Fetal hemodynamic response to aortic valvuloplasty and postnatal outcome: a European multicenter study.

OBJECTIVE: Fetal aortic stenosis may progress to hypoplastic left heart syndrome. Fetal valvuloplasty (FV) has been proposed to improve left heart hemodynamics and maintain biventricular (BV) circulation. The aim of this study was to assess FV efficacy by comparing survival and postnatal circulation between fetuses that underwent FV and those that did not. METHODS: This was a retrospective multicenter study of fetuses with aortic stenosis that underwent FV between 2005 and 2012, compared with contemporaneously enrolled natural history (NH) cases sharing similar characteristics at presentation but not undergoing FV. Main outcome measures were overall survival, BV-circulation survival and survival after birth. Secondary outcomes were hemodynamic change and left heart growth. A propensity score model was created including 54/67 FV and 60/147 NH fetuses. Analyses were performed using logistic, Cox or linear regression models with inverse probability of treatment weighting (IPTW) restricted to fetuses with a propensity score of 0.14-0.9, to create a final cohort for analysis of 42 FV and 29 NH cases. RESULTS: FV was technically successful in 59/67 fetuses at a median age of 26 (21-34) weeks. There were 7/72 (10%) procedure-related losses, and 22/53 (42%) FV babies were delivered at < 37 weeks. IPTW demonstrated improved survival of liveborn infants following FV (hazard ratio, 0.38; 95% CI, 0.23-0.64; P = 0.0001), after adjusting for circulation and postnatal surgical center. Similar proportions had BV circulation (36% for the FV cohort and 38% for the NH cohort) and survival was similar between final circulations. Successful FV cases showed improved hemodynamic response and less deterioration of left heart growth compared with NH cases (P ≤ 0.01). CONCLUSIONS: We report improvements in fetal hemodynamics and preservation of left heart growth following successful FV compared with NH. While the proportion of those achieving a BV circulation outcome was similar in both cohorts, FV survivors showed improved survival independent of final circulation to 10 years' follow-up. However, FV is associated with a 10% procedure-related loss and increased prematurity compared with the NH cohort, and therefore the risk-to-benefit ratio remains uncertain. We recommend a carefully designed trial incorporating appropriate and integrated fetal and postnatal management strategies to account for center-specific practices, so that the benefits achieved by fetal therapy vs surgical strategy can be demonstrated clearly. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Natural history of 107 cases of fetal aortic stenosis from a European multicenter retrospective study.

