Prostaglandin synthesis inhibition prevents placental dysfunction after fetal cardiac bypass.

Surgical therapy of certain congenital heart lesions in utero may have advantages over postnatal repair or palliation. For fetal heart operations to be done, it will be necessary to devise a method of fetal cardiac bypass. Previous studies in which standard cardiopulmonary bypass techniques were used have reported fetal death resulting from increased placental vascular resistance, which causes decreased placental blood flow and depressed respiratory gas exchange. The mechanism responsible for this increase in placental vascular resistance has remained unknown. In a series of 10 fetal cardiac bypass experiments we examined the role of prostaglandins as the mediators of this response. Observations were made during a 1-hour prebypass period, a 30-minute bypass period, and a 2-hour postbypass period. The cardiac bypass circuit consisted of a centrifugal pump, and bypass flows were adjusted to equal a normal fetal cardiac output of 400 ml/min/kg. In six of the experiments indomethacin (3 mg/100 ml) was added to the pump priming to block prostaglandin synthesis. By means of the microsphere technique, fetal cardiac output, placental blood flow, individual organ blood flow, and placental vascular resistance were determined at five times during the experiments: presternotomy, poststernotomy, during cardiac bypass, at 5 minutes after cessation of bypass, and 30 minutes after cessation of bypass. Fetal arterial blood gas measurements were made every 15 to 30 minutes. When indomethacin was used to inhibit prostaglandin synthesis, placental vascular resistance did not increase, placental blood flow did not decrease, and fetal blood gases remained at normal prebypass levels during and after fetal cardiac bypass. We propose that production of vasoactive prostaglandins is responsible for the increased placental vascular resistance and decreased placental blood flow observed after fetal cardiac bypass. An understanding of the mechanism responsible for the increased placental vascular resistance seen after fetal cardiac bypass will be an important first step before clinical application.

High-dose steroids prevent placental dysfunction after fetal cardiac bypass.

Surgical treatment of certain congenital heart lesions in utero may have a therapeutic advantage over postnatal repair or palliation. For fetal heart surgery to be possible, a method to support the fetal circulation is necessary. Early experimental attempts at fetal cardiac bypass were unsuccessful because of increased placental vascular resistance during and after fetal cardiac bypass, which led to decreased placental flow, fetal asphyxia, and death. Our laboratory has demonstrated that the administration of indomethacin (a cyclooxygenase inhibitor) during fetal cardiac bypass prevents this increase in placental vascular resistance during and after fetal cardiac bypass. The specific mechanism by which indomethacin achieves this effect is likely to be either by inhibiting the production of a placental vasoconstrictive prostaglandin or by diverting substrate from the cyclooxygenase pathway to the lipoxygenase pathway, thereby potentially increasing the production of a placental vasodilating leukotriene. To examine these potential mechanisms in more detail, we inhibited both prostaglandin and leukotriene synthesis at the phospholipase stage with high-dose steroids. Fourteen fetal lambs were used in the study. Six animals received indomethacin (3 mg/kg), four received high-dose steroids (Solu-Medrol 50 mg/kg), and four animals were used as controls. Observations were made during a 1-hour prebypass period, a 30-minute bypass period, and a 2-hour postbypass period. Placental blood flow and placental vascular resistance were calculated at four times during the experiments: before sternotomy; after sternotomy; during bypass at 30 minutes; and 30 minutes after cessation of bypass. Similar to indomethacin, high-dose steroid administration during fetal cardiac bypass prevents the rise in placental vascular resistance and preserves placental blood flow during and after fetal cardiac bypass. This study suggests that the production of a placental vasoconstrictive prostaglandin is responsible for the increase in placental vascular resistance and decrease in placental blood flow observed after fetal cardiac bypass.

Reversible pulmonary trunk banding with a balloon catheter: assessment of rapid pulmonary ventricular hypertrophy.

OBJECTIVE: We sought to assess the rapid hypertrophy of the right ventricle of young goats submitted to progressive pressure load by a balloon catheter. METHODS: The hearts of 6 young goats were assessed by means of echocardiography and cell morphology during and after right ventricular hypertrophy had been produced by a balloon catheter. Myocardial samples of the right ventricular outflow tract were harvested for microscopic studies. The external diameter of longitudinally sectioned myocytes was measured at the nucleus level. The volume density of mitochondria was also determined. A balloon catheter was then placed through the right ventricular outflow tract in the pulmonary trunk and progressively inflated every 2 days. Postoperative serial echocardiography was performed at intervals of 1 to 2 days. The animals were killed after 2 to 3 weeks of right ventricular training for morphologic analysis. RESULTS: Under optical microscopy, there was a 20.5% increase in the mean diameter of the myocyte of the trained right ventricle. However, under electron microscopy, there was no significant change in the mean volume density of mitochondria from the trained right ventricle. Serial echocardiography showed equalization of the ventricular thickness over a short interval of 6 to 10 days of progressive balloon inflation. CONCLUSIONS: The balloon catheter permits the manipulation of the pressure load over the right ventricle, causing rapid hypertrophy in a 6- to 10-day period. This study suggests that nonsurgical preparation of the "pulmonary ventricle" in patients with transposition of great arteries with intact ventricular septum beyond the neonatal period could probably be accomplished within a very few days.

