Peter M. Olley

E-type prostaglandins: a new emergency therapy for certain cyanotic congenital heart malformations.

Prostaglandin E2 (PGE2) has been used to maintain patency of the ductus arteriosus in four neonates with cyanotic congenital heart disease due to obstructive right heart malformations. PGE2 was infused prior to surgery, and in three patients, during surgery until a satisfactory aorto-pulmonary shunt was established. PGE2 produced consistently an immediate and persistent rise in arterial oxygen saturation, which could be ascribed to dilation of the ductus arteriosus. No major side effects occurred, except for pyrexia in two infants. All patients recovered well from surgery. We propose this treatment as preparation for surgery in any infant with congenital heart defects and ductus-dependent pulmonary blood flow. The same treatment may be useful preoperatively in patients with aortic interruption who also depend on continued patency of the ductus for blood supply to the lower half of the body.

Indomethacin and renal function in premature infants with persistent patent ductus arteriosus

Renal function during indomethacin treatment was studied in 12 premature infants with patent ductus arteriosus. Decreases in urinary flow rate, GFR, and CH2O by 56, 27, and 66%, respectively, occurred during Indo therapy. Urinary excretion rates of ions were also reduced: Na by 70%, Cl by 79%, K by 40%. These changes were accompanied by slight decreases in plasma sodium concentration and osmolality. Except for GFR and urinary Na and osmolality, all these functions returned to pretreatment values one to two weeks after stopping the drug.

Residual hypertension after coarctectomy in children

Coarctectomy in 190 children aged over 1 year to 15 years at operation produced a significant reduction in blood pressure for the group as a whole. Forty-nine patients (24 percent) remained hypertensive. Postoperative hypertension was unexplained in 29 (15 percent) of the 190 patients, and coarctation persisted or recurred in 20 (11 percent). For patients operated on between the ages of 4 and 15 years the earlier the age of operation, the greater the reduction in the blood pressure index: (measured blood pressure/normal mean systolic [or diastolic] blood pressure for age) X 100.

Abnormal endothelial factor VIII associated with pulmonary hypertension and congenital heart defects.

In patients with pulmonary hypertension associated with congenital heart defects, ultrastructural abnormalities are observed in endothelial cells, which suggest heightened metabolic function. If endothelial production of the von Willebrand factor (vWF) is increased, this may be associated with abnormal interactions with platelets leading to worsening of the pulmonary hypertension. We therefore evaluated vWF in 30 patients with pulmonary hypertension (25 with congenital heart defects) and in 30 individuals with normal pulmonary arterial pressure (12 with congenital heart defects). We measured the antigenic (vWF: Ag) and biologic (VWF: rist) activity of vWF in plasma and assessed endothelial vWF: Ag directly by an immunoperoxidase stain applied to lung biopsy tissue. Because of considerable variance and small size, the group of five patients with pulmonary hypertension and without congenital heart defects were excluded from statistical analyses. Patients with pulmonary hypertension and congenital heart defects had significant higher vWF: Ag levels than individuals with normal pulmonary arterial pressure without congenital heart defects (p less than .05), whereas values in those with normal pressure and congenital heart defects were intermediate. In lung biopsy tissue available from 29 patients in this study and from 11 others we previously reported, immunostain of pulmonary arterial endothelium for vWF was intense (suggesting increased production) in 29 of 32 with pulmonary hypertension and congenital heart defects and in only one of eight with normal pulmonary arterial pressure and congenital heart defects (p less than .01). Only three patients with congenital heart defects and pulmonary hypertension and increased vWF: Ag, however, had increased vWF: rist. Compatible with this discrepancy was a loss of vWF high-molecular weight forms as determined by both crossed immunoelectrophoresis and multimeric analysis. Our results suggest that increased vWF in most patients with congenital heart defects and pulmonary hypertension is associated with increased production of a biologically deficient molecule lacking high-molecular weight forms.

Lamb ductus arteriosus: effect of prostaglandin synthesis inhibitors on the muscle tone and the response to prostaglandin E2.

The prostaglandin synthesis inhibitors, indomethacin and eicosa-5,8,11, 14-tetraynoic acid (ETA), have been tested on the isolated lamb ductus arteriosus at low and high PO2 levels. Both compounds produced a gradual contraction of the hypoxic vessel, and at equal doses the effect of indomethacin was stronger. The maximal tension output of the hypoxic tissue under indomethacin was equal to that of the oxygen-contracted control. ETA- and indomethacin-treated preparations contracted further upon transfer from a low to a high oxygen environment, and the response under indomethacin exceeded a significantly control values. Control preparations were relaxed markedly by PGE2 in low oxygen but showed little or no response in high oxygen. In contrast, preparations pretreated with the inhibitors retained their sensitivity to PGE2 during exposure to high oxygen. The data are consistent with the idea that E-type prostaglandins play a role in the regulation of the intrinsic tone of the ductus arteriosus during foetal life. It is also suggested that the sensitivity of ductal muscle to E-type prostaglandins is controlled by the rate of endogenous prostaglandin formation.

