Influence of Cardiac Output on Peak t-PA Plasma Levels in Patients Receiving Thrombolytic Therapy with Recombinant Tissue-Type Plasminogen Activator – Correlation with Patency Rate

Summary

We studied 35 consecutive patients with short onset of myocardial infarction who underwent thrombolytic therapy with rt-PA at a standard dosage regimen of 100 mg rt-PA total (10 mg given as a bolus followed by 50 mg, 20 mg and 20 mg per hour for 3 hours). These patients were monitored for t-PA antigen and t-PA activity and PAI-1 activity plasma levels during rt-PA infusion. Success or failure of thrombolytic therapy was evaluated by non-invasive criteria (early plasma creatine kinase peaks, early peak plasma myoglobin values, and electrocardiographic criteria) as well as by means of coronary angiography at the fourth day after thrombolytic treatment. In 24 (68.6%) of these patients a success of thrombolytic therapy could be established by these criteria, while 11 patients did not respond to thrombolytic therapy. Fifteen patients (14 responders and one non-responder) had to be excluded from the further evaluation because in these patients clinical laboratory data obtained upon admission before initiation of thrombolytic therapy were not complete. Therefore, 20 patients (10 responders and 10 non-responders) could further be analysed. The two groups of patients were not significantly different in body weight, body weight index, age, gender, liver or kidney functional parameters as determined before initiation of the thrombolytic therapy. Furthermore, PAI-1 plasma levels before initiation of thrombolytic therapy were not significantly different in the two groups, as were rt-PA dosage per body weight or body weight index. Only heart rate and calculated cardiac output and cardiac index were significantly higher in the group of patients not responsive to thrombolytic therapy. t-PA values, however, at 30, 60 and 90 min after initiation of rt-PA infusion were significantly higher in the group of responders as compared to the group of non-responders. From these data we conclude that cardiac output which in turn determines liver blood flow might lead to different t-PA plasma levels following the same rt-PA dosage and the resulting t-PA plasma level might determine success or failure of thrombolytic therapy in respect to reopening of the infarct-related vessel.

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