Regulation of tissue-type plasminogen activator-mediated fibrinolysis by plasminogen activator inhibitor type-1 in patients with ischaemic heart disease: possible unfavourable effect of diuretics.
BACKGROUND
Impaired 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.


METHODS
Forty-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.


RESULTS
All 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.


CONCLUSIONS
Our 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.
Pedersen
O D
OD
Departments of Clinical Chemistry, Ribe County Hospital, Esbjerg, Denmark.
Gram
J
J
Bagger
H
H
Keller
N
N
Jespersen
J
J
D000368:Aged; D003894:Deamino Arginine Vasopressin; D004232:Diuretics / Q000009:adverse effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005342:Fibrinolysis; D006801:Humans; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood; D017202:Myocardial Ischemia / Q000097:blood* / Q000188:drug therapy; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D010959:Tissue Plasminogen Activator / Q000097:blood*
D004232:Diuretics; D008074:Lipoproteins; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator; D003894:Deamino Arginine Vasopressin