Enzymatic evidence of impaired reperfusion in diabetic patients after thrombolytic therapy for acute myocardial infarction: a role for plasminogen activator inhibitor? (original) (raw)

infarction and has been shown to reduce Objective-To compare the activity of mortality' 2 and improve left ventricular funcplasminogen activator inhibitor (PAI-1) tion.3 However, not all patients treated wvch in diabetic and non-diabetic patients thrombolytic therapy have successful reperfuadmitted with acute myocardial-infarc-sion of the thrombosed artery and therapy is tion and to determine whether PAI-i further limited by reocclusion and reinfarcactivity influences reperfusion after tion in 10-25% of patients.4 The reasons for thrombolytic therapy. the resistance to lysis and the occurrence of Design-Prospective study of patients reocclusion are unclear. Factors such as admitted with acute myocardial infircplatelet activation associated with thrombolytion. SiS,56 and the procoagulant effects of plasmin7 Setting-District general hospital. probably contribute. In addition recent evi-Main outcome measures-Reperfusion dence suggests that the fibrinolytic system, assessed by time to peak release of crea-and in particular plasminogen activator tine kinase-MB isoenzyme. inhibitor (PAI-I), may be important. Both Results-Baseline PAI-1 activity and Sane et al8 and Barbash et a19 showed a relaantigen concentrations were significantly tion between raised PAI-activity on admishigher in diabetic patients (n = 45) than sion with acute myocardial infarction and in non-diabetic patients (n = 110) (24-6 reduced likelihood of a patent infarct related (6.9) v 18'6 (7.9) AU/ml (AU = arbitrar artery after thrombolytic therapy with recomunits) (p = 0-0001) and 58*8 (13.1-328-8) v binant tissue plasminogen activator. 41'0 (10.9-125.4) nglml (p = 0.004). Time Increased activity of PAI-1 has also been to peak release of creatine kinase-MB shown to predict the recurrence of infarction was calculated in 123 (80Yo)-patients. In in young survivors of myocardial infarction.'0 98 who received thrombolytic therapy the In diabetic patients mortality and morbidmedian time to peak enzyme release was ity from acute myocardial infarction are 15.5 h (7.5-24 h) in diabetic patients (n high."' 12 Non-insulin-dependent diabetic = 26) and 12 h (5-26 h) in non-diabetic patients have previously been reported to patients (n = 72) (p = 0.005). In those have increased PM-i activity,"3'4 which may with a time to peak release of A 12 h, play a part in determining the outcome from indicating likely successful reperfusion, myocardial infarction. PAI-1 activity was 17-5 (7 8) AU/ml com-We studied admission levels of PAI-I pared with 228 :(7:7) AU/ml in those with activity and outcome from thrombolytic thera dme to peak release of->12 h-(p = apy for acute myocardial infarction in 155 0001).-In multiple regression analysis patients, both diabetic and non-diabetic, both diabetes :(p = 0.0001) and PAI-i admitted to a district general hospital. The activity at admission (p = 0.029) were aims of this study were to determnme whether independently related to successfil (a) PAI-I activity influences the response to reperfusion. In 13 patients with evidence thrombolytic therapy and (b) whether PAI-i of reinfarction in hospital PAM-i activity activity is higher in diabetic patients with on day 3 was 26*7 (6.4) AU/ml compared acute myocardial infarction than in non-diawith 21*7 :(6.3) AU/ml in those without betic patients-a factor that might influence evidence of reinfrction (p = 0.032). the outcome of thrombolytic therapy in Department of Conclusion-Both raised PAI-i activity diabetic patients. Medicine, University on admission and diabetes were associ-College London Medical Sol, ated withadured likelihood of enzy-Whittington Hospital, matic £vidOceitc of reperfision after Patients and methods London thrombolytic therapy.;.:Increased PAM-1 Over a two year period we studied 155 activity on day-3 was associated with an patients admitted witi acute myocardial Department of increased risk of reinfction. Diabetic-infarction to the Whittington Hospital. They Cardiology, Whittiuaton Hospital. patients had-higher PMI-i activity on-accounted for 60% of all admissions with Londbn admission., Ths may partly explain their acute myocardial infarction over the period. D L P §UC27SO1-reduced likelihood of reperfusion. Patients were excluded if an initial blood Correspondence to: sample was not obtained before the adminis-Dr RP-Oray; Deparent of sp o Cardi&Mogy,VWhittington (Br HeartJ 1993;70:530-536) tration of thrombolytic therapy, if they pre-HosOgtal, HighgateHill, sented more than 24 hours after the onset of London Nf9 5N.. Thrombolytic therapy is now the treatment of chest pamin,-or if myocardial infarction was not Accepted for publication choice for paents with acute myocardial confirmed by World Health Organisation