OBJECTIVES: Fetal aortic valvuloplasty (FV) aims to prevent fetal aortic valve stenosis progressing into hypoplastic left heart syndrome (HLHS), which results in postnatal univentricular (UV) circulation. Despite increasing numbers of FVs performed worldwide, the natural history of the disease in fetal life remains poorly defined. The primary aim of this study was to describe the natural history of fetal aortic stenosis, and a secondary aim was to test previously published criteria designed to identify cases of emerging HLHS with the potential for a biventricular (BV) outcome after FV. METHODS: From a European multicenter retrospective study of 214 fetuses with aortic stenosis (2005-2012), 107 fetuses in ongoing pregnancies that did not undergo FV were included in this study and their natural history was reported. We examined longitudinal changes in Z-scores of aortic and mitral valve and left ventricular dimensions and documented direction of flow across the foramen ovale and aortic arch, and mitral valve inflow pattern and any gestational changes. Data were used to identify fetuses satisfying the Boston criteria for emerging HLHS and estimate the proportion of these that would have been ideal FV candidates. We applied the threshold score whereby a score of 1 was assigned to fetuses for each Z-score meeting the following criteria: left ventricular length and width > 0; mitral valve diameter > -2; aortic valve diameter > -3.5; and pressure gradient across either the mitral or aortic valve > 20 mmHg. We compared the predicted circulation with known survival and final postnatal circulation (BV, UV or conversion from BV to UV). RESULTS: Among the 107 ongoing pregnancies there were eight spontaneous fetal deaths and 99 livebirths. Five were lost to follow-up, five had comfort care and four had mild aortic stenosis not requiring intervention. There was intention-to-treat in these 85 newborns but five died prior to surgery, before circulation could be determined, and thus 80 underwent postnatal procedures with 44 BV, 29 UV and seven BV-to-UV circulatory outcomes. Of newborns with intention-to-treat, 69/85 (81%) survived ≥ 30 days. Survival at median 6 years was superior in cases with BV circulation (P = 0.041). Those with a postnatal UV circulation showed a trend towards smaller aortic valve diameters at first scan than did the BV cohort (P = 0.076), but aortic valve growth velocities were similar in both cohorts to term. In contrast, the mitral valve diameter was significantly smaller at first scan in those with postnatal UV outcomes (P = 0.004) and its growth velocity (P = 0.008), in common with the left ventricular inlet length (P = 0.004) and width (P = 0.002), were reduced significantly by term in fetuses with UV compared with BV outcome. Fetal data, recorded before 30 completed gestational weeks, from 70 treated neonates were evaluated to identify emerging HLHS. Forty-four had moderate or severe left ventricular depression and 38 of these had retrograde flow in the aortic arch and two had left-to-right flow at atrial level and reversed a-waves in the pulmonary veins. Thus 40 neonates met the criteria for emerging HLHS and BV circulation was documented in 13 (33%). Of these 40 cases, 12 (30%) had a threshold score of 4 or 5, of which five (42%) had BV circulation without fetal intervention. CONCLUSIONS: The natural history in our cohort of fetuses with aortic stenosis and known outcomes shows that a substantial proportion of fetuses meeting the criteria for emerging HLHS, with or without favorable selection criteria for FV, had a sustained BV circulation without fetal intervention. This indicates that further work is needed to refine the selection criteria to offer appropriate therapy to fetuses with aortic stenosis. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Fetal aortic valvuloplasty: investigating institutional bias in surgical decision-making.

OBJECTIVES: Fetal aortic valvuloplasty may prevent the progression of aortic stenosis to hypoplastic left heart syndrome and allow biventricular rather than univentricular postnatal treatment. This study aimed to investigate whether blinded simulation of a multidisciplinary team approach aids interpretation of multicenter data to uncover institutional bias in postnatal decision-making following fetal cardiac intervention for aortic stenosis. METHODS: The study included 109 cases of prenatally diagnosed aortic stenosis from 13 European countries, of which 32 had undergone fetal cardiac intervention. The multidisciplinary team, blinded to fetal cardiac intervention, institutional location and postnatal treatment, retrospectively assigned a surgical pathway (biventricular or univentricular) based on a review of recorded postnatal imaging and clinical characteristics. The team's decisions were the numerical consensus of silent voting, with case review when a decision was split. Funnel plots showing concordance between the multidisciplinary team and the local team's surgical choice (first pathway) and with outcome (final pathway) were created. RESULTS: In 105 cases the multidisciplinary team reached a consensus decision regarding the surgical pathway, with no decision in four cases because the available imaging records were inadequate. Blinded multidisciplinary team consensus for the first pathway matched the decision of the surgical center in 93/105 (89%) cases, with no difference in agreement between those that had undergone successful fetal cardiac intervention (n = 32) and no (n = 74) or unsuccessful (n = 3) valvuloplasty (no fetal cardiac intervention) (κ = 0.73 (95% CI, 0.38-1.00) vs 0.74 (95% CI, 0.51-0.96)). However, funnel plots comparing multidisciplinary team individual decisions with those of the local teams displayed more discordance (meaning biventricular-univentricular conversion) for the final surgical pathway following fetal cardiac intervention than they did for cases without such intervention (36/74 vs 34/130; P = 0.002), and identified one outlying center. CONCLUSIONS: The use of a blinded multidisciplinary team to simulate decision-making and presentation of data in funnel plots may assist in the interpretation of data submitted to multicenter studies and permit the identification of outliers for further investigation. In the case of aortic stenosis, a high level of agreement was observed between the multidisciplinary team and the surgical centers, but one outlying center was identified.

