Numerous studies have shown estrogen to be vasoactive in various circulations. Our objective was to determine the effect of estrogen on isolated bovine coronary arteries and the possible mechanism. Bovine coronary arteries, precontracted with thromboxane mimetic U46619 were given doses (0.01-30 microM) of 17B-estradiol in the presence and absence of endothelium and these inhibitors: 10 microM indomethacin (cyclooxygenase inhibitor), 10 microM methylene blue (inhibits soluble guanylate cyclase), 100 microM nitro-L-arginine (inhibits nitric oxide synthesis), 100 microM isobutylmethylxanthine (phosphodiesterase inhibitor) and 30 microM mifepristone (Ru38486 steroid receptor antagonist). Our results indicated that, estrogen, in the highest concentration used (30 microM), elicited an acute dose-dependent relaxation of bovine coronary arteries from 4%-68% (n = 15). No major difference in relaxation was observed between coronary arteries with or without endothelium, indicating that the mechanism was endothelium-independent. Indomethacin, nitro-L-arginine and methylene blue did not alter this relaxation, suggesting that relaxant prostaglandins, l-arginine products and cGMP are not involved (n = 11-16), isobutylmethylxanthine enhanced relaxation from 20%-40% (n = 15 p < 0.01), suggests a role for cAMP. Furthermore, mifepristone reduced the relaxation by more than 50% (n = 15 p < 0.05) consistent with the role for estrogen receptors. Based on our study, estrogen causes a dose-dependent relaxation of bovine coronary arteries that does not appear to utilize endothelium, prostaglandins, cGMP or arginine products, but may involve cAMP and estrogen receptors. This study may help justify treating myocardial ischemia with estrogen.

The last decade has seen tremendous growth and utilization of fetal echocardiography. In order to assess the indications and yield of fetal echocardiography at West Virginia University, all fetal echocardiograms performed during a seven-year period were reviewed. There were 931 fetal echocardiograms performed on 803 women during this time period and there was a large increase in referral rate as has been seen in other regions. The highest yield of abnormalities was seen in fetuses referred secondary to the finding of an abnormal fetal cardiac exam on routine screening ultrasound (55.6%), or fetal anomalies of other organs (8.2%). These two indications alone were responsible for 77.8% of identified cases of congenital heart disease by fetal echocardiography during this time period. The resultant findings highlight the need for thorough obstetrical screening ultrasound, including the four chamber view of the heart.

Pulmonary hypertension continues to be a major cause of morbidity and mortality, despite new treatments. Since inhaled nitric oxide has been reported to be effective in some cases, we investigated using nebulized nitroglycerine to treat pulmonary hypertension in children with congenital heart disease. Four children (ages 6-72 months) with severe pulmonary hypertension secondary to congenital heart disease (all with membranous ventricular septal defect, undergoing cardiac catheterization) were given 3 cc of nebulized normal saline over 10 min as placebo control, followed by nebulized nitroglycerine (20 micrograms/Kg in 3 cc normal saline). Normal saline administration did not elicit any change, but nitroglycerine administration resulted in the following changes (mean +/- SE, paired statistics): systolic pulmonary artery pressure from 68 +/- 8 to 53 +/- 6 at 10 min into treatment (P 0.006), mean pulmonary artery pressure 47 +/- 4 to 38 +/- 4 (P 0.005), heart rate 131 +/- 8 to 127 +/- 7 (P 0.13), systolic blood pressure 85 +/- 8 to 88 +/- 3 (P 0.7), mean blood pressure 59 +/- 6 to 63 +/- 4 (P 0.5). These results indicate that nebulized nitroglycerine may be an effective, easy to administer, inexpensive, and safe alternative for treatment of severe pulmonary hypertension in children with congenital heart disease, especially in areas where other treatments such as extracorporeal membrane oxygenation or inhaled nitric oxide are inaccessible.

In a study to compare the clinical diagnostic skills of academic general pediatricians and academic pediatric cardiologists in the evaluation of heart murmurs, a total of 128 patients (aged 1 month to 18 years) newly referred to a university pediatric cardiology clinic were evaluated by one of three general pediatricians and one of four pediatric cardiologists. The murmurs were clinically classified as innocent, pathologic, or possibly pathologic. The classification was revised after the review of electrocardiogram (EKG) and chest radiograph (CXR), if indicated. The definitive diagnosis was ascertained by echocardiography (94 normal, 34 abnormal). The general pediatricians identified as many pathologic heart murmurs as the pediatric cardiologists (27/34 vs. 29/34), with no difference in sensitivity, 79% vs. 85% (p=0.53). The similarity in sensitivity could be because the general pediatricians were more cautious in the classification of heart murmurs and had classified more innocent heart murmurs as pathologic than the pediatric cardiologists (13/39 vs. 3/23), 41% vs. 13% (p=0.02). The pediatric cardiologists correctly identified more innocent murmurs than general pediatricians (52/94 vs.72/94), with a better specificity, 55% vs. 76% (p=0.001); however, the accuracy of prediction of innocence was similar for both groups (52/59 vs. 72/77), 88% vs. 93% (p=0.36). The revision of diagnosis with review of EKG and CXR was more often misleading than helpful for either group. Academic general pediatricians would identify most of the pathologic murmurs and are no more likely than an academic pediatric cardiologist to misclassify a pathologic heart murmur as innocent. Clin Pediatr. 1999;38:511-518

