RDS) during bi-level CPAP support. DESIGN: A prospective study was performed in a cohort of 18 Very-Low-Birth-Weight Infants who were put on nasal CPAP support (4-5 cmH2O) because they developed RDS within the first 24-72 hours of life. Each subject was switched to bi-level CPAP support (Phigh 8 cmH2O, Plow 4-5 cmH2O, Thigh 0.5-0.6 seconds, 20 breaths/min) for an hour. An echocardiographic study and a capillary gas analysis were performed before and after the change of respiratory support. RESULTS: No differences between n-CPAP and bi-level CPAP in left ventricular output (LVO, 222.17 ± 81.4 vs 211.4 ± 75.3 ml/kg/min), right ventricular output (RVO, 287.8 ± 96 vs 283.4 ± 87.4 ml/kg/min) and superior vena cava flow (SVC, 135.38 ± 47.8 vs 137.48 ± 46.6 ml/kg/min) were observed. The hemodynamic characteristics of the ductus arteriosus were similar. A significant decrease in pCO2 levels after bi-level CPAP ventilation was observed; pCO2 variations did not correlate with modifications of central blood flow (LVO: ρ=0.11, p=0,657; RVO: ρ=-0.307, p=0.216; SVC: ρ=-0.13, p=0.197). CONCLUSIONS: Central blood flow doesn't change during bi-level CPAP support, which could become a hemodinamically safe tool for the treatment of RDS in preterm infants.

Progressive anatomical closure of foramen ovale in normal neonatal mouse hearts.

In the prenatal heart, right-to-left atrial shunting of blood through the foramen ovale is essential for proper circulation. After birth, as the pulmonary circulation is established, the foramen ovale functionally closes as a result of changes in the relative pressure of the two atrial chambers, ensuring the separation of oxygen depleted venous blood in the right atrium from the oxygenated blood entering the left atrium. Little is known regarding the process of anatomical closure of the foramen ovale in the postnatal heart. Genetically engineered mouse models are powerful tools to study heart development and to reveal mechanisms underlying cardiac anomalies, including defects in atrioventricular septation. Using three-dimensional reconstructions of serial sectioned hearts at early postnatal Days 2-7, we show a progressive reduction in the size of the interatrial communication throughout this period and complete closure by postnatal Day 7. Furthermore we demonstrate that fusion of the septum primum and septum secundum occurs between 4 weeks and 3 months of age. This study provides a standard timeline for morphological closure of the right-left atrial communication and fusion between the atrial septa in normal mouse hearts.

Value of scalp delayed rhythmic ictal transformation (DRIT) in presurgical assessment of temporal lobe epilepsy.

OBJECTIVES: To estimate the localising and lateralising value of delayed rhythmic ictal transformation (DRIT) on the scalp EEG during presurgical assessment for temporal lobe epilepsy. METHODS: Two hundred and eighty eight seizures recorded simultaneously with scalp and foramen ovale (FO) electrodes were studied retrospectively in 110 patients. DRIT was defined as sustained regular rhythmic waveforms seen on scalp recordings after scalp seizure onset. The incidence and laterality of scalp DRIT was evaluated by comparison to FO electrodes. RESULTS: Scalp DRIT was seen in 192 seizures, 65% of which showed focal mesial temporal onset (FMTO) recorded by FO electrodes. FMTO onset was seen in 73% of the 122 seizures showing unilateral scalp DRIT, in 32% of the 62 seizures showing bilateral asymmetrical scalp DRIT, and in 14% of the seven seizures showing bilateral symmetrical DRIT on the scalp. Among the 89 seizures showing unilateral scalp DRIT and FMTO, both were ipsilateral in 70 seizures (79%). Among the 38 seizures showing bilateral asymmetrical DRIT and FMTO, the largest amplitude of scalp DRIT was ipsilateral to the FO onset in 27 seizures (71%). CONCLUSION: Two thirds of seizures showed unilateral scalp DRIT, which had a lateralising value of up to 79%. SIGNIFICANCE: Scalp DRIT is a reliable marker to lateralise seizure focus in patients without a focal seizure onset on the scalp EEG.

Elevated left ventricular end-diastolic pressure favours closure of foramen ovale.

