NEONATAL PULMONARY ISCHEMIA

Part I: Clinical and Physiological Studies

¹ Departments of Pediatrics, Western Reserve University School of Medicine and Mt. Sinai Hospital, Cleveland, Ohio.
² Cardiovascular Research Institute and Department of Pediatrics, University of California Medical Center, San Francisco; Career Investigator, American Heart Association.
³ Department of Pediatrics, University of Colorado Medical School, Denver, Colorado.
⁴ Department of Pediatrics, Western Reserve University School of Medicine, Cleveland, Ohio.
⁵ Departments of Pediatrics, Western Reserve University School of Medicine and Metropolitan General Hospital, Cleveland, Ohio.
⁶ Cardiovascular Research Institute and Department of Pediatrics, University of California Medical Center, San Francisco, California; John and Mary Markle Scholar in Academic Medicine.

We made detailed observations of the cardiopulmonary manifestations of the respiratory distress syndrome in 27 infants. In most respects these confirmed observations reported by other investigators.

Expiratory complaint was a major feature of the disease, and its effects on cardiac input and on the work of breathing have been discussed. It may have been the result of reflexes initiated in the pulmonary vessels when they were strongly stimulated to constrict.

Infants with severe respiratory distress showed systemic hypotension, cutaneous vasoconstriction, oliguria, and ileus.

They usually had slightly increased minute volume. Lung compliance and volume and the ratio of compliance to lung volume were decreased, but respiratory resistance was normal. Apparent physiological deadspace was greatly elevated, and apparent alveolar ventilation was therefore greatly decreased. Arterial oxygen tension was below the predicted values, and there was moderate to very large fractional right-to-left shunt which appeared to occur principally through the foramen ovale and to a lesser extent through the ductus arteriosus. There was both respiratory and metabolic acidosis.

Effective pulmonary blood flow was often strikingly reduced, as was cardiac input, roughly estimated from effective pulmonary blood flow and fractional right-to-left shunt.

Administration of dipalmitoyl lecithin as an aerosol was followed by increase in lung compliance, which occurred even in those infants who died.

Infusion of acetylcholine caused a rapid, large increase in effective pulmonary blood flow accompanied by a marked rise in estimated cardiac input, a decrease in fractional right-to-left shunt, an increase in carbon dioxide elimination, alleviation of expiratory complaint, an increase in cutaneous blood flow and an increase in responsiveness and motor activity.

We conclude that these infants had marked pulmonary vasoconstriction and ischemia because they had low effective pulmonary blood flow when the right ventricular pressure was normal and because acetylcholine rapidly increased effective pulmonary blood flow with a drop in right ventricular pressure. Pulmonary ischemia was present early in the disease.

We also conclude that these infants had low systemic blood flow, especially in the renal, mesenteric, and cutaneous vascular beds, and that administration of acetylcholine and increase in pulmonary blood flow brought about a rise in the estimated cardiac input and a more normal distribution of systemic flow.

Because administration of dipalmitoyl lecithin was followed by an increase in lung compliance, even in infants whose gas transfer was not improved and who died, and infusion of acetylcholine caused prompt improvement in gas transfer, blood flow, and clinical status without simultaneous increase in lung compliance, volume or ventilation, we conclude that ischemia in pulmonary and certain systemic vascular beds may have presented greater functional difficulty to these infants than did pulmonary atelectasis and hyaline membranes.

In this study ACh was used to demonstrate a mechanism, and, in our opinion, a firm recommendation for use of ACh (or other pulmonary vasodilator) in this syndrome must await a convincing test carried out with proper experimental design in a sufficiently large number of subjects.

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