目的 了解心脏移植术后患者环孢素(CsA)血药浓度变化和排斥反应、不良反应发生情况,并探讨其相关性.方法 收集2010年1月至2011年12月在北京安贞医院行心脏移植术患者的病历资料进行回顾性分析,记录患者的一般情况、CsA血药浓度监测情况以及排斥反应和不良反应发生情况,分析CsA全血谷浓度(C0)和峰浓度(C2)与排斥反应和不良反应的关系. 结果 纳入分析的27例患者中男性24例,女性3例,平均年龄(38±14)岁,平均身高(170±10) cm,平均体重(68.0±15.8) kg.原发疾病:扩张性心脏病18例,冠状动脉粥样硬化性心脏病4例,瓣膜性心肌病3例,心律失常性右心室心肌病1例,心肌致密化不全1例.术后早期(＜1个月)CsA 血药浓度较低,75例次C0检测中35例次(46.7％)、69例次C2检测中56例次(81.2％)低于有效浓度.C0在术后1～3个月升高,4个月后逐渐降低,7个月后逐渐趋于稳定.C2在术后1～3个月升高,4个月后逐渐降低,13个月后略有回升.27例患者中有9例(33.3％)发生排斥反应,8例为急性排斥反应,发生在术后4 ～12个月,主要表现为乏力、食欲不振、活动后心悸、烦躁,其中1例死亡；1例为慢性排斥反应,发生在术后13个月,表现为心率增快和外周血淋巴细胞计数升高.27例中有7例(25.9％)出现肾功能损伤,发生在术后1个月内、3～6个月和7 ～ 12个月者分别为3、2、2例,主要表现为肌酐清除率下降,血清尿素、肌酐、钾升高和高尿酸血症；1例(3.7％)在术后2个月出现肝功能损伤,主要表现为丙氨酸转氨酶(ALT)和总胆红素(TBil)升高；18例(66.7％)出现总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和三酰甘油(TG)升高,发生在术后3个月内和7 ～ 12个月者分别为17和1例；10例(37.0％)出现空腹血糖升高,发生在术后1个月内、4 ～12个月和18个月者分别为7、2和1例.未出现急性排斥反应者CsA的C0及C2均明显高于出现急性排斥反应者[(216±90)μg/L比(167±103)μg/L,(718 ±297) ng/ml比(472 ±251) μg/L,均P＜0.01].出现不良反应者C0及C2均明显高于未出现不良反应者[(241±93)μg/L比(190 ±95) μg/L,(837 ±314) μg/L比(596±283) μg/L,均P＜0.01].CsA的C0与血清尿素、肌酐和空腹血糖相关(r=0.359,P=0.000;r =0.170,P=0.014; r=0.164,P=0.018),C0与C2均与TBil、TC和LDL-C相关(r=0.182,P=0.009; r=-0.170,P=0.018; r=0.267,P=0.001;r =0.320,P =0.000;r =0.251,P=0.001；r=0.275,P=0.000). 结论 心脏移植术后患者CsA血药浓度与排斥反应和不良反应的发生密切相关,进行CsA血药浓度监测有利于及时调整CsA剂量,降低排斥反应和不良反应发生率.
目的 瞭解心髒移植術後患者環孢素(CsA)血藥濃度變化和排斥反應、不良反應髮生情況,併探討其相關性.方法 收集2010年1月至2011年12月在北京安貞醫院行心髒移植術患者的病歷資料進行迴顧性分析,記錄患者的一般情況、CsA血藥濃度鑑測情況以及排斥反應和不良反應髮生情況,分析CsA全血穀濃度(C0)和峰濃度(C2)與排斥反應和不良反應的關繫. 結果 納入分析的27例患者中男性24例,女性3例,平均年齡(38±14)歲,平均身高(170±10) cm,平均體重(68.0±15.8) kg.原髮疾病:擴張性心髒病18例,冠狀動脈粥樣硬化性心髒病4例,瓣膜性心肌病3例,心律失常性右心室心肌病1例,心肌緻密化不全1例.術後早期(＜1箇月)CsA 血藥濃度較低,75例次C0檢測中35例次(46.7％)、69例次C2檢測中56例次(81.2％)低于有效濃度.C0在術後1～3箇月升高,4箇月後逐漸降低,7箇月後逐漸趨于穩定.C2在術後1～3箇月升高,4箇月後逐漸降低,13箇月後略有迴升.27例患者中有9例(33.3％)髮生排斥反應,8例為急性排斥反應,髮生在術後4 ～12箇月,主要錶現為乏力、食欲不振、活動後心悸、煩躁,其中1例死亡；1例為慢性排斥反應,髮生在術後13箇月,錶現為心率增快和外週血淋巴細胞計數升高.27例中有7例(25.9％)齣現腎功能損傷,髮生在術後1箇月內、3～6箇月和7 ～ 12箇月者分彆為3、2、2例,主要錶現為肌酐清除率下降,血清尿素、肌酐、鉀升高和高尿痠血癥；1例(3.7％)在術後2箇月齣現肝功能損傷,主要錶現為丙氨痠轉氨酶(ALT)和總膽紅素(TBil)升高；18例(66.7％)齣現總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)和三酰甘油(TG)升高,髮生在術後3箇月內和7 ～ 12箇月者分彆為17和1例；10例(37.0％)齣現空腹血糖升高,髮生在術後1箇月內、4 ～12箇月和18箇月者分彆為7、2和1例.