Gas exchange is the primary function of the pulmonary circulation. Therefore, it would be advantageous if this function were to be achieved with minimal energy expenditure. Because of the pulsatility of the pulmonary circulation, wave reflection in the pulmonary arterial tree is inevitable. Wave reflection is important because it has an adverse effect on the hydraulic power that is delivered into the main pulmonary artery (MPA) from the right ventricle. Previous work indicates that characteristic impedance is an important determinant of wave reflection and altered by neurohumoral mechanisms. Therefore modulation of characteristic impedance may represent a way of controlling wave reflection. Characteristic impedance is dependent on the dimensions and the elasticity of the MPA. The dimensions of the MPA depend not only on transmural pressure, but also on flow. It is generally believed that the increased blood flow is detected by the increased shear rate on the endothelium. Therefore endothelial dependent mechanisms may be involved in the regulation of wave reflection. The overall objective of the proposed work is to determine the mechanisms involved that control the dimensions and elasticity of the MPA. It is proposed to measure the pressure, diameter and length of a segment of MPA in both awake and anesthetized dogs so that changes of dimensions and elasticity of this vessel can be calculated.
The specific aims of this project are as follows: (1) to determine the independent effects of pressure and flow on both the elasticity and the dimensions of the MPA, and the extent to which they are modulated by increased smooth muscle tone, autonomic receptors, cyclooxygenase products and nitric oxide production in anesthetized dogs; (2) to determine the role of autonomic receptors, cyclooxygenase products and nitric oxide production on the MPA during an acute circulatory disturbance in awake dogs, (3) to determine the relation between the changes of dimensions and elasticity of the MPA due to increased pulmonary vascular tone; and (4) to determine the effects of anesthesia on endothelial dependent mechanisms in the MPA. It is hoped that the results of these experiments ultimately will lead to the identification of therapeutic modalities to minimize the deleterious effects of wave reflection on pulmonary hemodynamics in lung disease.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL041011-06
Application #
2219848
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1988-09-01
Project End
1996-03-31
Budget Start
1994-04-01
Budget End
1996-03-31
Support Year
6
Fiscal Year
1994
Total Cost
Indirect Cost
Name
State University of New York at Buffalo
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
038633251
City
Buffalo
State
NY
Country
United States
Zip Code
14260
Magalang, U J; Grant, B J (1995) Determination of gas exchange threshold by nonparametric regression. Am J Respir Crit Care Med 151:98-106
Klocke, R A; Schunemann, H J; Grant, B J (1995) Distribution of pulmonary capillary transit times. Am J Respir Crit Care Med 152:2014-20
Li, Z; Grant, B J; Lieber, B B (1995) Time-varying pulmonary arterial input impedance via wavelet decomposition. J Appl Physiol 78:2309-19
Lieber, B B; Li, Z; Grant, B J (1994) Beat-by-beat changes of viscoelastic and inertial properties of the pulmonary arteries. J Appl Physiol 76:2348-55
Grant, B J (1994) Noninvasive tests for acute venous thromboembolism. Am J Respir Crit Care Med 149:1044-7
Grant, B J; Canty Jr, J M; Srinivasan, G et al. (1993) Pulmonary arterial elasticity in awake dogs. J Appl Physiol 75:840-8
Grant, B J; Lieber, B B (1992) Compliance of the main pulmonary artery during the ventilatory cycle. J Appl Physiol 72:535-42
Grant, B J; Fitzpatrick, J M; Lieber, B B (1991) Time-varying pulmonary arterial compliance. J Appl Physiol 70:575-83
Grant, B J; Sherif, S M (1991) Flow-mediated vasodilatation of the main pulmonary artery. Respir Physiol 86:77-90
Fitzpatrick, J M; Grant, B J (1990) Effects of pulmonary vascular obstruction on right ventricular afterload. Am Rev Respir Dis 141:944-52

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