Extracorporeal circulation in the isolated in situ lamb placenta: hemodynamic characteristics.

Decreased placental perfusion and respiratory gas exchange have been observed after experimental fetal cardiopulmonary bypass (CPB). To better characterize placental hemodynamics during CPB, seven isolated in situ lamb placentas were placed on a CPB circuit by use of umbilical arterial and venous cannulation. Measures were taken to simulate normal placental hemodynamics. Perfusion flow rates were varied from 15 to 300 ml.min-1.kg fetal wt-1 during normothermia and hypothermia. Placental vascular resistance (PVR) remained constant when perfusion pressure and flow were varied above 40 mmHg and 150 ml.min-1.kg-1, respectively. Below these values, PVR varied inversely. This increase in PVR was more marked when CPB was performed with hypothermia than with normothermia. The clinical implication is that decreased placental flow and pressure on CPB may lead to a vicious cycle, resulting in further impairment of placental perfusion and respiratory gas exchange. Hypothermia promotes this impairment.

Placental compliance during fetal extracorporeal circulation.

The fetus requires large amounts of volume when weaning from cardiac bypass. This suggests that placental vasculature can act as a large capacitor in the fetal circulation. To assess placental compliance of fetal lambs, seven isolated in situ lamb placentas were placed on extracorporeal circulation. Umbilical artery blood flow was varied from 0 to 350 ml. min(-1). kg fetal wt(-1). Because the extracorporeal circuit is a closed system, volume changes in the placenta induced by umbilical artery pressure changes were measured from reciprocal volume changes in the reservoir. There was a wide range of change in absolute volume of blood within the fetal placental compartment (216.4 +/- 29.3 ml). Placental compliance was linear over the entire range of pressure changes exerted on the placental vasculature (r(2) = 0.83, P = 0.0001). This indicates that the placenta is a unique and sensitive capacitor in the fetal circulation. This information is important clinically because it establishes that aggressive resuscitation of the fetus using volume may be necessary when weaning the fetus from cardiac bypass.

Cryosurgical ablation of fetal atrioventricular node: new model to treat fetal malignant tachyarrhythmias.

BACKGROUND: Sustained tachyarrhythmia resulting in fetal hydrops is often refractory to medical therapy. Fetal atrioventricular node ablation associated with epicardial fetal pacing has the potential to be an effective procedure for this morbid association. METHODS: To assess the feasibility of therapeutic fetal heart block, we developed a technique of intrauterine cryosurgical ablation of fetal atrioventricular node without the need for cardiac bypass in 8 fetal lambs. Complete heart block was obtained by applying the cryoprobe over the coronary sinus. Fetal pacing was then performed to allow fetal survival. RESULTS: Complete heart block was achieved in 100% of the fetal lambs. Postoperative evaluation revealed persistent atrioventricular block. The hearts were studied at different postoperative times. Morphologic evaluation of the area containing the cryosurgical lesion revealed varied extension of necrosis of the atrioventricular node and hemorrhage, with involvement of the His bundle and proximal right bundle branch. CONCLUSIONS: This procedure is technically feasible and offers an alternative approach to the treatment of drug-resistant, life-threatening fetal supraventricular tachyarrhythmias associated with hydrops fetalis.

Halothane as an anesthetic for fetal surgery.

Halothane has become the preferred anesthetic agent during fetal surgery because it can be administered via maternal inhalation and it improves surgical exposure by relaxing the uterus. However, the effects of halothane anesthesia on fetal cardiovascular homeostasis during fetal surgery have not been documented. In 10 pregnant ewes, inhalation halothane anesthesia was administered and their fetuses were instrumented for cardiovascular evaluation. During a 1-hour period we evaluated the acute effects of halothane anesthesia on fetal hemodynamics, arterial blood gases, cardiac output, placental blood flow, total vascular resistance, systemic vascular resistance, and placental vascular resistance. Fetal cardiac output and placental blood flow were determined by the radiolabelled microsphere technique and resistances were calculated using pressure and flow data. These findings were compared to both the results we obtained in 15 fetal sheep anesthetized with the maternal administration of intravenous ketamine, and to the accepted values found in nonanesthetized, chronically instrumented fetal sheep. Our findings indicate that with halothane anesthesia during fetal surgery fetal cardiac output and placental blood flow significantly decrease, and total vascular resistance increases. Placental vascular resistance increases out of proportion to systemic vascular resistance, resulting in the shunting of blood away from the placenta. The combination of decreased cardiac output and increased shunting of blood away from the placenta causes depressed respiratory gas exchange. These findings are not present with other anesthetic agents. Halothane has significant negative effects on both the fetal heart and the peripheral vasculature which disrupt fetal cardiovascular homeostasis. Halothane is a poor anesthetic during fetal intervention.