Total anomalous pulmonary venous connection: impact of prenatal diagnosis.

OBJECTIVES: To investigate whether prenatal screening is effective in the detection of total anomalous pulmonary venous connection (TAPVC) and to identify common prenatal features. METHODS: This was a retrospective collaborative study involving 19 pediatric cardiac centers in the UK, Ireland and Sweden. Cases with TAPVC born between January 1, 1998 and December 31, 2004, and prenatally diagnosed cases whose estimated dates of delivery were within this time frame, were identified. Cases with functionally univentricular circulation or atrial isomerism were excluded. All available data and stored images were reviewed. RESULTS: Four-hundred and twenty-four cases with TAPVC were identified prenatally or postnatally, of whom eight (1.9%) had a prenatal diagnosis of TAPVC. Median gestational age at fetal diagnosis was 26 + 6 (range, 22 + 4 to 32 + 0) weeks. Six further fetuses with TAPVC had an abnormality diagnosed on prenatal ultrasound, but not the TAPVC. This included other congenital heart defects (four cases) and isolated pleural effusion (two cases). Seventeen (4.0%) of the 422 liveborn infants had a first-degree relative with congenital heart disease; and six of 17 had a sibling with TAPVC. Two died in utero. Of the liveborn infants diagnosed prenatally with TAPVC, none required urgent intervention for pulmonary venous obstruction and all were alive and well at a median of 2.3 (range, 1.0-7.0) years after surgical repair. CONCLUSION: Prenatal diagnosis of TAPVC is infrequent using current screening methods. Where there is a family history of TAPVC, specialized fetal echocardiography at 20 and 28 weeks' gestation may be indicated.

Usefulness of colonoscopic examination with indigo carmine in diagnosing microscopic colitis.

Microscopic colitis, comprising collagenous colitis and lymphocytic colitis, is epitomized by chronic watery diarrhea, endoscopically normal colonic mucosa, and characteristic histopathological features. Reports on chromoendoscopic findings in microscopic colitis are scarce and in this paper we describe such findings. We have examined 13 patients with microscopic colitis by means of chromoendoscopy with indigo carmine 0.2 % - 0.5 %. In all 13 cases continuous mucosal changes were seen, with disappearance of innominate grooves or with irregularity of grooves. The segmental distribution of abnormal chromoendoscopic findings corresponded almost completely with the microscopic features. A diffuse mosaic pattern was found in five of 10 cases of collagenous colitis and in all three cases of lymphocytic colitis. Uneven surface was seen in four cases of collagenous colitis, one of collagenous colitis in remission, and one of lymphocytic colitis, and a nodular surface was recorded in five cases of collagenous colitis but in none of the lymphocytic colitis cases. If these findings can be reproduced in larger series of microscopic colitis cases, the need for biopsies as a diagnostic tool might be restricted to patients where chromoendoscopy shows clear mucosal changes, thereby saving costs and limiting possible complications associated with multiple biopsies.

A population-based investigation of the autoantibody profile in mothers of children with atrioventricular block.

The objective of the study was to investigate the antigen specificity and occurrence of individual autoantibodies in mothers of children diagnosed with atrioventricular (AV) block in a nation-wide setting. Patients with AV block detected before 15 years of age were identified using national quality registries as well as a network of pediatric and adult cardiologists and rheumatologists at the six university hospitals in Sweden. Patients with gross heart malformations, surgically or infectiously induced blocks were excluded. Blood samples were obtained from the mothers and maternal autoantibody profile, including the occurrence of antibodies against Ro52, Ro60, La, SmB, SmD, RNP-70k, RNP-A, RNP-C, CENP-C, Scl-70, Jo-1, ribosomal RNP and histones was investigated in 193 mothers of children with AV block by immunoblotting and ELISA. Autoantibody reactivity was detected in 48% (93/193) of the mothers of children with AV block. In autoantibody-positive mothers, the vast majority, 95% (88/93), had antibodies against Ro52, while 63% (59/93) had autoantibodies to Ro60 and 58% (54/93) had autoantibodies to La. In addition, 13% (12/93) of the autoantibody-positive mothers had antibodies to other investigated antigens besides Ro52, Ro60 and La, and of these anti-histone antibodies were most commonly represented, detected in 8% (7/93) of the mothers. In conclusion, this Swedish population-based study confirms that maternal autoantibodies may associate with heart block in the child. Further, our data demonstrate a dominant role of Ro52 antibodies in association with AV block.

