Many of the proposed physiologic mechanisms thought to govern the effect of surfactant on gas exchange remain either unconfirmed or inadequately characterized in the intact human newborn infant. Without direct knowledge of the effects of surfactant treatment on lung function in human infants with hyaline membrane disease (HMD), our ability to answer questions related to dosing, comparative efficacy of different surfactant compositions, variation in response from patient-to-patient, and optimal ventilator settings during and following surfactant treatment, will be unduly handicapped. Acquisition of this information has been limited due to difficulties in measuring lung volume and indices of gas mixing such as alveolar ventilation in ventilator-dependent premature infants who are critically ill with HMD. The Vanderbilt Newborn Clinical Research Unit now has in operation a lung function measurement system based on a uniquely designed whole-body plethysmograph which allows these measurements to be made safely in ventilator-dependent premature infants in a newborn intensive care unit. The overall objective of this proposal is to provide an understanding of how a variety of physiologic effects of surfactant administration interact to yield the integrated clinical response seen at the bedside when a human premature infant with HMD is treated with surfactant.
The specific aims of this proposal are to develop a physiologic model of the effect of surfactant treatment, to evaluate the effect of type of surfactant preparation on response to treatment, to determine the effect of dosing interval on physiologic response to surfactant treatment, to design and test ventilator management protocols which will complement the effects of surfactant treatment, to incorporate micromechanical properties of the lung into the overall physiologic model of surfactant treatment effect, and to validate the application of thoracic impedance plethysmography to detect changes in lung water status in response to surfactant treatment.
These specific aims will be sought by measuring changes in the mechanical properties of the lung, in ventilation and key volume parameters, and in lung water status before and after treatment with surfactant. Two surfactant preparations, one protein containing (Survanta) and one which is synthetic and does not contain protein (Exosurf) will be studied at two dosing intervals. Validation of impedance plethysmography to assess changes in lung water status will be carried out in newborn lambs in which extravascular lung water and pulmonary blood volume are measured by indicator dilution analysis.
| Chroneos, Z C; Abdolrasulnia, R; Whitsett, J A et al. (1996) Purification of a cell-surface receptor for surfactant protein A. J Biol Chem 271:16375-83 |
| Watanabe, T; Oki, Y; Orth, D N (1989) Kinetic actions and interactions of arginine vasopressin, angiotensin-II, and oxytocin on adrenocorticotropin secretion by rat anterior pituitary cells in the microperifusion system. Endocrinology 125:1921-31 |
