Pulmonary fibrin deposition and increased microvascular permeability to protein following fibrin microembolism in dogs: a structure-function relationship.
The effects of fibrin microembolism were examined using an infusion of a prothrombin activator (Echis carinatus venom, ECV; 30 min, 0.5 NIH thrombin equivalent units/kg) in acute mongrel dogs prepared with a pulmonary lymph cannula (n = 6, 12.3-21.5 kg). Lymph flow increased approximately 2.5-fold after 1-1.5 hr of elevated left atrial pressure (Pla = 20 cm H2O; 26 +/- 7 to 63 +/- 16 microliter/min, P less than 0.01) and the plasma to lymph protein concentration ratio (CP/CL) declined from 0.66 +/- .04 to 0.54 +/- .16 (P less than 0.01, x +/- SE). After Pla was reduced to control levels, the initiation of fibrin microembolism was associated with an approximate 2.7-fold elevation of lymph flow (62 +/- 8 microliters/min, P less than 0.01) and the CP/CL was not changed (0.56 +/- 0.04, P = ns). When Pla was increased following microembolism, lymph flow more than doubled to 117 +/- 24 microliter/min (P less than 0.01) and the CP/CL remained unaltered (0.56 +/- 0.03, P = ns). These changes were associated with afibrinogenemia and the appearance of fibrin degradation products (FDP) in plasma (150 +/- 50 micrograms/ml) and lymph (80 micrograms/ml) in three of the animals tested. No consistent pattern was seen in the CL/CP of separate endogenous plasma proteins after each intervention. These data support the view that pulmonary fibrin microembolism without inhibition of the fibrinolytic system was associated with an early increased pulmonary microvascular permeability to protein. In a separate group of similarly prepared animals (n = 8, 13-21.5 kg) without a lymph catheter, scanning electron microscopic observations showed branching fibrin microemboli to partially occlude some pulmonary arterioles. Mixed thrombus formations in larger precapillary blood vessels were also seen. Ultrastructural observations revealed the deposition of fibrin strands (periodicity = 220-230 A) within the pulmonary capillaries. Some of these deposits were overlaid by lamellar pseudopodia from endothelial cells and the fibrin appeared to be within these cells. Although plasmalemmal vesicles seemed to be more numerous in the endothelial cells with adjacent fibrin deposits, no gaps or breaks were seen in the densely stained interendothelial cell junctions and/or the endothelial cell membrane of the affected lung capillaries. Activated neutrophils and platelets were more numerous in the pulmonary capillaries following EVC. These data suggest that the presence of FDP and/or fibrin deposits within the pulmonary microvasculature may influence the early functional integrity of pulmonary endothelial cells at sites of fibrin accumulation.
Schaeffer
R C
RC
Barnhart
M I
MI
Carlson
R W
RW
D000818:Animals; D001794:Blood Pressure; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology / Q000648:ultrastructure; D002199:Capillary Permeability; D004285:Dogs; D004591:Electrophoresis, Polyacrylamide Gel; D010450:Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology; D004727:Endothelium / Q000502:physiology; D005337:Fibrin / Q000378:metabolism*; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000098:blood supply* / Q000166:cytology / Q000378:metabolism; D008208:Lymphatic System / Q000187:drug effects; D008833:Microcirculation / Q000502:physiology* / Q000648:ultrastructure; D008855:Microscopy, Electron, Scanning; D010949:Plasma / Q000502:physiology; D011651:Pulmonary Artery / Q000503:physiopathology / Q000648:ultrastructure; D011655:Pulmonary Embolism / Q000139:chemically induced / Q000503:physiopathology*; D013329:Structure-Activity Relationship
D005337:Fibrin; D010450:Endopeptidases; C020097:ecarin