Z-scores of the fetal aortic isthmus and duct: an aid to assessing arch hypoplasia.

OBJECTIVE: Prenatal diagnosis of isolated coarctation of the aorta suffers from high false positive and false negative rates. The aim of our study was to develop Z-scores for the aortic isthmus in normal fetuses as a reference for fetuses with suspected coarctation. METHODS: The aortic isthmal diameter, immediately proximal to the insertion of the arterial duct, was measured prospectively in the transverse (three vessel and trachea) and sagittal views in 221 normal fetuses at 18 to 37 weeks' gestation. The ductal diameter was measured immediately before it entered the descending aorta in the same view. All measurements were repeated three times by a single investigator and averaged. A second investigator re-measured the images of 50 cases to assess interobserver variability. Z-scores were created relating isthmal and ductal diameters to femur length and gestational age. The ratio between the isthmal and ductal diameters was calculated. RESULTS: The formula used to calculate Z-scores for the three diameters was: [ln(measured isthmal diameter) - (m ln(femur length or gestational age) + c)]/root MSE, where c is the intercept, m is a multiplier and MSE is the mean squared error. The ratio between isthmal and ductal diameters was close to a constant value of 1 (95% CI 0.97-1.01), regardless of the value of femur length or gestational age. CONCLUSION: We have defined Z-scores for the fetal aortic isthmus and arterial duct measured in the three vessels and trachea view and for the isthmus in the sagittal plane. In suspected coarctation, these Z-scores and the isthmal to ductal ratio may help in longitudinal assessment of the aortic arch and aid in the prenatal diagnosis of coarctation.

Quality of life in children with hypoplastic left heart syndrome.

AIM: To measure quality of life in children with hypoplastic left heart syndrome and their families. METHODS: A questionnaire exploring socioeconomic status, structure and function of networks and psychological well-being was completed by the families of all 18 patients older than 2 years (age range 2.7-10.6). The results were compared with those of 180 healthy Swedish children matched for age and sex. RESULTS: There were no significant differences between the groups in any of the aspects of socioeconomic status. Study group parents had not more available time for their child (p < 0.05) and more separations/divorces (p < 0.01). The patients had lower self-esteem (p < 0.05), more psychosomatic symptoms (p < 0.01) [corrected] and lower peer acceptance (p < 0.01) than control children. CONCLUSION: With regard to psychological well-being, quality of life was significantly lower in children with hypoplastic left heart syndrome than in healthy controls.

Bubble contrast echocardiography in detecting pulmonary arteriovenous malformations after modified Fontan operations.