The progressive nature of subaortic stenosis in congenital heart disease

Data derived from serial hemodynamic and angiocardiographic investigations on pediatric patients not subjected to intervening intracardiac operations support the view that subaortic stenosis in congenital heart disease tends to be a progressive disorder. Our data are obtained from two groups of patients. The first comprised 22 patients with discrete subaortic stenosis in relative isolation. The second was made up of 19 patients with the fibrous or fibromuscular forms of discrete subaortic stenosis associated with a perimembranous ventricular septal defect. The results from both groups support our initial contention. The progressive character of subaortic stenosis in these two situations illustrates the dynamic nature of congenital heart disease, and the tendency of a changing form and function.

Right ventricular volume determinations in 18 patients with pulmonary atresia and intact ventricular septum. Analysis of factors influencing right ventricular growth.

SUMMARYRight ventricular growth was assessed angiocardiographically in 18 patients with pulmonary atresia, intact ventricular septum, and hypoplastic and hypertensive right ventricle. A variety of surgical procedures were performed. In only 12 patients (66.7%) was right ventricular-pulmonary artery continuity achieved (group 1). Nine of these 12 patients persisted with systemic or suprasystemic right ventricular pressures. Among the six patients in whom right ventricular-pulmonary artery continuity was not achieved (group 2), all maintained suprasystemic right ventricular pressures.Right ventricular growth was assessed in groups 1 and 2. The patients were also subdivided according to the qualitative degree of tricuspid regurgitation as determined angiocardiographically on right ventricular cineangiocardiograms at the preoperative catheter study. Right ventricular growth to normal levels as evidenced by change in right ventricular end-diastolic volume was rarely observed in group 2 patients. Among the four patients with severe tricuspid regurgitation and a large tricuspid valve, right ventricular growth to normal levels was achieved whether they were in group 1 or group 2. Right ventricular growth is thus predicated on numerous morphologic factors in these patients. However, reconstitution of right ventricular-pulmonary artery continuity and a nonobstructive tricuspid valve are probably two of the more important factors.

Right ventricular ejection fraction and volumes after mustard repair: Correlation of two dimensional echocardiograms and cineangiograms

The right ventricular ejection fractions derived from two dimensional echocardiograms and cineangiograms were compared in 24 children. All patients (aged 2.1 to 16 years) had undergone Mustard repair for transposition of the great arteries 1 to 12 years earlier. The correlation of the two methods was excellent (r = 0.977), confirming the usefulness of echocardiography for deriving ejection fraction. The volume components of the ejection fraction were less well estimated from the echocardiograms, but the ratios of end-diastolic to end-systolic volumes estimated from each method were similar.

Bilateral ductus arteriosus (or remnant): An analysis of 27 patients

Bilateral ductus arteriosus (DA) was clinically recognized in 27 patients studied angiographically from 1963 through May 1983. Distal bilateral DA origin of non-confluent pulmonary arteries was identified in 15 patients, ectopic or distal ductal origin of 1 pulmonary artery in 9 patients (5 without evidence of intracardiac disease) and isolation of the left subclavian artery in 3 (all 3 of whom had a right aortic arch). Other conditions reported to be associated with bilateral DA include interruption of the aortic arch with isolation of a subclavian artery, aortic atresia with interruption of the aortic arch in which bilateral DA supports the entire systemic circulation, bilateral DA complicating forms of congenitally malformed hearts other than those just stated, and, rarely, bilateral DA in isolation. Understanding the symmetric or paired nature of the primitive aortic arch system in the developing human heart facilitates recognition of the patterns of fourth and sixth arch anomalies seen with bilateral DA.

Prostaglandin I2 is less relaxant than prostaglandin E2 on the lamb ductus arteriosus.

Prostaglandin (PG) I2 and its stable metabolite, 6-keto-PGF1alpha, were tested on the isolated ductus arteriosus from mature fetal lambs. PGI2 relaxed the ductus in high doses (threshold 10(-6)M) and its activity disappeared on standing at room temperature for 30 minutes. 6-keto-PGF1alpha was inactive at all doses. By contrast, PGE2 produced a dose-dependent relaxation over a range between 10(-10) and 10(-6)M. These findings confirm that PGE2 is the most potent ductal relaxant among the known derivatives of arachidonic acid. PGE2 probably maintains ductus patency in the fetus and, together with PGE1, remains the compound of choice in the management of newborns requiring a viable ductus for survival.