use of prostaglandin e1 in infants with d-transposition of the great arteries and intact ventricular...

PEDlATRiC CARDIOLOGY

Use of Prostaglandin El in Infants With d-Transposition of

The Great Arteries and intact Ventricular Septum

PETER LANG, MD MICHAEL D. FREED, MD FREDERICK 2. BIERMAN, MD WILLIAM I. NORWOOD, Jr., MD, FACC

ALEXANDER S. NADAS, MD, FACC

Boston, Massachusetts

Prostaglandin El was used to treat five infants with d4ransposition of the great arteries and intact ventricular septum who had persistent severe hypoxemia after the creation of an interatrial communication. Three infants had a dramatic improvement in systemic arterial oxygen saturation associated with dilation of the ductus arteriosus; in two of the three cases urgent surgery was avoided. Two infants had no clinical evidence of increased ductal shunting and no improvement in oxygen saturation. A trial of prostaglandin El is recommended for treatment of severe hypoxemia in infants with d-transposition of the great arteries with intact ventricular septum if the presence of a large atrial septal defect is established.

From the Departments of Cardiology and Cardio- vascular Surgery, the Children’s Hospital Medical Center and the Departments of Pediatrics and Surgery, Harvard Medical School, Boston, Mas- sachusetts. This study was supported in part by Grant HL05855 from the National Institutes of Health, Bethesda, Maryland. Manuscript received December 12, 1978; revised manuscript received February 13. 1979, accepted February 14, 1979.

This newborn was the 2,950 g product of an uncomplicated term pregnancy. Increasing cyanosis was observed during the 1st day of life, and she was transferred to Children’s Hospital Medical Center, Boston, at age 24 hours. Physical examination revealed a markedly cyanotic infant in no distress. The pulse rate was 160/min, the respiratory rate 64/min and the systolic blood pressure 65 mm Hg in the right arm and 70 mm Hg in the right leg. The lungs were clear to auscultation. There was a quiet precordium. Both the first and second heart sounds were single. There was a grade 2/6 short systolic ejection murmur at the upper left sternal border. There was no hepatomegaly, and peripheral pulses were normal. A chest X-ray film showed a normal heart size and normal pulmonary vascularity. An electrocardiogram showed right axis deviation and right ventricular hypertrophy. Arterial oxygen tension (POs) was 26 torr in room air with no change in 100 percent oxygen.

Emergency cardiac catheterization revealed d-transposition of the great arteries with an intact ventricular septum, a patent foramen ovale, a small patent ductus arteriosus and a right aortic arch. Systolic pressure in the left ventricle was approximately two thirds of simultaneous systemic systolic pressure and,

Address for reprints: Peter Lang, MD, Depart- l Prostaglandin Et is a phase II drug undergoing clinical trials and has been made available ment of Cardiology, Children’s Hospital Medical to US by The Upjohn Company, Kalamazoo, Michigan. We thank them for their assistance Center, 300 Longwood Avenue, Boston, Massa- with our ongoing work. Inquiries concerning the availability of prostaglandin E, should be chusetts 02115. directed to Sharon Reischer, Medical Research Coordinator, The Upjohn Company.

Prostaglandin El* has been shown to be a potent dilator of the ductus arteriosus-” It has been used to dilate the ductus arteriosus and thereby increase pulmonary blood flow and systemic arterial oxygen saturation in infants with pulmonary stenosis or atresia in whom adequate pulmonary blood flow is dependent on patency of the ductus.4m8 It has also been shown to be effective in infants with interruption of the aortic arch whose systemic blood flow is dependent on patency of the ductus arteriosus.g,‘O Two reports 8~11 have suggested the beneficial effect of prostaglandin Ei infusion in infants with d-transposition of the great arteries.

We have recently used prostaglandin El in five newborns with d- transposition of the great arteries and intact ventricular septum. Each infant had low systemic arterial oxygen saturation after creation of an interatrial communication. In three of the infants, prostaglandin Ei infusion through an umbilical arterial catheter or a peripheral venous line resulted in improvement in systemic arterial oxygen saturation.

Case Reports

Case 1

76 Jufy 1979 The American Journal of CARDIOLOGY Volume 44

although the pulmonary artery was not entered, there was no angiographic evidence of pulmonary stenosis. A balloon atria1 septostomy was performed with a no. 5F Edwards septostomy catheter (Edwards Laboratories, Santa Ana, California) filled to 4 cc, which resulted in an insignificant increase in PO2 from 24 to 27 torr. Four hours after catheterization, the PO2 remained less than 30 torr.

