Increased serum creatine kinase is a reliable marker for acute transplanted heart rejection diagnosis in rats

Abstract

Different molecules have been studied as biochemical markers in heart transplantation. However, their utility is under discussion as results in human and animal models are controversial. In this work, lactate dehydrogenase (LDH), creatine kinase (CK) and cardiac troponin I (TnI) were studied as serologic markers of acute rejection after heterotopical heart transplantation in rats. In predictable rejection experiments, animals were divided into three groups: nonoperated (Lewis rats), control group (Lewis-Lewis isografts) and rejection group (Brown Norway-Lewis allografts). Nonpredictable rejection experiments were performed using nonconsanguineous Sprague-Dawley allografts. In predictable rejection experiments, LDH activity was similar between control and rejection groups. TnI values were heterogeneous in control and rejection groups. In contrast, the rejection group showed CK activity increased 4.5-fold compared with the control group. In addition to these predictable studies, we also presented novel nonpredictable experiments in which rats were divided into groups based on low and high CK activity. Histologic studies in these rats showed that none of those with low CK activity presented rejection signs, while all animals with high CK levels showed grade 2R rejection. These results suggest that CK might be an excellent marker for prediction of rejection in heart transplantation.