Optimal management of patients with congenital heart disease often depends on the ability to monitor pulmonary hemodynamics and assess pulmonary vascular impairment. Need for improved techniques has prompted investigations of relationships between abnormal pulmonary circulations and pulmonary blood velocity patterns, which can be observed noninvasively with pulsed Doppler ultrasound. Features commonly associated with pulmonary hypertension are increased flow reversal in the main pulmonary artery and decreased acceleration time (time from onset of systole to peak velocity). However, recent studies indicate that acceleration time is primarily a function of arterial compliance; flow reversal is directly related to the curvature in the pulmonary outflow tract and/or peripheral vascular resistance. These findings imply that idealized relationships with pressure may exist only in the presence of expected, but not guaranteed, structural changes. Pulmonary vascular impairment is commonly associated with lack of response to vasodilators: however, changes in velocity profiles and the associated pulmonary input impedance spectra may be better indicators of responsiveness. This study will address these issues through experiments designed to identify and quantitate the determinants of the velocity profiles in animal models developed to produce the pulmonary vascular changes associated with either elevated pressure or flow from infancy through childhood. Newborn lambs will be chronically instrumented to measure pulmonary pressures, velocity profiles and axial dimensions from birth to 6 months of age. Elevated pulmonary artery pressure or blood flow will be produced via monocrotaline pyrrole injections or arteriovenous shunts, respectively. Acute interventions designed to assess changes in vascular reactivity will be made during data collection sessions. After natural histories are determined, the ability of long-term pharmacological interventions to alter the high pressure model history will be assessed. Data collected will be used to determine 2- and 3- dimensional velocity profiles, resistance, compliance and shape changes and input impedance spectra. After the terminal hemodynamic study, casts of the right ventricle and proximal pulmonary arteries will be made in situ under hemodynamically matched systolic pressure. The casts will be CT scanned and their structure committed to computer memory, from which 2- and 3-dimensional images can be reconstructed. Algorithms will be developed for quantifying curvature and torque of the main trunk, flow divider offset, taper, bifurcation angles, and segment dimensions. Experiments designed to test instrumentation and to determine the effects of changes in peripheral vascular resistance as a result of selective embolization of individual lungs will be conducted in acute preparations. Techniques for measuring the pulmonary input impedance spectrum and extracting its salient features will be developed using simple models of the pulmonary vascular bed. Finally, results obtained in the animal models will be compared to available clinical data, thus testing the belief that better understanding of the determinants of the velocity profile will lead to improved patient diagnosis and care.
