Vasoactive agents and production of thrombosis during intravascular coagulation 1--comparative effects of norepinephrine in thrombin and adenosine diphosphate (ADP) treated rabbits.
Pathogenesis of the microthrombi produced during intravascular coagulation was investigated in rabbits given intravenous infusions of thrombin or adenosine diphosphate (ADP). Thrombin, at a dosage producing a fibrinogen consumption of 70% within 4 h (1 unit/kg/min), failed to produce extrapulmonary microthrombi unless fibrinolysis inhibition (epsilon-aminocaproic acid-EACA) or alpha-adrenergic stimulation (norepinephrine) were provided simultaneously. The mechanism whereby norepinephrine initiated glomerular capillary thrombosis was not related to interference with fibrinolysis nor to potentiation of platelet aggregation and blood coagulation, as indicated by similar consumption of plasminogen and platelets in animals given thrombin alone or combined with norepinephrine, and by the lack of correlation between fibrinogen consumption and the incidence and severity of glomerular thrombosis produced with various dosages (1 to 3 mu/kg/min) of norepinephrine. With norepinephrine, microthrombi were also observed in the adrenals, the spleen and the gastric mucosa. Aspirin prevented the phenomena in the latter two organs, but was inactive or aggravating on thrombogenesis elsewhere. ADP associated with thrombin failed to trigger formation of microthrombi but initiated platelet-rich thrombi in the pulmonary vasculature when associated with norepinephrine. We conclude that unlike thrombin, ADP cannot be held responsible for the microthrombi elicited during experimental intravascular coagulation. Furthermore, the ability of norepinephrine to elicit glomerular thrombosis in thrombin injected rabbits may provide an explanation for requirement of alpha-adrenergic stimulation in the endotoxin-induced generalized Shwartzman reaction.
D000244:Adenosine Diphosphate / Q000494:pharmacology*; D000255:Adenosine Triphosphate / Q000494:pharmacology; D015119:Aminocaproic Acid / Q000494:pharmacology; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D004211:Disseminated Intravascular Coagulation / Q000097:blood*; D009638:Norepinephrine / Q000494:pharmacology*; D011817:Rabbits; D012790:Shwartzman Phenomenon / Q000097:blood; D013917:Thrombin / Q000494:pharmacology*; D013927:Thrombosis / Q000097:blood / Q000209:etiology*
D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D013917:Thrombin; D001241:Aspirin; D015119:Aminocaproic Acid; D009638:Norepinephrine