• O D Pedersen, J Gram, H Bagger, N Keller, and J Jespersen.
• Departments of Clinical Chemistry, Ribe County Hospital, Esbjerg, Denmark.
• Coron. Artery Dis. 1994 Jul 1; 5 (7): 617-23.

BackgroundImpaired endogenous tissue-type plasminogen activator (t-PA)-mediated fibrinolysis may be involved in the evolution of myocardial infarction. t-PA-mediated fibrinolysis is believed to depend on the amount of active t-PA present in the circulation. Accordingly, we investigated the possible mechanisms responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease.MethodsForty-five survivors of acute myocardial infarction were examined 8 weeks after discharge from hospital. Intravenous infusion of 1-desamino-8-D-arginine vasopressin (DDAVP; 0.4 micrograms/kg bodyweight) was used to stimulate the endogenous fibrinolytic system, and blood samples were collected before and after infusion. We compared the response of the t-PA-plasminogen activator inhibitor type-1 (PAI-1) fibrinolytic system in patients with preinfusion levels of active t-PA below or at the detection limit of the assay with that in patients with higher preinfusion levels of active t-PA.ResultsAll patients responded to DDAVP infusion with an increase in plasma concentration of t-PA antigen. This response did not differ between the two groups. In contrast, the preinfusion levels of PAI activity were significantly higher in patients with undetectable plasma levels of active t-PA compared with patients with higher levels of active t-PA (22.3 versus 12.8 IU/ml; P < 0.01). Subgroup analyses demonstrated that patients treated with diuretics had significantly higher plasma concentrations of PAI-1 antigen (28.5 versus 17.9 ng/ml; P < 0.03) and a trend towards higher PAI activity (24.0 versus 14.6 IU/ml; P = 0.07) compared with patients not receiving diuretics.ConclusionOur study strongly suggests that a high plasma level of PAI-1, the main inhibitor of t-PA, is responsible for impaired t-PA-mediated fibrinolysis in patients with ischaemic heart disease, and that treatment with diuretics may be associated with an unfavourable effect on the fibrinolytic system.

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