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Bovine tendon collagen suspension (4.5 mg/kg) was injected rapidly into the femoral vein of 14 normal (untreated) and 8 busulfan treated rats. Trasient effects included decreased platelet counts and arterial PO2, increased central venous pressure, apnea, bradycardia and variable A-V block. These findings were most prominent within 1 minute after injection and subsided or disappeared by 10 minutes. During this period, ADP and ATP in platelet-free plasma from carotid arterial blood were measured in a liquid scientillation counter using the firefly luciferase assay. In normal (untreated) rats, collagen injection was followed by increases in plasma ADP and ATP, a rise in plasma hemoglobin and minimal changes of fibrinogen and hematcrit. Pathological observations indicated the platelet emboli in pulmonary vessels. In contrast, rats made thrombocytopenic by intraperitoneally infected busulfan prior to collagen injection had minimal or no change in platelet count, plasma ADP, ATP, hemoglobin, fibrinogen, or cardiopulmonary functions following collagen injection. These findings suggest that collagen injection causes release of ADP and ATP from platelets; released ADP induces platelets to form aggregates which lodge in the coronary and pulmonary microcirculations and elsewhere, resulting in thrombocytopenia and the cardiopulmonary dysfunction, in the presence of shear, of red cells with vessel surfaces altered by platelet aggregates.

CARDIOPULMONARY DYSFUNCTIONS CAUSED BY INTRAVENOUS COLLAGEN-INDUCED RELEASE OF ADP AND ATP FROM PLATELETS