Continuous 48-h C1-inhibitor treatment, following reperfusion therapy, in patients with acute myocardial infarction.

AIMS: Complement inhibition by C1-inhibitor has been shown to reduce myocardial ischaemia-reperfusion injury in animal models. We therefore studied the effects of intravenous C1-inhibitor, following reperfusion therapy, in patients with acute myocardial infarction. METHODS AND RESULTS: C1-inhibitor therapy was started not earlier than 6h after acute myocardial infarction, in order to prevent interference with thrombolytic therapy. A loading dose of C1-inhibitor was followed by a continuous infusion for 48 h, using three escalating dosage schemes. Efficacy of complement inhibition was estimated from C4 activation fragments. Plasma concentrations of myocardial proteins were compared to values measured in matched control patients. In 22 patients, C1-inhibitor was well tolerated and drug-related adverse events were not observed. Target plasma levels of C1-inhibitor were reached, with values of 48.2 ml.kg(-1) for distribution space and 35.5h for the half-life time of C1-inhibitor. A dose-dependent reduction of C4 fragments was found P=0.005). In 13 patients who received early thrombolytic therapy, release of troponin T and creatine kinase-MB(mass) was reduced by 36% and 57%P =0.001), compared to 18 controls. CONCLUSION: Continuous 48-h treatment with C1-inhibitor provides safe and effective inhibition of complement activation after reperfused acute myocardial infarction and may reduce myocardial injury.

Effect of acute phase response on cumulative troponin T release.

UNLABELLED: We studied a possible effect of the extent of the acute phase response after acute myocardial infarction on the cumulative release of troponin T. The height of the acute phase response might influence the cumulative release of troponin T, bound to the myofibrillar structures of the heart, in a different way compared to the free cytoplasmic cardiac marker hydroxybutyrate dehydrogenase (EC 1.1.1.27). To investigate this, the cumulative amount of C-reactive protein in plasma, i.e. the quantified acute phase response, was related to the cumulative plasma release of hydroxybutyrate dehydrogenase (an established method for infarct sizing) on the one hand and to that of troponin T on the other hand. The study was performed in patients receiving (n=16) and in patients not receiving (n=6) thrombolytic therapy. Cumulative protein release was calculated using a two-compartment model for circulating proteins. CONCLUSIONS: The cumulative amount of plasma C-reactive protein is significantly higher in the patients not receiving thrombolytic therapy, as is in accordance with earlier studies. The cumulative amount of troponin T released is significantly related to the cumulated concentration of C-reactive protein, especially in patients not receiving thrombolytic therapy. The intensity of the acute phase response, estimated from cumulative plasma C-reactive protein response, has no effect on the relative proportions of troponin T and hydroxybutyrate dehydrogenase released into plasma.