The Expression And Clinical Significance Of Arginine-NO Metabolites And MPO In Anthracycline-Induced Cardiotoxicity

Objective:Dynamic monitoring of plasma levels of arginine,asymmetric dimethylarginine(ADMA),citrulline and myeloperoxidase(MPO)in patients with hematological malignancies before and after chemotherapy with anthracyclines,and simultaneously cardiac troponin T(cTnT),myocardial enzymes(LDH,CK,CK-Mb),surface electrocardiogram(ECG)and echocardiography were compared for evaluation Clinical value of arginine,ADMA,citrulline and MPO in early diagnosis of anthracycline-induced cardiac toxicity.Left ventricular fractional shorteningMethods:From November 2018 to November 2019,25 patients with hematological malignancies who received anthracycline treatment in the Department of Hematology,Affiliated Hospital of Chengde Medical University were studied.All selected patients were tested for arginine,ADMA,citrulline,and circulating MPO plasma levels by ELISA before and after chemotherapy.At the same time,cTnT,myocardial enzymes(LDH,CK,CK MB),ECG,LVEF and LVFS were tested by the Affiliated Hospital of Chengde Medical University.The indexes of three months(T1)and six months(T2)of anthracycline exposure were compared and comprehensively analyzed with those of before treatment(T0).Results:1 In this study,25 patients with primary hematological malignancies diagnosed in the Affiliated Hospital of Chengde Medical University and receiving standardized anthracycline chemotherapy were selected,aged 12-80 years,with a median age of 51 years.Among them,acute myeloid leukemia was the main diagnosis(n = 14,56%),followed by lymphoma(n = 8,32%)and multiple myeloma(n = 3,12%).There were 8 patients(32%)with smoking history and 5 patients(20%)with hypertension history.2 The results of echocardiography showed that LVEF and and LVFS before anthracycline chemotherapy,3 months and 6 months of exposure were61.16±4.32% and 32.76±3.26%,61.40±4.35% and 32.92±3.17%,61.00±4.03 % And 32.92 ± 2.92%,and the changes of LVEF and LVFS within 6months of anthracycline exposure were not statistically different from those before chemotherapy(p>0.05).3 The results of body surface ECG showed that QTc intervals before anthracycline chemotherapy,3 months exposure,and 6 months exposure were429± 16.82 ms,437± 22.27 ms,and 444.20 ± 24.14 ms respectively,and the abnormal rate of ECG was 20%,40% and 56% respectively,and the prolonged QTc interval and the abnormal rate of ECG were statistically significant(p<0.05).4 cTnT was 0.05±0.03mg/L,0.07±0.05mg/L and 0.07±0.05mg/L before anthracycline chemotherapy,3 months and 6 months exposure,and LDH was449.56±269.83U/L,494.76±113.66U/L and 547.16±187.42U/L,CK was43.32±25.35U/L,40.40±15.42U/L and 43.24±21.93U/L,CK-MB was10.52±3.76U/L,9.48±4.00U/L and 7.80±3.03U/L.cTnT was not statistically significant within 6 months of exposure to anthracycline compared with before chemotherapy(p>0.05).Only CK-Mb in myocardial enzymes decreased statistically when exposed to anthracycline for 6 months compared with before administration Significance(p<0.01),but no clinical significance.5 Plasma arginine,ADMA,citrulline and MPO were not correlated with age,LDL and BMI,respectively(p>0.05).Arginine was 290.08±61.53ng/ml,281.54±51.06ng/ml and 234.85±25.06ng/ml before anthracycline chemotherapy,3 months and 6 months exposure,ADMA was 0.89±0.16umol/l,1.05±0.21umol/l and 1.00±0.14umol/l,citrulline is 185.49±35.35umol/l,133.24±17.85umol/l and 119.95±18.78umol/l,MPO is 77.69±6.27 respectively ng/ml,91.69±10.09ng/ml and 102.01±18.23ng/ml.And within 6 months of exposure to anthracycline drugs,with the prolongation of exposure time,theplasma levels of ADMA and MPO increased compared with before administration(p<0.05),and the plasma levels of citrulline decreased significantly before administration(p<0.01);the plasma level of arginine was not statistically significant at 3 months of exposure(p>0.05),and significantly decreased at 6 months of exposure(p<0.01).Conclusion:1 The body surface ECG,as a commonly used clinical method for discovering heart disease,showed significant abnormal changes in ECG when anthracyclines were exposed for 6 months.2 The arginine,ADMA,citrulline and MPO changed significantly within6 months after receiving anthracycline chemotherapy,and it is expected to become a new early biomarker of anthracycline-induced to anthracycline chemotherapy.