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.
Showing the most recent 10 out of 30 publications