Prostaglandin El was infused at a dose of 0.1 pglkg per min. through an umbilical arterial catheter positioned at the level of the ductus arteriosus. There was an immediate increase in t,he intensity of the murmur to grade 4/6 and an increase in PO:! to 38 torr in room air. Prostaglandin El was continued for 80 hours with maintenance of PO:! at 35 to 45 torr. After discontinuation of prostaglandin El, PO2 was maintained at more than 30 torr. There was no murmur of a patent ductus arteriosus. The patient was discharged; she thrived at home.

A repeat cardiac catheterization at age 7 months revealed d-transposition of the great arteries with intact ventricular septum, no patent ductus arteriosus, a right aortic arch and left ventricular pressure one third of systemic systolic pressure. There was good interatrial mixing, and systemic oxygen saturation was 73 percent. At age 7 l/Z months she underwent corrective surgery with the placement of an intraatrial baffle employing Brom’s modification of the Senning procedure.12 At age 15 months, the patient is asymptomatic and receiving no medication.

Case 2

This newborn was the 3,260 g product of an uncomplicated term pregnancy. Increasing cyanosis was observed during the first day of life, and she was transferred to Children’s Hospital Medical Center, Boston, at 36 hours of age. Physical examination revealed a cyanotic infant in no distress. The pulse rate was 160/min, the respiratory rate 60/min and the systolic blood pressure 60 mm Hg in the right arm. The lungs were clear to auscultation. There was a quiet precordium. The first heart sound was normal; the second sound was single. No murmur was noted. There was no hepatomegaly, and the peripheral pulses were normal. A chest X-ray film revealed mild cardiomegaly and slightly increased pulmonary vascularity. An electrocardiogram indicated right axis deviation and right

TABLE I

Case 2. Cardiac Catheterization Data

Balloon Atrial Septostomy With Before After PGE,

02gy % 1

24 30 38

R”v” 43: 61 87

Ao

:c 9”: 9”: 9’9’ 98 92 97

Pressure (mm Hg)

:v” (7) (4) (7)

6317 Ao 63140 76f50 78148 LA (8) LV

(4) (7) 4916 4818 5417

Figures in parentheses are mean pressures. Ao = descending thoracic aorta; LA = left atrium; LV = left ventricle;

O2 sat (oxygen saturation at room air)(FIO* = 0.21); PGE, = during infusion of prostaglandin El at 0.1 pglkg per min; RA = right atrium; RV = right ventricle; SVC = superior vena cava.

ventricular hypertrophy. A two dimensional echocardiogram performed from the subxiphoid position revealed d-transposition of the great arteries with intact ventricular septum, a patent foramen ovale and a small patent ductus arteriosus. Arterial PO2 was 25 torr in room air.

Emergency cardiac catheterization revealed d-transposition of the great arteries with intact ventricular septum, a patent foramen ovale, a small patent ductus arteriosus, and left ventricular pressure two thirds of systemic systolic pressure with no angiographic evidence of pulmonary stenosis (Table I). A balloon atria1 septostomy was performed with a no. 5F Edwards septostomy catheter filled to 4 cc, which resulted in an increase in PO:! from 25 to 30 torr. A repeat two dimensional echocardiogram revealed a moderate-sized interatrial communication with a flail septum primum (Fig. 1).

PROSTAGLANDIN E, IN TRANSPOSITION OF GREAT ARTERIES-LANG ET AL.

FIGURE 1. Case 2. Two dimensional echocardiograms of the atrial anatomy, before (top) and after (bottom) balloon atrial septostomy. Ant-inf = anterior-inferior; Arrowhead = septum primum within foramen ovale; C = catheter within right atrium: Double arrows = interatrial communication; LA = left atrium; It = left: post-sup = posterior-superior: RA = right atrium; rt = right.

July 1979 The American Journal of CARDIOLOGY Volume 44 77


When prostaglandin El was infused at a dose of 0.1 I.cg/kg per min through an umbilical arterial catheter positioned at the level of the ductus arteriosus, PO2 increased to 40 torr. A repeat aortogram showed marked dilation of the patent ductus arteriosus with increased shunting from the aorta to the pulmonary artery. The prostaglandin El infusion was continued for 24 hours with maintenance of POs at more than 40 torr in 30 percent oxygen. After discontinuation of prostaglandin El, PO2 decreased to 24 torr. Reinfusion of prostaglandin Er at 0.005 pg/kg per min for 72 hours maintained POs at more than 35 torr. Once again, infusion of prostaglandin Er was discontinued and PO2 decreased to 28 torr. Prostaglandin Er was infused at 0.002 pug/kg per min for 144 hours with PO2 at more than 40 torr. POs decreased to 30 torr after discontinuation of prostaglandin El.

