Research On Arginine-NO Metabolites And MPO In Acute Cardiotoxicity Of Anthracyclines

Objective:For patients with new hematological malignancies exposed to anthracyclines for the first time,collect relevant clinical data: including highly sensitive troponin I(TNHS),NT-Pro BNP,myocardial enzymes(LDH,CK,CK-Mb),liver Function(TBIL,DBIL,IBIL,ALT,AST,γ-GT),renal function(CRE,BUN),electrocardiogram.Simultaneously detect the changes in plasma levels of myeloperoxidase(MPO),arginine,citrulline,and asymmetric dimethylarginine(ADMA)before and within 24 hours after chemotherapy,and evaluate its clinical value to early distinguish acute cardiotoxicity of anthracyclines.Methods:Included 25 patients with first-onset hematological malignancies from September 2020 to December 2020 in the Department of Hematology of the Chengde Affiliated Hospital,who were exposed to anthracyclines for the first time.The laboratory department completed TNHS,NT-Pro BNP,myocardial enzymes(CK,CK-Mb,LDH),renal function(CRE,BUN),liver function(TBIL,DBIL,IBIL,ALT,AST)and ECG indicator detection.At the same time,the plasma levels of arginine,citrulline,ADMA and MPO were detected by ELISA on the specimens of the study subjects before chemotherapy and within 24 hours after chemotherapy.Comprehensive analysis of the changes of each index level before anthracycline chemotherapy(T0)and within 24 hours of anthracycline exposure(T1).Count data is described by composition ratio or rate(%),measurement data shall be tested for normality,measurement data conforming to normal distribution shall be described by mean±standard deviation(X ±s),The measurement data of non-normal distribution is described by M(Q1,Q3).The comparison between groups was performed by χ~2 test,paired t-test and Wilcoxon signed-test for statistical analysis.The difference is statistically significant with p value <0.05(two-sided test).Results:1 The clinical data of 25 patients with first-onset hematological malignancies who were exposed to anthracycline chemotherapy for the first time were collected.The median age of the subjects was 47 years old.The main diagnosis is acute myeloid leukemia(n=16,64%),followed by lymphoma(n=5,20%),acute lymphoblastic leukemia(n=2,8%),multiple myeloma(n= 1,4%),myelodysplastic syndrome(n=1,4%).Among them,3patients had a history of hypertension,accounting for 12%;6 patients had a history of smoking,accounting for 24%.2 The electrocardiogram showed that the abnormal rate of ECG before and within 24 hours of chemotherapy with anthracyclines were 28% and 76%respectively,and the QTc intervals were 426.24±19.17 ms and440.60±24.62 ms respectively.The ECG abnormalities and QTc interval prolongation before chemotherapy and within 24 hours of exposure are statistically significant(p<0.05).3 The positive rates of TNHS before anthracycline chemotherapy and within 24 hours of chemotherapy were 8% and 12% respectively,and NT-Pro BNP was 392.72±144.19pg/ml,441.20±151.45pg/ml,and CK was61.81±39.99U/L,50.59±41.20U/L,CK-MB was 7.70±3.67,9.13±4.38,LDH was 510.04±205.04U/L,451.52±224.84U/L,TNHS,NT-Pro BNP,Myocardial enzymes were not statistically significant before and within 24 hours after chemotherapy of anthracyclines(p>0.05).4 CRE before anthracycline chemotherapy and within 24 hours of chemotherapy were 57.01±14.83umol/L,55.6±13.93umol/L,BUN was5.52±1.64mmol/L,5.61±2.19mmol/L,CRE and BUN were not statistically significant within 24 hours of exposure to anthracyclines than before treatment(p>0.05).5 TBIL before anthracycline chemotherapy and within 24 hours of chemotherapy were 12.07±3.75umol/L,13.17±4.75umol/L respectively,DBIL was 1.69±1.99umol/L,1.96±2.06umol/L,IBIL was 8.92±5.05umol/L,9.81±5.32umol/L,ALT was 30.40±10.85U/L,27.84±10.03U/L,AST was25.62±7.39U/L,24.8±6.42 U/L,and γ-GT was 30.74±10.98,27.86±8.51 U/L respectively.TBIL,DBIL,IBIL,ALT,AST,γ-GT were not statistically significant within 24 hours of exposure to anthracyclines than before chemotherapy(p>0.05).6 Comprehensive analysis of the correlation between plasma myeloperoxidase,arginine,citrulline,ADMA and age,body mass index and other indicators of the enrolled patients,the result is no correlation respectively(p>0.05).Arginine before anthracycline chemotherapy and within24 hours of chemotherapy were respectively 291.88±26.41ng/ml,290.99±37.61ng/ml,ADMA was 16.89(14.01,37.10)ng/ml,28.96(19.24,48.18)ng/ml,citrullin was 180.26±34.14umol/l,170.89±34.46umol/l,and MPO was 78.65±50.50ng/ml,110.16±62.68ng/ml respectively.The changes of arginine was not statistically significant within 24 hours of exposure to anthracyclines than before treatment(p>0.05);the plasma levels of myeloperoxidase and asymmetric dimethylarginine increased within 24 hours of chemotherapy than before treatment(p<0.05);plasma citrulline decreased compared with before treatment(p < 0.05),the difference is statistically significantConclusion:1 The body surface ECG,as a commonly used clinical method for discovering heart disease,and has clinical value for early detection of heart damage.2 ADMA,citrulline and MPO changed significantly within 24 hours of exposure anthracycline chemotherapy,which can detect acute cardiotoxicity of anthracycline earlier.