One of the most life-threatening clinical conditions in respiratory medicine today is pulmonary edema, in which an accumulation of fluid in the lung tissue greatly impedes the diffusion of oxygen and carbon dioxide between the blood and lung air. Current research in non-mammalian lung physiology indicates that alternative, non-traditional models may provide new insights into the treatment of pulmonary edema. Rates of pulmonary fluid filtration in non-diseased amphibians and reptiles equal or exceed those of humans afflicted with pulmonary edema, suggesting that these non-mammalian vertebrates """"""""naturally"""""""" possess the same proximal factors that cause pulmonary edema in human (leakiness of lung blood vessels and/or pulmonary hypertension). However, these lungs in lower vertebrates are not edematous. Why these animals sustain such high rates of lung fluid filtration and how they avoid fluid edema are compelling questions whose answers may prove useful in the search for more effective treatments of pulmonary edema. Accordingly, the goals of the proposed study are to 1) determine the physiological basis for such high pulmonary filtration rates in lower vertebrates (leakiness and/or hypertension) and 2) discover the mechanism(s) used by these animals to prevent the accumulation of excess lung fluid. Established techniques of isolated lung perfusion will be applied to two species (marine toad and pond turtle) to determine the comparative """"""""leakinness"""""""" of the pulmonary capillary (hydraulic conductivity, capillary isogravimetric pressure, and osmotic reflection coefficient). Measurements of the transcapillary Starling forces (hydrostatic and oncotic pressures) will also be measured to determine if a """"""""filtration bias"""""""" exists in lower vertebrate lungs due to pulmonary hypertension. Finally, the role of positive intrapulmonary pressure that mechanically massages fluid out of the lung will be tested as a possible edema-preventing mechanism in toads and turtles using a tracer study to quantify rates of lymphatic return.
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| Daniels, C B; Orgeig, S; Smits, A W et al. (1996) The influence of temperature, phylogeny, and lung structure on the lipid composition of reptilian pulmonary surfactant. Exp Lung Res 22:267-81 |
| Daniels, C B; Orgeig, S; Smits, A W (1995) The composition and function of reptilian pulmonary surfactant. Respir Physiol 102:121-35 |
| Smits, A W; Orgeig, S; Daniels, C B (1994) Surfactant composition and function in lungs of air-breathing fishes. Am J Physiol 266:R1309-13 |
| Orgeig, S; Daniels, C B; Smits, A W (1994) The composition and function of the pulmonary surfactant system during metamorphosis in the tiger salamander Ambystoma tigrinum. J Comp Physiol B 164:337-42 |