At age 22 days (10 days after prostaglandin Er was discontinued), the infant underwent a Senning procedure and ligation of the ductus arteriosus under deep hypothermic circulatory arrest. Her postoperative course was uncomplicated. At age 5 months, she is asymptomatic and receiving no medication.

Case 3

This newborn was the 3,175 g product of a term pregnancy complicated by maternal hypertension. The child was transferred to Children’s Hospital Medical Center, Boston, at age 12 hours because of cyanosis and respiratory distress. Physical examination revealed a markedly cyanotic infant who was intubated and in moderate respiratory distress. The pulse rate was 130/min and the systolic blood pressure 60 mm Hg in the right arm and 80 mm Hg in the left leg. The lungs were clear to auscultation. There was a quiet precordium. The first heart sound was normal; the second sound was single. There was a grade 2/6 short systolic ejection murmur at the upper left sternal border. There was no hepatomegaly, and peripheral pulses were normal. A chest X-ray film revealed mild cardiomegaly and slightly increased pulmonary vascularity. An electrocardiogram revealed right axis deviation and right ventricular hypertrophy. Arterial POs was 24 torr in room air and 30 torr in 100 percent oxygen.

Emergency cardiac catheterization revealed d-transposition of the great arteries with intact ventricular septum, a patent foramen ovale, a small patent ductus arteriosus, and left ventricular pressure equal to systemic systolic pressure with no angiographic evidence of pulmonary stenosis. A balloon atria1 septostomy was performed with a no. 5F Edwards septostomy catheter filled to 4 cc, which resulted in an increase in PO2 from 20 to 40 torr. A two dimensional echocardiogram revealed a large interatrial communication. There was a gradual decrease in PO:! to 20 torr over the next 48 hours.

Prostaglandin El was infused through a peripheral vein at a dose of 0.1 pg/kg per min. There was an immediate increase in PO2 (Fig. 2). Prostaglandin El was continued for 4 days; POs remained more than 40 torr. On discontinuation of the infusion, PO2 decreased to 27 torr. With reinstitution of prostaglandin El, POs again increased to 40 torr. Prosta- glandin Er infusion was discontinued at age 10 days because of a large local accumulation of interstitial fluid secondary to intravenous line infiltration. On this occasion, POs decreased over a period of 48 hours to 30 torr. Prostaglandin Er was reinfused; PO2 increased to more than 40 torr. Over the first 2 weeks of life, the patient gained 400 g and became markedly edematous. A third attempt to wean the patient from prostaglandin El was unsuccessful.

At age 15 days, a Senning procedure and ligation of the patent ductus arteriosus were performed using deep hypo- thermia and circulatory arrest. At operation, marked edema and friability of all tissues were noted. After operation, the infant had low cardiac output, pulmonary insufficiency and renal failure. He died on the 5th postoperative day. Post- mortem examination of the heart revealed d-transposition of the great arteries with intact ventricular septum, adequate- sized and unobstructed pulmonary venous and systemic venous atria1 chambers and a small communication across the interatrial baffle.

Case 4

This newborn was the 3,130 g product of an uncomplicated term pregnancy. At age 18 hours she underwent cardiac catheterization because of severe hypoxemia. This revealed

po;! IN RELATION TO PGE, (CASE31

BAS AGE (days)

To SURGERY

FIGURE 2. Case 3. Response of arterial oxygen tension (~0~) in relation to the prostaglandin (PG)E, infusion (shaded areas). BAS = balloon atrial sep- tosomy

78 July 1979 The American Journal of CARDlOLGGY Volume 44

d-transposition of the great arteries with intact ventricular septum, a patent foramen ovale, a small patent ductus arteriosus and left ventricular pressure two thirds of systemic pressure. A balloon atria1 septostomy, performed with the balloon filled to 3 cc, resulted in an increase in PO2 from 20 to 30 torr. During the next 4 days, POz ranged from 12 to 31 torr. At age 5 days, the infant was transferred to Children’s Hospital Medical Center, Boston. Arterial PO:! was 21 in 100 percent oxygen. A two dimensional echocardiogram revealed d-transposition of the great arteries with intact ventricular septum, a small interatrial communication partially occluded by septum primum, no left ventricular outflow tract obstruction and no patent ductus arteriosus.