A resurgence of acute rheumatic fever (ARF) was noted over the last 10 years in several areas of the United States. West Virginia was no exception with two reports appearing in the literature confirming an increased incidence in the 1980s among children and adults. The Pediatric Cardiology Division of West Virginia University Children's Hospital had 30 cases of ARF referred between 1980 and 1995, and surprisingly 27 of these cases had been diagnosed since 1986. This article describes our chart review of these 30 cases which studied epidemiological aspects, diagnostic criteria and regional differences by chi-square analysis. Other issues we present include "silent" mitral regurgitation and the unreliability of a history of a recent pharyngitis with or without appropriate antibiotic therapy while considering ARF in the differential diagnosis.

COMPARATIVE STUDY OF CLINICAL EVALUATION OF HEART MURMURS BY GENERAL PEDIATRICIANS AND PEDIATRIC CARDIOLOGISTS. † 818

INTRODUCTION:Antiarrhythmic medications are commonly used during pregnancy for treatment of maternal or fetal arrhythmias, but little is known about their effect on human placental vascular tone and, consequently, placental blood flow. The objective of this study was to evaluate the tone responses caused by antiarrhythmic medications in human placental vessels from normal term pregnancies in vitro.METHODS AND RESULTS:Isolated human placental arteries and veins from uncomplicated term pregnancies incubated in Krebs'-bicarbonate under 5% oxygen/5% carbon dioxide/balance nitrogen (PO2 35 to 38 torr) were exposed to cumulative doses of quinidine, procainamide, lidocaine, flecainide, propranolol, amiodarone, verapamil, digoxin, and adenosine after submaximal contraction with 5-hydroxytryptamine. The study was conducted both in the presence and absence of endothelium. The addition of the tested medications caused a significant, dose-dependent relaxation of human placental arteries and veins except for adenosine, which induced a sustained, dose-dependent contraction of human placental vessels regardless of the presence or absence of tone. Removal of the endothelium did not alter these responses.CONCLUSIONS:Based on these results, the medications tested should have no decremental effect on placental blood flow, with the possible exception of adenosine, which causes significant, dose-dependent contraction of human placental vessels in vitro. Should similar contraction be present in vivo, it may have an adverse effect on the fetus when administering adenosine to pregnant women at term or during labor.

We describe the use of two in vitro tests to characterize plasma antioxidant capacity at the time of cardiac bypass in operations for congenital heart disease in 30 patients aged 3 days to 16 years (average 4.4 +/- 0.9 years [standard error]). Bypass and crossclamp time, circuit volume, and type of operation were recorded for each patient. First, a test of plasma radical antioxidant power measured chain breaking (secondary) antioxidant capacity of plasma to prevent oxidation of linoleic acid in vitro. Second, overall ability of plasma to prevent lipid peroxidation was assessed by a classic test of plasma inhibition of malondialdehyde formation in a beef brain homogenate. Plasma total radical antioxidant power level at baseline was 0.74 +/- 0.03 mumol/ml plasma, which decreased to 0.15 +/- 0.05 mumol/ml plasma after bypass (p < 0.001) and 0.26 +/- 0.08 mumol/ml plasma with recovery (n = 18, p < 0.001). Analysis of variance of postbypass total radical antioxidant power value showed age (p = 0.0002, r = 0.63) and bypass time (p = 0.009, r = 0.4677) to be significant factors. Pump prime volume in milliliters per kilogram and preoperative hemoglobin value were not significant factors. Beef brain malondialdehyde formation in vitro was limited 92% +/- 3% by normal plasma before operation versus 53% +/- 5% after operation (p < 0.001) and 51% +/- 5% at recovery after arrival in the pediatric intensive care unit (p < 0.001). Analysis of variance of the changes from before to after operation showed age p = 0.0015, r = 0.55) and bypass time (p = 0.033, r = 0.39) to be significant factors. Thus antioxidant capacity of plasma is significantly diminished after cardiopulmonary bypass in children. Young patient age and long duration of cardiopulmonary bypass are identified as factors that correlate positively with depletion of antioxidant capacity with bypass.