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(Circulation. 2004;109:2398-2400.)
© 2004 American Heart Association, Inc.
Brief Rapid Communications |
From the Third Department of Internal Medicine (Y.K., M.Y., K.A., T.K., N.M., K.M., I.M.), Department of Emergency Medicine (H.T.), and Department of Biology (T.Y.), Faculty of Medical Sciences, University of Fukui, Fukui; Division of Cardiology (H.T., S.I., H.H., S.O., K.T.), Gunma Prefecture Cardiovascular Center, Gunma; and Department of Legal Medicine (K.K.), Gunma University Graduate School of Medicine, Gunma, Japan.
Correspondence to Toshihiro Yasuda, PhD, Department of Biology, Faculty of Medical Sciences, University of Fukui, Fukui 910-1193, Japan. E-mail tyasuda{at}fmsrsa.fukui-med.ac.jp
Received November 15, 2003; de novo received February 13, 2004; revision received April 8, 2004; accepted April 9, 2004.
| Abstract |
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Methods and Results Serum samples were collected from the patients with AMI, unstable angina pectoris, stable angina pectoris, and other diseases. Levels of serum deoxyribonuclease I (DNase I) activity in the patients were determined. An abrupt elevation of serum DNase I activity was observed within approximately 3 hours of the onset of symptoms in patients with AMI, with significantly higher activity levels (21.7±5.10 U/L) in this group compared with the other groups with unstable angina pectoris (10.4±4.41 U/L), angina pectoris (10.8±3.70 U/L), and other diseases (9.22±4.16 U/L). Levels of the DNase I activity in serum then exhibited a marked time-dependent decline within 12 hours and had returned to basal levels within 24 hours.
Conclusions We suggest that serum DNase I activity could be used as a new diagnostic marker for the early detection of AMI.
Key Words: myocardial infarction enzymes diagnosis
| Introduction |
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Deoxyribonuclease I (DNase I, EC 3.1.21.1), one of the well-known enzymes, was the first enzyme to be recognized as specific for DNA.4 One of its proposed roles is DNA breakdown during apoptosis.5 DNase I has been detected in human myocardium, and it has been reported that the activity level increases in heart failure due to idiopathic dilated cardiomyopathy.6 However, the association between serum DNase I activity level and coronary heart disease (CHD) has not yet been clarified. In the present study, we assessed the serum DNase I activity in patients with AMI and related CHD and found that there is a specific elevation of serum DNase I activity in the very early stages of AMI.
| Methods |
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The human ethics committees within the study institutes approved this study protocol, and all patients gave written informed consent.
Biochemical Assessment
The level of the DNase I activity in serum samples was determined using the single radial enzyme diffusion method, as described previously.8,9 Serum creatine kinase isoenzyme MB (CK-MB) and troponin T concentrations were determined using conventional methods. In this study, the cutoff levels for concentration of CK-MB and troponin T were 5.20 and 0.01 µg/L, respectively.
Statistical Analysis
Data were expressed as mean±SD. Statistical comparison between patient groups was performed by ANOVA using StatView software. Differences were considered significant at P<0.05.
| Results |
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In 18 patients with AMI admitted to our hospitals within 3 hours of the onset of chest pain, the mean serum DNase I activity level was significantly higher than that found in the UAP, AP, or OD group (Table and Figure, C); levels of the activity in the patients with AHF, CHF, CRF, stroke, and trauma were 7.91±3.31, 10.0±4.10, 8.00±3.75, 10.9±3.70, and 7.41±3.50 U/L, respectively. Furthermore, the serum DNase I activity level (8.50±2.80 U/L) in the 9 patients with CPS who were initially considered to have AMI on clinical grounds but found to have no evidence of myocardial infarction on follow-up assessment was within the normal range. Therefore, this elevation in the serum activity level seems to be specific for AMI when compared with other forms of CHD in which onset of acute chest pain is a feature.
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When we examined the relationship between serum DNase I activity level in the AMI group and the time delay between symptom onset and hospital admission, the mean serum DNase I activity subsided over time and reached basal levels within 24 hours; the mean value between 0 and 3 hours was 21.7±5.10 U/L (n=18); between 3 and 6 hours was 14.1±2.50 U/L (n=15); between 6 and 12 hours was 10.5±4.20 U/L (n=11); and between 12 and 24 hours was 8.30±2.10 U/L (n=9). This relationship reflected the intra-individual time-dependent changes in the serum DNase I activity seen in all patients in the AMI group after hospital admission. The serum levels of DNase I activity exceeded the cutoff levels in 88% of the patients. By contrast, in the 18 patients with AMI admitted within 3 hours of onset, only 8 were CK-MBpositive and 9 were troponin Tpositive on admission. Thus, we were able to detect an elevation in the serum DNase I activity within approximately 3 hours of the onset of symptoms and before accurate CK-MB and troponin T results.
| Discussion |
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Serum DNase I activity was significantly elevated within 3 hours of the onset of acute chest pain in the patients with AMI, whereas the serum levels of CK-MB and troponin T were slightly elevated and exceeded the cutoff levels in approximately 45% of those patients; we were thus able to detect the elevation of the serum DNase I activity earlier than that of CK-MB and troponin T. As an early marker for myocardial necrosis, the serum myoglobin level is a sensitive test but lacks cardiac specificity, because there may be an elevation in the serum levels of myoglobin secondary to musculoskeletal injury.13 However, the serum DNase I activity level does not rise after trauma, and surgical trauma has been reported to induce no elevation of the activity,14 suggesting that DNase I may be a more specific marker for AMI than myoglobin. Furthermore, there is a slight overlap between the levels of activity in patients with AMI and patients with OD (Figure, C). Because the latter patients do not suffer from chest pain, this overlap would not lower the diagnostic accuracy of serum DNase I activity testing. Thus, the serum DNase I level may be a useful clinical tool in the early diagnosis of AMI within approximately 3 hours of the onset of symptoms.
The results of the present study will facilitate future studies in larger numbers of patients to evaluate the enzyme as a useful biochemical marker with regard to specificity and sensitivity in comparison with the other cardiac markers, such as myoglobin and heart-type fatty-acid binding protein.15
| Acknowledgments |
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| References |
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