The development of pulmonary arteriovenous malformations is a well-known complication after Fontan operations, and may result in significant morbidity due to increasing arterial desaturation. We compared the use of bubble contrast echocardiography and pulmonary angiography in detecting such malformations. We also examined which anatomical and haemodynamic variables were associated with their development. Our study includes 20 patients who had undergone modified Fontan procedures, 10 with atriopulmonary and 10 with total cavopulmonary connections, in Gothenburg between 1980 and 1991. All patients underwent cardiac catheterisation and pulmonary angiography. Bubble contrast echocardiography was performed at the same time, with injection of agitated polygelin colloid solution (Haemaccel, Hoechst) into the right and left pulmonary arteries, respectively. Transoesophageal echocardiography was used to detect the appearance of bubble contrast in the pulmonary venous atrium. The aim was also to evaluate the role of hepatic venous blood. Of the 20 patients, 9 (45%) had a positive contrast echocardiography study, compared with only 2 (10%) detected by pulmonary angiography. Patients with positive contrast echocardiography had a significantly lower arterial oxygen saturation than those with negative studies, both at rest (88% vs 95%, p < 0.01) and during exercise testing (78% vs 89%, p = 0.01). Bubble contrast echocardiography is much more sensitive in detecting pulmonary arteriovenous malformations than pulmonary angiography. By injecting echo contrast into the right and left pulmonary arteries, the method can be made highly selective. Pulmonary arteriovenous malformations develop much more frequently in patients with the Fontan circulation than previously reported.

Transient reduction of human left ventricular mass in carnitine depletion induced by antibiotics containing pivalic acid.

OBJECTIVE: To study the effect of induced carnitine depletion on myocardial structure and function. SUBJECTS AND DESIGN: 7 healthy adult volunteers given 1200 mg pivmecillinam per day for 7-8 weeks were studied by echocardiography before and after 7-8 weeks of treatment and a 15 months follow up after the treatment period. SETTING: Teaching hospital. MAIN OUTCOME MEASURES: Carnitine concentration in serum, urine, and muscle and echocardiographic measurements. RESULTS: After 7-8 weeks of treatment the median free serum carnitine concentration was reduced to 7% and the median total muscle carnitine concentration to 46% of the pretreatment levels. The median diastolic interventricular septum thickness decreased by 14% (mean 26%, P = 0.028) and the median left ventricular mass by 10% (mean 20%, P = 0.018). Fifteen months later these dimensions had increased but not completely returned to pretreatment values. CONCLUSIONS: Extended treatment with pivalic acid containing antibiotics causes carnitine depletion which may lead to changes in cardiac structure.

Transventricular dilation for critical aortic stenosis in neonates.

Critical aortic stenosis (CAOS) is not compatible with life when the ductus arteriosus closes. We have treated 11 consecutive cases with isolated CAOS. Symptom presentation was in the early neonatal period and diagnosis was made noninvasively at a mean age of 4 days. All were operated on with transventricular dilation (TVD) at a mean age of 4.7 days. There was no early mortality. There were two late deaths due to fibroelastosis. Both had the smallest aortic anulus diameter (5 mm). Two other patients had aortic root replacement, one at the age of 6.5 weeks due to intractable heart failure, and the other at the age of 3 months due to increasing gradient. In these two cases elective surgery was made possible by a successful TVD in the early neonatal period. TVD in this material was not associated with any early mortality, which makes this procedure a good alternative in the treatment of CAOS.

The influence of epidural blockade and pethidine administered during delivery on neonatal myocardial performance.

The aim of the present study was to investigate whether obstetric analgesia with an epidural blockade (Marcaine, bupivacaine hydrochloride, 141.5 +/- 56.8 mg) and pethidine (95.0 +/- 30.7 mg) influenced neonatal myocardial function following vaginal delivery. Left ventricular output and other left ventricular function indices were measured 5.6 +/- 4.3 h postpartum with Doppler and M-mode echocardiography in a group of healthy, full-term, appropriate-for-gestational-age infants (n = 10) whose mothers had received both bupivacaine and pethidine during delivery, and in a similar group of newborn infants (n = 10) whose mothers had received only nitrous oxide/oxygen analgesia. In 7 of the 10 infants in each groups, a second assessment of myocardial function was performed 21.7 +/- 4.6 h post partum. There were no significant differences in any of the variables used to assess left ventricular function at either of the measurement points between the group of infants whose mothers had received bupivacaine/pethidine during delivery, and the group of infants whose mothers had received nitrous oxide/oxygen analgesia only.

Effect of subclavian flap angioplasty on growth and circulation of the left front leg in pigs.

