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To test whether platelets are necessary for the increased vascular permeability associated with microemboli, we used 16 anesthetized sheep in which we measured lung lymph flow, pulmonary arterial and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentration. Injecting glass bead microemboli (200 micrometers diam) until pulmonary vascular resistance increased to three times base-line values caused lung lymph flow to increase at nearly constant lymph-to-plasma protein concentration ratio that is characteristic of increased microvascular permeability. Antiplatelet serum alone caused transient increases in pulmonary vascular resitance and lung lymph flow, but produced no change in steady-state lung fluid balance. After depleting platelets by greater than 97%, tripling pulmonary vascular resistance with emboli resulted in increases in lung lymph and protein flow comparable to that seen in untreated sheep. We injected twice the amount of beads in thrombocytopenic sheep compared to untreated sheep. We conclude that, although platelets do augment the pulmonary hypertension after emboli, they are not essential for the microemboli vascular injury.

Unilateral hyphema, hematuria, and ecchymoses developed in a previously healthy 42-year-old women after the ingestion of aspirin and ethanol. There was no evidence for ocular trauma, disease, or vascular malformation by slit-lamp examination and gonioscopy. Platelet count and coagulation tests were normal. The patient's bleeding time was prolonged and there was impaired platelet aggregation. Delayed (secondary) aggregation in response to collagen, adenosine diphosphate, and epinephrine was decreased, as was aggregation induced by thrombin and serotonin. These data indicate that the qualitative platelet defect was induced by both aspirin and ethanol. Anterior chamber hemorrhage subsided after discontinuation of aspirin and ethanol, and the hyphema subsequently resolved. Bleeding time and platelet aggregation were normal two weeks after the patient's initial presentation. A prolonged bleeding time in association with normal platelet count, prothrombin time, and partial thromboplastin time indicated a qualitative platelet defect, which is most commonly drug-induced. Defective platelet function resulted in spontaneous hyphema.

Investigators have proposed that fibrinogen, fibrin, or their degradation products are essential for the increased lung vascular permeability to fluid and protein that may occur after microemboli. To test this hypothesis, we used 20 anesthetized ventilated sheep in which we measured lung lymph flow, pulmonary artery and left atrial pressures, thermodilution cardiac output, and lymph/plasma protein concentrations. We injected glass bead microemboli (200 micrometers diam) sufficient to raise pulmonary vascular resistance to three times base-line values and cause increased lung lymph flow with a parallel increase in protein clearance, which is characteristic of increased lung vascular permeability. Neither large doses of heparin (3,000 U/kg) nor fibrinogen depletion with viper venom (ancrod, 2 U/kg), by themselves, affected steady-state pulmonary hemodynamics or lung fluid balance. These treatments prior to giving sufficient amounts of emboli to triple the pulmonary vascular resistance did not prevent the increased lung vascular permeability. We conclude that neither fibrin deposition nor degradation are essential to microembolic lung vascular injury in sheep.

We measured the regional distribution of pulmonary extravascular water to test our prediction that, because of higher vascular hydrostatic pressure in more dependent zones, the bottom of the lung would tend to be wetter than the top. We injected eight normal sheep under halothane anesthesia with 125I-labeled albumin and killed them 5 min later. We suspended the sheep in the prone position and froze them solid in dry ice. We sawed the thorax into horizontal slices, chipped the frozen lung from each, and determined extravascular lung water and hematocrit. Hematocrit was calculated from separately measured red blood cell (tissue hemoglobin) and plasma (125I-albumin) masses. We found regional extravascular water was constant throughout the lung. Regional hematocrit was significantly higher at the lung base than at the apex in these slowly frozen sheep after death. Calculation of extravascular water using a single blood mass marker (hemoglobin) underestimated lung water, more so at the base than at the apex, because blood mass was overestimated. Accurate measurement of blood mass is critical in the calculation of regional lung water.