[Video-assisted surgery for closure of persistent ductus arteriosus. Study in sheep and initial clinical experience]. / Cirurgia vídeo-assistida para fechamento de canal arterial persistente. Estudo em carneiros e experiência clínica inicial.

PURPOSE: The aim of this study was to analyse the effectiveness of patent ductus arteriosus (PDA) closure by the video-assisted thoracic surgery (VATS). METHODS: The technique was utilized in 6 newborn lambs firstly. Three to four small incisions (3 to 10mm) were used in each animal to permit the introduction of lung retractors, video equipment, dissectors and clip appliers. The procedure was accompanied by video monitoring and after the dissection, the PDA was closed by 2 titanium clips. Seven days after, the animals were sacrificed and submitted to pathological study. Based on this initial experience seven patients (ages between 17 and 108 months) were operated on with this technique. RESULTS: In lambs, we have some difficulty to retract the lung. Despite this fact the closure of PDA was successful and proved by pathologic study. In children the dissection of PDA was easier due to manual ventilation. The interruption of PDA using the proposed method was obtained in 4 patients, those with good relation between ductus diameter and clip size and defined by echocardiography and angiographic studies. CONCLUSION: The use of VATS for interruption of PDA in both, experimental and initial clinical experiences, has showed to be an effective method.

Fetal heart block: a new experimental model to assess fetal pacing.

Epicardial fetal pacing via thoracotomy has the potential of being a safer and more reliable procedure to treat congenital complete heart block (CHB) associated with fetal hydrops refractory to medical therapy. To assess the acute electrophysiological characteristics of two ventricular epicardial leads, a new experimental model of fetal heart block induced by cryosurgical ablation of the AV node without the need for fetal cardiac bypass was performed in 12 pregnant ewes at 110-115 days gestation. A modified screw-in lead (1 1/2 turns) was used in six fetal lambs and a stitch-on lead in the other six lambs. CHB was achieved in 100% of the fetal lambs, with no ventricular escape rate noticed in any of the lambs. The acute stimulation thresholds were consistently low for both leads, with lower values for the screw-in lead at pulse duration below 0.9 msec (P < 0.03). Current measured at voltage threshold with pulse width below 0.5 msec was lower for the screw-in lead (P < 0.048). Stimulation resistance, measured during constant-voltage pacing, was not statistically different between the two leads (441.8 +/- 13.7 omega for the screw-in lead vs 480.2 +/- 59.2 omega for the stitch-on lead). No significant differences (P > 0.20) were found in R wave amplitude between the two electrodes. Slew rates were significantly higher in the screw-in group than in the stitch-on group (1.40 +/- 0.2 vs 0.62 +/- 0.2 V/sec, P = 0.04). This model of CHB is a simple and reproducible method to assess fetal pacing. We find the screw-in electrode to be a better option when fetal pacing is indicated.

Alteracoes macro e microscopicas dos rins de caes apos ligadura juxta-hilar da veia renal esquerda. / Macro and microscopic changes of kidneys of dogs after the juxta hilium ligation of the left renal vein

A ligadura da veia renal esquerda vem sendo assunto controvertido na literatura mundial. O estudo anatomo-patologico dos rins atingidos pela ligadura experimental foi o parametro utilizado pelos autores para maiores informacoes sobre o assunto.Foram utilizados doze caes para serem submetidos a ligadura justa-hilar da veia renal esquerda. Decorridos vinte e um dias, os caes foram submetidos a nefrectomia bilateral. As principais alteracoes macroscopicas foram diminuicao de peso e do volume, vascularizacao subcapsular bem desenvolvida e palidez difusa, especialmente cortical. A microscopia foram observados espessamento mesangial e consequente cilindruria, necrose papilar e fibrose intersticial, demosntrando um grave acometimento do rim cuja veia foi ligada. Analisando o material, conclui-se que as veias gonadal e supra-renal sao importantes vias de drenagem colateral para a preservacao da funcao renal