The patient was taken to the operating room and a Bla- lock-Hanlon atria1 septectomy was performed. Immediately postoperatively, PO2 increased to 44 torr (in 100 percent oxygen). Six hours postoperatively, however, it decreased to less than 20 torr (in 100 percent oxygen). Prostsglandin El was infused at 0.1 pg/kg per min for 45 minutes with no significant effect on POa. No murmurs were heard, and the arterial pulse pressure was unchanged. Over the next 3 days, PO* slowly increased to more than 30 torr (in 30 percent oxygen). The infant was discharged from the hospital; it is planned that she will undergo elective surgery at age 6 months.

Case 5 This newborn was the 3,940 g product of an uncomplicated

term pregnancy. At age 15 hours he underwent cardiac catheterization because of severe hypoxemia. This revealed d- transposition of the great arteries with intact ventricular septum, a patent foramen ovale and left ventricular pressure equal to systemic pressure with no angiographic evidence of pulmonary stenosis. No patent ductus arteriosus was seen in a left ventricular cineangiogram. A balloon atria1 septostomy, performed with the balloon filled to 2.5 cc, resulted in an increase in arterial oxygen saturation from 31 to 56 percent. At age 3 days, the infant was transferred to Children’s Hospital Medical Center, Boston because of recurrent hypoxemia. Arterial POZ was 20 torr in room air. A two dimensional echocardiogram revealed d-transposition of the great arteries with intact ventricular septum, a moderate-sized interatrial communication with a flail septum primum, no left ventricular outflow tract obstruction and no patent ductus arteriosus.

At age 5 days, because of persistent hypoxemia (PO:! less than 20 torr), prostaglandin El was infused at a dose of 0.1 pg/kg per min through an umbilical arterial catheter. There was no change in POa, and no murmur appeared. Arterial blood pressure decreased from 101/67 to 87/55 mm Hg and the prostaglandin Et infusion was discontinued after 1 hour. Over the next 5 days, PO2 remained at less than 25 torr. A repeat echocardiogram showed a small interatrial communication. At age 11 days, a Blalock-Hanlon atria1 septectomy was performed. Postoperatively, PO2 increased to more than 30 torr in room air. Elective surgical repair is planned for the infant at age 6 months.

Discussion

D-transposition of the great arteries with intact ventricular septum is one of the most common forms of cyanotic congenital heart disease presenting in the newborn period. ia Current recommendations for treatment are the creation of an interatrial communication by balloon atria1 septostomy at the time of pre- sentation, followed by a definitive surgical procedure sometime before age 1 year. With such an approach, the l-year survival rate approaches 85 percent.14 At Chil-

dren’s Hospital Medical Center, Boston, we have used this approach with highly favorable results.15 However, we have found that in a small group of infants hypoxemia persists despite an apparently good balloon atria1 septostomy. In this situation surgical septectomy usu- ally does not relieve the hypoxemia. When these infants are subjected to definitive surgical procedures in the newborn period their mortality is greater than that of infants and children undergoing elective surgery at an older age.‘” Two recent developments have altered the approach to these patients at our institution: the ability to evaluate the adequacy of the balloon at.rial septostomy and the use of prostaglandin El.

Two dimensional echocardiography to evaluate the adequacy of balloon atria1 septostomy: When performed from the subxiphoid position, two dimensional echocardiography allows reliable visualization of the entire interatrial septum.‘” If hypoxemia persists after the performance of a balloon atria1 septostomy, and if an echocardiographic image of the atria1 septum reveals a small communication, then a surgical septectomy would be expected to improve the patient’s con- dition. However, if hypoxemia persists after the performance of a balloon atria1 septostomy and if an echocardiographic image of the atria1 septum reveals a moderate to large interatrial communication, then the hypoxemia cannot be attributed to an inadequate defect, and palliative surgery is unlikely to benefit the patient.