The effect of subclavian flap angioplasty on the growth of the left front limb and on its collateral circulation was studied in 11 pigs. The left subclavian artery and its first branch, the costocervical trunk, were divided while the remaining three branches--the deep cervical, the vertebral and the internal thoracic artery--were preserved. Postoperative angiographies (5 pigs) showed that the blood supply to the left front limb was maintained through these three branches, which acted as collaterals, supplying blood in retrograde fashion. The left vertebral artery was seen to be the predominant collateral already on postoperative day 1. Four months later the diameter of the left vertebral artery had increased more than that of the contralateral (right) vertebral artery. Eight months postoperatively the size of both front legs (6 pigs) was the same. No signs of cerebral disturbance were seen. The clinical implications of the findings are discussed.

Effects of left-to-right ductus shunting on left ventricular output and cerebral blood flow velocity in 3-day-old preterm infants with and without severe lung disease.

The effects of early left-to-right ductus shunting on left ventricular output (LVO) and cerebral blood flow velocity (CBV) were investigated in 3-day-old preterm infants by means of two-dimensional Doppler and M-mode echocardiography. Nineteen infants required mechanical ventilation because of severe lung disease (group A), and 19 had mild or no lung disease (group B). Six infants in each group had predetermined Doppler and M-mode criteria of a hemodynamically significant left-to-right ductus shunt (hsPDA). In group A the LVO was similar in infants with and without hsPDA, but those with hsPDA had lower mean arterial pressure (p = 0.006) and lower mean systolic-diastolic CBV (p = 0.001) than those without hsPDA. In group B the presence of hsPDA was associated with a higher LVO (p = 0.002), whereas neither mean arterial pressure nor mean systolic-diastolic CBV differed significantly in infants with and without hsPDA. In infants without hsPDA, those in group A had higher LVO (p = 0.012), lower mean arterial pressure (p = 0.003), and lower estimated systemic vascular resistance (p = 0.004) than those in group B. These results indicate that severely ill preterm infants receiving mechanical ventilation are less able than spontaneously breathing infants to defend systemic pressures and cerebral perfusion through an increase of LVO when a large ductus shunt develops. Possible reasons include an elevated baseline LVO, caused by systemic vasodilation, and hence a low preload reserve.

Prevention of symptomatic patent ductus arteriosus with a single dose of indomethacin.

To determine the efficacy of indomethacin to prevent the occurrence of symptomatic patent ductus arteriosus (PDA), a randomized clinical trial was conducted involving 32 preterm infants weighing 750 to 1500 g at birth who had hyaline membrane disease. By random assignment, 15 infants were given a single dose of indomethacin, 0.2 mg/kg intravenously, 24 hours after birth. Seventeen infants composed a control group for which indomethacin was reserved as treatment for symptomatic PDA. Birth weight, gestational age, male/female ratio, black/white ratio, and severity of disease were similar for both groups. Only one of the 14 survivors who received prophylactic indomethacin had symptomatic PDA, compared with nine of the 16 survivors in the control group (P = 0.007). There was no difference between the groups in development of bronchopulmonary dysplasia, duration of time endotracheal intubation, was required, duration in oxygen, duration to reach full feedings and regain birth weight, and duration of hospital stay. There was no difference between the two groups in incidence of intraventricular hemorrhage, and none developed necrotizing enterocolitis. These results indicate that the use of prophylactic indomethacin is beneficial in prevention of symptomatic PDA; the lack of differences in pulmonary sequelae or other complications may have been related to a population sample size not large enough to impart sufficient statistical power.

Prediction of symptomatic patent ductus arteriosus in preterm infants using Doppler and M-mode echocardiography.

