Suddenly induced intravascular aggregation of platelets and vascular injury

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It has been well documented that vessel injury elicits a formation of platelet thrombi. When the subendothelium is exposed to blood stream, platelets adhere to subendothelial components, mainly to collagen. On the contrary recent reports indicate that an opposite sequence may take place that platelet aggregation in the circuration may damage a normal vascular wall. However evidence is still scant and the mechanism is not clear. Adenosine diphosphate (ADP) is a principal aggregating agent of the platelet and the ADP-induced platelet aggregation in the circulation is usually reversible. This type of platelet aggregation has been thought to be a frequent clinical occurcnce in various atherosclerotic and thrombotic situations. In this paper effects of ADP-induced intravascular aggregation of the platelet on the pulmonary artery were studied.Materials and Methods: Twenty-eight male rabbits were used. In 4 of them thrombocytopenia was induced (less than 5×104/μl) by anti-rabbit-platelet guinea pig serum (APS). Seven of 28 were pretreated with acetylsalicylic acid (ASA). All animals were injected with ADP (2-5mg/kg) into the central vein in several seconds under pentobarbital anesthesia. Heart rate, respiration, ECG, systemic arterial and central venous pressures were recorded continuously throughout the experiment. After an observation for one hour animals were sacrificed by overdose of pentobarbital and sections of the lungs were examined by light microscope.Results: Immediately after ADP injection the rabbits developed marked bradycardia, premature beats, ischemic ST-T changes and convulsion followed by tachypnea for several minutes. Hypotension and rise in central venous pressure were also noted. Platelet count decreased immediately after ADP injection and increased at 10 minutes. In both APS and ASA pretreated animals above changes were absent or very slight and platelet count did not change significantly. Histology of the lungs revealed that platelet aggregates were very frequently present in small and medium sized pulmonary arteries associated with luminal narrowing, thickening of muscular media, swelling of endothelial cells and characteristic micro-cysts in the intima (Figures 1 and 2). Occasional hemorrhagic infarcts were also seen. These changes were totally absent in APS induced thrombocytopenic rabbits and significantly slight in ASA pretreated ones (Table 1).Comments: The result shown in Figures 1 and 2 would suggest a contraction of the pulmonary artery and a damage of the endothelium associated with platelet aggregation. Recent development in pharmacology of the platelet elucidated that platelet aggregates release potent platelet-aggregating and vasoconstrictive substances, prostaglandin endoperoxides and thromboxane A2. The pulmonary arterial contraction and injury are apparently elicited by the platelet aggregation and the pretreatment with ASA which inhibits cyclooxygenase, the enzyme transforms arachidonic acid to PG endoperoxides, prevented these changes. As a consequence the changes in the pulmonary artery might be induced by PG endoperoxides and thromboxane A2 as well as serotonin.