Use of prostaglandin El in cyanotic congenital heart disease: This treatment has had dramatic beneficial effects in neonates whose pulmonary blood flow is dependent on patency of the ductus arteriosus. In these neonates, prostaglandin Ei causes dilatation of the ductus with an increase in the total pulmonary blood flow and, therefore, in the systemic arterial oxygen saturation. It seemed reasonable that patients with d-transposition of the great arteries and intact ventricular septum might similarly benefit from the use of prostaglandin El. Dilatation of the ductus arteriosus would presumably result in increased pulmonary blood flow. Mair and Ritter’; suggested that increased pulmonary blood flow will result in increased intercirculatory mixing at the atria1 level and an improvement in systemic arterial oxygen tension. If an adequate inter- atria1 communication exists, and if the total right to left and left to right shunts must be equal in transposition,‘” then an obligatory left to right shunt at the level of the patent ductus arteriosus (aorta to pulmonary artery because systemic vascular resistance is greater than pulmonary vascular resistance) would result in an obligatory left atria1 to right atria1 shunt. This combi- nation of increased pulmonary blood flow and higher right atria1 oxygen saturation would result in a higher systemic oxygen tension (Fig. 3).

An alternative explanation for improved systemic arterial oxygen saturation during prostaglandin El infusion is that prostaglandin El reduces pulmonary vascular resistance and, thus, increases pulmonary blood flow. It is well established that prostaglandin El is a potent dilator of the pulmonary vascular bed in

PROSTAGLANDIN Et IN TRANSPOSITION OF GREAT ARTERIES-LANG ET AL.

July 1979 The American Journal of CARDIOLOGY Volume 44 79


FIGURE 3. Diagrams showing intercirculatory mixing in d-transposition of the great arteries with intact ventricular septum. Left, with only an interatrial communication, there is equal right to left and left to right shunting at the atrial level. Right, with an interatrial communication, a patent ductus arteriosus and pulmonary vascular resistance less than systemic vascular resistance, there is aorta to pulmonary artery shunting and an obligatory equal amount of left atrial to right atrial shunting. Ao = aorta; LA = left atrium; LV = left ventricle; PA = pulmonary artery; PDA = patent ductus arteriosus; PV = pulmonary veins; RA = right atrium; RV = right ventricle; SV = systemic veins.

rabbits, dogs, swine and lambs’s as well as in healthy adult men.ig In d-transposition of the great arteries with intact ventricular septum, a lesser pulmonary vascular resistance might decrease left ventricular afterload and might also result in an increase in pulmonary blood flow.

Evaluation of treatment in the five cases: The reason for improvement after prostaglandin El infusion in our patients cannot be determined with certainty. In Case 1, it seems reasonable to assume that the initial improvement was based on ductal dilatation with increased total pulmonary blood flow and a secondary increase in interatrial mixing. After discontinuation of prostaglandin El, there was no longer evidence of ductal shunting, but satisfactory arterial oxygen saturation persisted. Such a result is compatible with decreasing pulmonary resistance and increasing pulmonary blood flow during the 1st week of life. Repeat catheterization at age 7 months confirmed the closure of the ductus arteriosus and normal pulmonary resistance. The prostaglandin Ei thus supported the patient over sev- eral critical days, obviating the need for early surgical intervention.

The effect of prostaglandin El in Case 2 seems to have been similar to that in Case 1. The initial improvement in systemic arterial oxygen saturation was associated with ductal dilation and increased aorta to pulmonary artery shunting (shown angiographically). However, on the three occasions that the prostaglandin El was discontinued, systemic arterial oxygen saturation decreased to preinfusion levels. We do not know whether the failure to maintain adequate oxygenation resulted from a persistent elevation of pulmonary vascular resistance or was due solely to poor intercirculatory mixing at the atria1 level in the absence of a significant ductal shunt. Although this infant had surgical

80 July 1979 The American Journal of CARDIOLOGY Volume 44

repair during the initial hospitalization, the procedure was carried out at age 22 days rather than at age 36 hours.

The third case is more difficult to evaluate. The response to prostaglandin Ei was unequivocal on four occasions (Fig. 2) but there was never clinical evidence of a large ductal shunt. Although it is reasonable to postulate that the improvement in systemic arterial oxygen saturation was due solely to a decrease in pulmonary vascular resistance, significant ductal flow re- mains the most likely explanation. This patient required discontinuation of prostaglandin Ei support and surgical intervention at age 15 days because we feared prostaglandin Ei had led to severe fluid retention. Al- though the surgical repair was satisfactory, the patient died 5 days later. This patient received prostaglandin Ei for a longer period (13 days) than any other patient in our experience, and the fluid retention and tissue friability may be related to duration of treatment or to the total dose of prostaglandin El. However, other infants have been reported 11s20 to have taken prostaglandin Ei for considerably longer periods of time without significant ill effects. In addition, no similar episode was observed among the first 270 neonates in the United States treated with prostaglandin El (per- sonal communication, Sharon L. Reischer, The Upjohn Company).