To investigate whether the development of symptomatic patent ductus arteriosus could be predicted, 26 preterm infants dependent on mechanical ventilation were examined daily with Doppler and M-mode echocardiography until 3 days after birth. The presence or absence of a hemodynamically significant ductus shunt, as judged from echocardiographic criteria, was tested for predictive power in terms of sensitivity, specificity and total error rate. Out of the 26 infants 13 developed symptomatic patent ductus arteriosus at a median age of 5 days (range 2-8). These 13 infants developed echocardiographic evidence of a large shunt at a median age of 2 days (range 1-3). The sensitivity of prediction was 18, 46 and 100% at 1, 2 and 3 days after birth. The specificity was 80, 92 and 85% and the total error rate was 52, 32 and 8%. Thus, accurate prediction was possible 3 days after birth.

Neonatal surgery for coarctation of the aorta. The Gothenburg experience.

Thirty-four neonates (weights 0.97-4.47 kg) were operated on for coarctation of the aorta. They included five premature infants with birth weight less than or equal to 2.1 kg. All 34 were symptomatic, 31 severely so. Coarctation was "simple" in 12 cases and "complex" in 22; 12 with ventricular septal defect and 10 with more complex malformations. The mean age at operation was 11 days. Subclavian flap aortoplasty was used in 27 cases, a lusoric artery in two, and combined end-to-end anastomosis and flap repair in five. The main pulmonary artery was banded in 13 of the 22 complex coarctation syndromes. Absorbable suture was used in the last 22 cases. There was one early postoperative death. Serious ischaemic complications (bowel or limb gangrene) arose in four patients who were in severe heart failure preoperatively. During follow-up averaging 1.9 years there were two recurrences of coarctation. Resection with end-to-end anastomosis combined with subclavian flap aortoplasty when there is bulging ductal tissue or long, narrow isthmus and use of absorbable vascular suture may further lower the incidence of recurrent coarctation.

Doppler determination of cardiac output in infants and children: comparison with simultaneous thermodilution.

Ten children, aged six weeks to 13 years, without intracardiac shunts or lesions that could cause turbulent flow in the ascending aorta or aortic regurgitation, underwent cardiac catheterization, including cardiac output measurements by thermodilution. Simultaneously with each of six consecutive thermodilution injections, mean and maximal blood velocities in the ascending aorta were measured by pulsed Doppler echocardiography from the suprasternal notch. Aortic root and aortic orifice diameters were measured with M-mode and cross-sectional echocardiography. One patient had to be excluded from the analysis because of inadequate Doppler recordings. The best agreement with the results of the thermodilution was observed when internal systolic aortic root diameter was combined with mean velocity (r = 0.97, y = 0.90x + 0.28, SEE = 0.31 liters/min). When cardiac output was normalized for body size, there was still a good correlation between the results of these two methods.

Effect of epidermal growth factor on lung liquid secretion in fetal sheep.

Fetal lung liquid secretion depends on active transport of chloride ions. Chloride secretion in the stomach is inhibited by epidermal growth factor (EGF). For this reason, the effect of EGF on lung liquid secretion was measured using the impermeant-tracer technique in chronically-prepared fetal sheep. Infusion of EGF over 4 h resulted in decreased lung liquid secretion (from 4.2 +/- 0.6 to 1.7 +/- 0.8 ml/h, P = 0.02) and significant dose related tachycardia. During the infusion, plasma epinephrine levels increased from 27 +/- 5 to 67 +/- 13 pg/ml (P = 0.05) and norepinephrine levels increased from 257 +/- 31 to 544 +/- 69 pg/ml (P = 0.01). Since it is known that beta-adrenergic agonists inhibit lung liquid secretion, subsequent studies were performed with beta-adrenergic blockade using propranolol. Infusion of EGF and propranolol resulted in a significant decrease in lung liquid secretion (from 8.9 +/- 2.1 to 3.0 +/- 1.1 ml/h, P = 0.03). Infusion of propranolol alone had no demonstrable effect on lung liquid secretion. It is concluded that acute EGF infusion increases heart rate and stimulates catecholamine secretion in fetal sheep. EGF also inhibits lung liquid secretion, an effect which appears to be independent of a possible indirect catecholamine effect.