Lung morphological and permeability changes induced by intravascular coagulation in dogs.
The objectives of this study were to describe the morphological alterations of the pulmonary microvasculature in anesthetized dogs infused intravenously with alpha-thrombin (111-233 NIH U/kg) and to measure the protein reflection coefficient (sigma d), an index of pulmonary vascular permeability to proteins. Quantitative electron microscopy of lung biopsies from a group of four dogs showed an increase in the volume density of the alveolar interstitium and an increase in intravascular fibrin at 30 min after the thrombin infusion. The pulmonary microvascular endothelium was often swollen, blistered, highly vacuolized, or rarefied when close to or in contact with fibrin but appeared normal when not closely associated with fibrin. Fibrin-endothelial interactions often included projections of endothelium surrounding fibrin, the presence of fibrin within endothelial cells, 10- to 15-nm bridges connecting fibrin and endothelium, and disruption of the endothelial plasmalemma in contact with fibrin. Alveolar epithelial cells were unaffected by the thrombin infusion. Pulmonary lymph was collected from an afferent lymphatic to the left tracheobronchial lymph node in a second group of five dogs anesthetized with pentobarbital sodium intravenously. Thrombin increased pulmonary lymph flow by sevenfold and also increased the extravascular lung water-to-bloodless dry lung weight ratio. Left atrial pressure was elevated after thrombin infusion until a filtration-independent state was approached for the calculation of sigma d. Thrombin decreased sigma d from a normal value of 0.62 +/- 0.02 to 0.53 +/- 0.02. Thus thrombin-induced intravascular coagulation in dogs produced focal disruptions of the microvascular endothelium associated with intravascular fibrin and increased the pulmonary vascular permeability to proteins.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects; D004285:Dogs; D004903:Erythrocyte Aggregation / Q000473:pathology* / Q000503:physiopathology; D005337:Fibrin / Q000378:metabolism; D006098:Granulocytes / Q000473:pathology; D008168:Lung / Q000473:pathology* / Q000503:physiopathology; D008196:Lymph / Q000502:physiology; D008854:Microscopy, Electron; D011506:Proteins / Q000378:metabolism; D011652:Pulmonary Circulation / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013917:Thrombin / Q000494:pharmacology; D014148:Tranexamic Acid / Q000494:pharmacology
D011506:Proteins; D014148:Tranexamic Acid; D005337:Fibrin; D013917:Thrombin