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Pulmonary microvascular injury from lipoxygenase infusion: comparison with endotoxemia
Abstract:
We compared the response of the pulmonary microcirculation to a 5-hr infusion of soybean lipoxygenase with that seen after endotoxin. We monitored microvascular integrity using lung lymph flow QL and lymph/plasma (L/P) protein ratio in unanesthetized sheep. We noted a twofold to threefold increase in QL and a slight decrease in L/P ratio beginning about 1 hr after onset of the lipoxygenase infusion. Leukocyte count decreased significantly and lymph lysosomal enzyme activity increased. Pulmonary artery pressure initially increased from 16 to 31 mm Hg, then decreased to 25 mm Hg during continued infusion. Platelet count remained constant. Parameters returned to baseline several hours after infusion. This pulmonary vascular pressure and lymph flow response was very similar to that seen in the increased permeability phase of endotoxin. A decrease on the L/P ratio and a constant rather than a decreased platelet count were findings different from those seen after endotoxin.
Insights
Soybean lipoxygenase infusion increased lung lymph flow and pulmonary artery pressure in sheep, mimicking endotoxin effects on microcirculation. However, platelet count changes differed, suggesting distinct inflammatory pathways.
Area of Science:
- Pulmonary Medicine
- Inflammation Research
- Microcirculation Studies
Background:
- Endotoxin is known to increase pulmonary microvascular permeability.
- Understanding inflammatory mediators is crucial for treating lung injury.
Purpose of the Study:
- To compare the pulmonary microcirculation response to soybean lipoxygenase infusion with that of endotoxin.
- To investigate the effects of lipoxygenase on lung lymph flow and microvascular integrity.
Main Methods:
- Unanesthetized sheep were infused with soybean lipoxygenase for 5 hours.
- Microvascular integrity was assessed by monitoring lung lymph flow (QL) and lymph/plasma (L/P) protein ratio.
- Pulmonary artery pressure, leukocyte count, and lymph lysosomal enzyme activity were also measured.
Main Results:
- Lipoxygenase infusion caused a 2-3 fold increase in QL and a slight decrease in L/P ratio.
- Pulmonary artery pressure initially rose and then decreased, while leukocyte count significantly decreased.
- Lymph lysosomal enzyme activity increased, and platelet count remained constant.
- The observed pulmonary vascular pressure and lymph flow responses were similar to the increased permeability phase of endotoxin.
Conclusions:
- Soybean lipoxygenase induces pulmonary microvascular changes comparable to endotoxin.
- Differences in L/P ratio and platelet count suggest distinct mechanisms of microvascular injury between lipoxygenase and endotoxin.
- Further research into lipoxygenase pathways may reveal novel therapeutic targets for lung inflammation.