Platelet Sequestration In Lungs Research Articles

Hyperoxia induces platelet activation and lung sequestration: an event dependent on tumor necrosis factor-alpha and CD11a.

Mice were exposed to pure oxygen for various times to explore the pulmonary platelet trapping associated with alveolar damage, its mechanism, and its role in the lesions. Platelet sequestration, evaluated by electron microscopy and by injection of radiolabeled platelets, was detectable after 72 h and reached a maximum after 96 h of exposure (i.e., shortly before death). Circulating platelets (analyzed by Facscan) showed some increase in the expression of CD11a and CD62, but little change in CD31 and CD61. Both platelet activation and lung sequestration were dependent on TNF-alpha, since antibody against TNF-alpha reduced the expression of CD11a on circulating platelets and their sequestration in the lung. Lung platelet sequestration was also decreased by anti-CD11a MoAb. Northern blot analysis of lung mRNA isolated at 96 h of oxygen exposure revealed a 7-fold increase in CD54 (intercellular adhesion molecule-1 [ICAM-1]) and a 2.5-fold increase in TNF-alpha mRNAs respectively. These results demonstrate that the platelet pulmonary trapping induced by hyperoxia is dependent upon TNF-alpha and the CD11a-CD54 adhesion molecules. However, platelet trapping does not appear to play an important pathogenic role in acute oxygen injury, since treatments that decrease trapping (anti-TNF-alpha, anti-CD11a, or antibody-induced thrombocytopenia) did not markedly attenuate the alveolar damage.

Evaluation of Pulmonary Accumulation of 51Chromium-Labelled Rat Platelets following Intravenous Application of ADP and Collagen

We examined the effects of ADP- and collagen-induced pulmonary platelet embolism in the rat. Homologous 51Chromium-labelled platelets were used to monitor extracorporally the distribution of platelets in the circulation. For that purpose, collimated iodide scintillation detectors were placed above thorax (C1) and abdomen (C2). A dose-dependent increase in thoracic radioactivity, paralleled by a decrease in the abdomen, was observed after intravenous injection of ADP and collagen. This resulted in a shift of C1/C2, so that the effect of collagen was more pronounced (maximal increase of C1/C2 = 134%) than ADP (maximal increase of C1/C2 = 79%). The increase in thoracic radioactivity was caused by the uptake of platelets in the lung as was shown after administration of collagen (6-fold enrichment of labelled platelets). Lung platelet sequestration resulted in a dose-dependent thrombocytopenia. The ADP -and collagen-induced pulmonary platelet embolism reversibly provoked cardiovascular symptoms of shock: hypotension and bradycardia. Impaired gas exchange during platelet accumulation manifested itself in a reversible arterial hypoxaemia and hypercapnia, followed by a weak acidosis. We were able to inhibit ADP-dependent thoracic platelet accumulation by ticlopidine in a dose-related manner as well as collagen-induced thoracic platelet accumulation by acetylsalicylic acid. The results indicate that behaviour of homologous labelled rat platelets in vivo can easily be monitored, thus offering the opportunity to investigate the effects of antiaggregatory drugs on platelets in their natural environment.

Determinants of platelet kinetics: effects of pulmonary microembolism.

We examined the mechanisms of platelet uptake in the lungs after alpha-thrombin-induced pulmonary microembolism. Platelets labeled with 111In-oxine were reinfused into chronically prepared sheep. Pulmonary microembolism resulted in an increase in lung platelet radioactivity (95.5 +/- 15.3%; n = 4), which was followed by an exponential washout (half-life = 115 +/- 4 min). Platelet uptake in the lungs was more sustained after prior fibrinolytic inhibition with tranexamic acid (half-life = 178 +/- 11 min), although the initial increase was similar (90.7 +/- 9.6%; n = 7). Prior depletion of fibrinogen with ancrod (Arvin), blunted the initial increase in lung platelet uptake after alpha-thrombin challenge (31.7 +/- 11.3%, n = 5), indicating that the effect of thrombin was markedly dependent on fibrinogen. We examined the role of circulating granulocytes, since platelets may bind to subendothelial matrix exposed after granulocyte-mediated lung vascular injury. Maximal pulmonary platelet uptake after thrombin in granulocytopenic sheep was not different from control (71.7 +/- 14.4%; n = 4). The results indicate that pulmonary microembolism results in lung platelet sequestration. Platelet uptake is not dependent on granulocyte-mediated vascular injury but requires fibrin deposition and is sustained if fibrinolysis is inhibited.

Early and late platelet sequestration in different organs during endotoxic shock.

Using a sheep model, platelet sequestration in lungs, liver, kidney, spleen, and brain was studied after the injection of Indium-111-oxine-labeled platelets and E. coli lipopolysaccharide. Immediately following endotoxin-induced shock, platelet sequestration was observed in lungs, liver, and kidney with corresponding decrease in measured Indium-111-oxine platelets in spleen and circulating blood. There was also a decrease in platelet counts as measured in a phase contrast microscope. The early platelet sequestration in lung, liver, and kidney was followed by platelet disaggregation and another phase of platelet sequestration which continued until the death of the animal. No platelet sequestration was observed in the brain.

Platelet sequestration in lung with hemorrhagic shock and reinfusion in dogs.

We compared red blood cell (RBC) and platelet transit through the pulmonary vascular bed under control conditions (n = 8) and during hemorrhagic shock (n = 8) in anesthetized spontaneously breathing dogs, using a modification of the indicator-dilutor technique. Platelets and RBCs from each animal were labeled with 51Cr and 99mTc, respectively, and were rapidly injected into the right atrium while blood was sampled from the ascending aorta. The mean transit time (MTT), volume of distribution, and percent recovery for RBCs and platelets were calculated, as was the percent extraction of platelets. We found 1) the the difference between RBC and platelet MTT increased (p less than 0.01), 2) that the percent extraction of platelets increased (p less than 0.001), and 3) that the percent recovery of platelets fell (p less than 0.01) during the shock period. These values all returned to control levels after reinfusion of the shed blood. The relationship between a transient reduction in blood flow and platelet extraction was then studied in a third group of dogs (n = 5) where inflation of a balloon in the inferior vena cava was used to reduce cardiac output (CO). These studies showed that platelet extraction was inversely related to CO. We conclude that the increased platelet sequestration seen in the lung during hemorrhagic shock is primarily related to decreased blood flow.