OBJECTIVE: It has been described that prevalence of patent foramen ovale (PFO) declines with age. Our hypothesis was that persistent high pressures in the left atria (LA), may facilitate closure of PFO and age would not play a role. METHODS AND RESULTS: The prevalence of PFO was studied in 201 consecutive patients with suspicion of cardioembolic stroke by contrast transoesophageal echocardiography. Left ventricular end-diastolic pressures (LVEDP) were estimated non-invasively by transthoracic echocardiography. Patients with normal diastolic function (DF) or with diastolic dysfunction (DD) stage I were considered as having normal LVEDP whereas patients with DD stage II or III as having elevated LVEDP. Prevalence of PFO was 42.8% and it was smaller in patients with elevated LVEDP than in patients with normal LVEDP (21.2% vs. 51.7%, P < 0.01). There was a smaller prevalence of PFO in patients with DD stage II than in patients with DD stage I or normal DF (25% vs. 51 and 54%, both P < 0.05). Size of the LA was larger in patients without PFO [34.73 ml/m2 (24.14-40.84ml/m2) vs. 27.86 ml/m2 (21.37-34.68 ml/m2), P < 0.05]. Mean age was 64.2 years (57.38-75.77) with no difference between patients with PFO and without PFO. In multivariate analysis Eustachian valve, atrial septal aneurysm, elevated LVEDP and large LA remained significantly associated (P < 0.05) with PFO. CONCLUSION: Elevated LVEDP and enlargement of LA are negatively associated with PFO. The higher the LVEDP, the lower the prevalence of PFO. Age is not associated with PFO.

Contribución diferencial de los estudios preoperatorios al diagnóstico en la cirugía de la epilepsia temporal / Differential contribution of preoperatory studies to diagnosis in temporal lobe epilepsy surgery

Introducción. Es preciso conocer el grado de confianza de las pruebas preoperatorias en epilepsia del lóbulo temporal (ELT). Objetivo. Analizar la importancia relativa de diferentes pruebas preoperatorias –videoelectroencefalograma (vEEG), electroencefalograma (EEG), tomografía computarizada por emisión de fotón único (SPECT) y resonancia magnética (RM)–, el grado de concordancia entre ellas y desarrollar un modelo probabilístico bayesiano para el diagnóstico. Pacientes y métodos. Se ha estudiado a 73 pacientes intervenidos de ELT, con un seguimiento postoperatorio mínimo de dos años. Para analizar la capacidad localizadora, se utilizan únicamente pacientes con un grado I de Engel durante todo el tiempo de seguimiento (n = 60). Resultados. Los porcentajes de los grados I, II, III y IV de Engel a los dos años fueron del 87,7, 8,2, 3,0 y 0%, respectivamente. La concordancia preoperatoria fue < 50% para tres pruebas y del 33% para las cuatro. Se encontraron estudios de RM normales en el 33,3% de los casos. Según el índice de localización, el orden es vEEG > RM > SPECT > EEG. La probabilidad condicional de obtener un grado I de Engel por prueba es: vEEG (0,950) > EEG (0,719) > SPECT (0,717) > RM (0,683). Para más de dos pruebas, la probabilidad condicional es ≤ 0,587 (vEEG + RM). La probabilidad de obtener un grado I de Engel a priori es vEEG (0,983) > RM (0,414) > EEG (0,285) > SPECT (0,209). El modelo bayesiano resulta ser muy sólido. Conclusiones. No siempre hay un alto grado de concordancia entre las pruebas, a pesar de lo cual puede obtenerse un buen resultado funcional. La prueba más eficaz es el vEEG (AU)

Introduction. It is necessary to know the degree of concordance of preoperative studies in temporal lobe epilepsy (TLE). Aim. To analyze the relative importance of different preoperative tests (vEEG, EEG, SPECT and MRI), the degree of agreement between them, and to develop a Bayesian probability model for diagnosis. Patients and methods. We analyzed 73 patients operated by TLE, with a minimum postoperative follow-up of two years. To analyze the localization capability of different test, we used only patients with an Engel’s grade I outcome during all the follow-up time (n = 60). Results. Engel’s grades percentages at 2 years were 87.7/8.2/3.0/0.0 (I/II/III/IV, respectively). The preoperative correlation was < 50% for three tests and 33% for the four. MRI studies were found normal in 33.3% of cases. According to the localization index, the arrange was vEEG > RM > SPECT > EEG. The conditional probability of correct localization for a test was vEEG (0.950) > EEG (0.719) > SPECT (0.717) > RM (0.683). Concordance for more than two tests, was ≤ 0.587 (vEEG + MRI). The probability of obtaining a priori correct localization was vEEG (0.983) > RM (0.414) > EEG (0.285) > SPECT (0.209). The Bayesian model is highly reliable. Conclusions. Probably it is not always possible to obtain a high degree of agreement among preoperative test, despite this, it is possible to obtain a good functional result. The most effective test is the vEEG (AU)