Patients with Gram - negative sepsis often develop pulmonary edema because bacterial endotoxins increase pulmonary microvascular permeability. However endotoxins may also promote edema formation by limiting lung lymphatic flow. Lymphatic vessels help to prevent edema by removing excess fluid from the lung. Fluid is """"""""pumped"""""""" through the lymphatics by contractions of the lymphatic vessel smooth muscle and there is evidence that endotoxins may depress the lymphatic pump. This will be tested by cannulating a segment of lung lymphatic vessel. The relationship between the flow through the lymphatic and the pressure at the inflow to the lymphatic will be measured. This relationship will be used to assess the strength of the lymphatic pump before and after E. coli endotoxin. Endotoxin could also limit lung lymph flow by increasing the lymphatic flow from other tissues. Lung lymphatics interconnect with lymphatics from many other tissues before they drain into veins in the neck. Thus an increase in lymphatic flow from nonpulmonary tissues could interfere with lung lymphatic flow. This will be tested by determining the amount of edema caused by endotoxin in which most of the nonpulmonary lymphatics have been severed. If increases in lymphatic flow from nonpulmonary tissues do interfere with lung lymph flow, then these sheep should have less edema than control sheep with intact nonpulmonary lymphatics. The final studies are to determine if the lymphatics are more effective at removing edema fluid when the lymph is allowed to drain through a cannula. This will be tested by comparing the amounts of edema caused by endotoxin 1) with lung lymphatics and 2) controls sheep. The proposed studies should help to define the role of the pulmonary lymphatic system in the pulmonary edema caused by endotoxin.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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University of Texas Health Science Center Houston
Schools of Medicine
United States
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Gabel, J C; Dhother, S; Drake, R E (1994) Increased lymphatic pressure without increased neck vein pressure during intravenous infusions. Am J Physiol 266:R1596-8
Garewal, D; Gallagher, H; Drake, R E et al. (1993) Washout of protein in dog lung lymph. J Appl Physiol 75:1168-70
Drake, R E; Anwar, Z; Kee, S et al. (1993) Intestinal lymphatic pressure increases during intravenous infusions in awake sheep. Am J Physiol 265:R703-5
Gallagher, H; Garewal, D; Drake, R E et al. (1993) Estimation of lymph flow by relating lymphatic pump function to passive flow curves. Lymphology 26:56-60
Drake, R E; Gabel, J C (1992) Diaphragmatic lymph vessel drainage of the peritoneal cavity. Blood Purif 10:132-5
Gabel, J C; Drake, R E (1992) Increased venous pressure causes increased thoracic duct pressure in awake sheep. J Appl Physiol 73:654-6
Drake, R E; Abbott, R D (1992) Effect of increased neck vein pressure on intestinal lymphatic pressure in awake sheep. Am J Physiol 262:R892-4
Allen, S J; Fraser, R E; Laurent, U B et al. (1992) Turnover of hyaluronan in the rabbit pleural space. J Appl Physiol 73:1457-60
Drake, R E; Gabel, J C (1991) Effect of outflow pressure on intestinal lymph flow in unanesthetized sheep. Am J Physiol 260:R668-71
Drake, R E; Gabel, J C (1991) Estimation of the pulmonary microvascular reflection coefficient to protein in dogs. J Appl Physiol 71:94-8

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