Patients 4 and 5 showed no improvement in systemic arterial oxygen saturation while they were receiving prostaglandin El. There were no clinical manifestations of ductal shunting. Both infants were transferred to our institution after initial management at other hospitals. In one, the ductus arteriosus was not seen at the first catheterization and, in the other, it may have closed in the 4 days between the catheterization and the administration of prostaglandin El.

The status of the interatrial communication in Pa- tient 5 merits additional comment. On initial two dimensional echocardiographic evaluation at our institution, the interatrial communication appeared to be of adequate size. Accordingly, when hypoxemia persisted, the infant was given a trial of prostaglandin El. There was no increase in oxygen saturation and no evidence of ductal shunting. When serial echocardiograms suggested that the atria1 defect was small, a Blalock- Hanlon septectomy was performed with an improvement in oxygenation, Although it is unlikely that the prostaglandin Ei caused any increase in pulmonary blood flow (either through increased ductal shunting or decreased pulmonary resistance), it is possible that such an effect did occur; if so, perhaps the systemic arterial oxygen saturation did not increase because of a restrictive interatrial communication. Indeed, it would seem possible that deleterious effects could result from increased pulmonary venous pressure if there were a large pulmonary blood flow and a restrictive atria1 defect.

Site of prostaglandin El infusion: During this study, prostaglandin Ei was infused through an umbilical arterial catheter positioned at the level of the ductus arteriosus and through peripheral venous lines.


Early experience with prostaglandin Ei suggested that Therapeutic recommendations: On the basis of our intraarterial infusion at the site of the ductus arteriosus experience with these five infants, we recommend the was preferable in order to provide the highest concen- use of prostaglandin Ei in infants with d-transposition tration of prostaglandin Ei to the ductus arteriosus, to of the great arteries and intact ventricular septum when allow for rapid inactivation of the drug by the lungs and there is severe hypoxemia or acidosis, or both, after the to reduce side effects in the central nervous system.7 creation of an adequate interatrial communication and Our own experience in 32 infants as well as that of oth- when an open ductus arteriosus can be demonstrated. er+ does not support this view. We have not seen a If the interatrial defect is small after balloon atria1 relation between the site of infusion and its efficacy or septostomy, surgical creation of an interatrial commu- the appearance of adverse reactions. Because of the nication should be undertaken before treatment with potential for difficulties should a peripheral intravenous prostaglandin El. If prostaglandin Ei leads to im- line infiltrate, we recommend that a secure central ve- provement in clinical status, the treatment should be nous line be employed if the venous route of adminis- continued for as short a time as possible to allow for the tration is elected. normal decrease in pulmonary resistance.

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1978 Quaegebeur JM, Rohmer J, Brom AG, Tinkeienberg J: Revival of the Senning operation in the treatment of transposition of the great arteries. Thorax 32:517-524, 1977 Nadas AS, Fyier DC Pediatric Cardiology, Philadelphia, WB Saunders, 1972, p 609 Paul MH: D-transposition of the great arteries. In, Heart Disease in Infants, Children and Adolescents (Moss AS, Adams FH, Em- manouilides GC, ed). Baltimore, Williams & Wilkins, 1977, p 301-338 Egioff LP, Freed MD, Dick M, Norwood WI, Castaneda AR: Early and late results with the Mustard operation in infancy. Ann Thorac Surg 26~474-484, 1978 Bierman FZ, Williams RG: Subxiphoid two dimensional imaging of the atrial septum (abstr). Am J Cardiol 41:354, 1978 Mair DD, Riiter DG: Factors influencing intercirculatory mixing in patients with complete transposition of the great arteries. Am J Cardiol 30:653-658, 1972 Kadowitz PJ, Joiner PD, Hyman AL: Physiological and pharma- cological roles of prostaglandins. Ann Rev Pharmacol Toxicol 15:285-306, 1975 Cariaon LA, Ekeiund LO, Oro L: Circulatory and respiratory effects of different doses of prostaglandin El in man. Acta Physiol Stand 75:161-169, 1969 Lewis AS, Lurle PR: Prolonged prostagiandin El infusion in an infant with cyanotic congenital heart disease. Pediatrics 61:534-536, 1978 Lewis AB, Takahashi M, Lurle PR: Administration of prostaglandin El in neonates with critical cardiac defects. J Pediatr 93:481-485, 1978

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use of prostaglandin e1 in infants with d-transposition of the great arteries and intact ventricular...

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