Our previous studies have shown that endotoxin causes pulmonary edema by increasing pulmonary microvascular permeability and pressure (Pc). Our first objective will be to determine if reducing Pc will prevent edema after endotoxin. We will infuse E. coli endotoxin into unanesthetized sheep and prevent the rise in Pc with a vasodilator. We will estimate edema formation with the extravascular fluid/blood free dry weight ratio (EVF) and compare it to the EVF of sheep which receive endotoxin but no vasodilator. This study could lead to a better understanding of the effect of pulmonary hypertension on edema in septic patients. Pulmonary edema may also result from reduced lung lymph flow (Q-L) caused by elevated systemic venous pressure (SVP). For our second objective, we will study this by measuring Q-L and EVF in a group of sheep in which we elevate SVP. We will also elevate Pc in order to promote edema. A greater EVF and lower Q-L in the elevated SVP group compared to controls should indicate the degree to which venous pressure affects edema formation. For our final objective, we will investigate the phenomenon of proliferation of the lung lymph system when left atrial pressure is chronically elevated. We will increase left atrial pressure by 15 mmHg in sheep and measure Q-L for 2 months. Increases in Q-L over this time should allow us to evaluate the time course of lymph system proliferation and estimate its effect in preventing pulmonary edema. We will also perform morphological studies designed to determine the site of tissue fluid accumulation in these sheep. This study could help us to understand lung fluid balance in patients with chronically elevated pulmonary vascular pressures.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL027367-08
Application #
3339140
Study Section
Respiratory and Applied Physiology Study Section (RAP)
Project Start
1980-09-01
Project End
1989-11-30
Budget Start
1987-12-01
Budget End
1989-11-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
University of Texas Health Science Center Houston
Department
Type
Schools of Medicine
DUNS #
City
Houston
State
TX
Country
United States
Zip Code
77225
Drake, R E; Gabel, J C (1991) Estimation of the pulmonary microvascular reflection coefficient to protein in dogs. J Appl Physiol 71:94-8
Butler, B D; Drake, R E; Sneider, W D et al. (1990) Changes in microvascular permeability with acceleration of edema in dog lungs. Am J Physiol 258:H395-9
Elk, J R; Laine, G A (1990) Pressure within the thoracic duct modulates lymph composition. Microvasc Res 39:315-21
Dunbar, B S; Elk, J R; Drake, R E et al. (1989) Intestinal lymphatic flow during portal venous hypertension. Am J Physiol 257:G94-8
Butler, B D; Davies, I; Drake, R E (1989) Effect of lysophosphatidylcholine on the filtration coefficient in intact dog lungs. Am J Physiol 257:H1466-70
Allen, S; Gabel, J; Drake, R (1989) Left atrial hypertension causes pleural effusion formation in unanesthetized sheep. Am J Physiol 257:H690-2
Elk, J R; Drake, R E; Williams, J P et al. (1988) Lymphatic function in the liver after hepatic venous pressure elevation. Am J Physiol 254:G748-52
Gabel, J C; Allen, S J; Laine, G A et al. (1988) Fluid resuscitation in shock. Acta Anaesthesiol Belg 39:147-53
Drake, R E; Laine, G A (1988) Pulmonary microvascular permeability to fluid and macromolecules. J Appl Physiol 64:487-501
Allen, S J; Laine, G A; Drake, R E et al. (1988) Superior vena caval pressure elevation causes pleural effusion formation in sheep. Am J Physiol 255:H492-5

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