未齣現急性排斥反應者CsA的C0及C2均明顯高于齣現急性排斥反應者[(216±90)μg/L比(167±103)μg/L,(718 ±297) ng/ml比(472 ±251) μg/L,均P＜0.01].齣現不良反應者C0及C2均明顯高于未齣現不良反應者[(241±93)μg/L比(190 ±95) μg/L,(837 ±314) μg/L比(596±283) μg/L,均P＜0.01].CsA的C0與血清尿素、肌酐和空腹血糖相關(r=0.359,P=0.000;r =0.170,P=0.014; r=0.164,P=0.018),C0與C2均與TBil、TC和LDL-C相關(r=0.182,P=0.009; r=-0.170,P=0.018; r=0.267,P=0.001;r =0.320,P =0.000;r =0.251,P=0.001；r=0.275,P=0.000). 結論 心髒移植術後患者CsA血藥濃度與排斥反應和不良反應的髮生密切相關,進行CsA血藥濃度鑑測有利于及時調整CsA劑量,降低排斥反應和不良反應髮生率.
목적 료해심장이식술후환자배포소(CsA)혈약농도변화화배척반응、불량반응발생정황,병탐토기상관성.방법 수집2010년1월지2011년12월재북경안정의원행심장이식술환자적병력자료진행회고성분석,기록환자적일반정황、CsA혈약농도감측정황이급배척반응화불량반응발생정황,분석CsA전혈곡농도(C0)화봉농도(C2)여배척반응화불량반응적관계. 결과 납입분석적27례환자중남성24례,녀성3례,평균년령(38±14)세,평균신고(170±10) cm,평균체중(68.0±15.8) kg.원발질병:확장성심장병18례,관상동맥죽양경화성심장병4례,판막성심기병3례,심률실상성우심실심기병1례,심기치밀화불전1례.술후조기(＜1개월)CsA 혈약농도교저,75례차C0검측중35례차(46.7％)、69례차C2검측중56례차(81.2％)저우유효농도.C0재술후1～3개월승고,4개월후축점강저,7개월후축점추우은정.C2재술후1～3개월승고,4개월후축점강저,13개월후략유회승.27례환자중유9례(33.3％)발생배척반응,8례위급성배척반응,발생재술후4 ～12개월,주요표현위핍력、식욕불진、활동후심계、번조,기중1례사망；1례위만성배척반응,발생재술후13개월,표현위심솔증쾌화외주혈림파세포계수승고.27례중유7례(25.9％)출현신공능손상,발생재술후1개월내、3～6개월화7 ～ 12개월자분별위3、2、2례,주요표현위기항청제솔하강,혈청뇨소、기항、갑승고화고뇨산혈증；1례(3.7％)재술후2개월출현간공능손상,주요표현위병안산전안매(ALT)화총담홍소(TBil)승고；18례(66.7％)출현총담고순(TC)、저밀도지단백담고순(LDL-C)화삼선감유(TG)승고,발생재술후3개월내화7 ～ 12개월자분별위17화1례；10례(37.0％)출현공복혈당승고,발생재술후1개월내、4 ～12개월화18개월자분별위7、2화1례.미출현급성배척반응자CsA적C0급C2균명현고우출현급성배척반응자[(216±90)μg/L비(167±103)μg/L,(718 ±297) ng/ml비(472 ±251) μg/L,균P＜0.01].출현불량반응자C0급C2균명현고우미출현불량반응자[(241±93)μg/L비(190 ±95) μg/L,(837 ±314) μg/L비(596±283) μg/L,균P＜0.01].CsA적C0여혈청뇨소、기항화공복혈당상관(r=0.359,P=0.000;r =0.170,P=0.014; r=0.164,P=0.018),C0여C2균여TBil、TC화LDL-C상관(r=0.182,P=0.009; r=-0.170,P=0.018; r=0.267,P=0.001;r =0.320,P =0.000;r =0.251,P=0.001；r=0.275,P=0.000). 결론 심장이식술후환자CsA혈약농도여배척반응화불량반응적발생밀절상관,진행CsA혈약농도감측유리우급시조정CsA제량,강저배척반응화불량반응발생솔.
Objective To understand the changes in cyclosporine A (CsA) blood concentration,the occurrence of rejection and adverse reactions in patients after heart transplantation (HT),and to explore their correlations.Methods The clinical data of patients who underwent HT in Beijing Anzhen Hospital from January 2010 to December 2011 were collected and analyzed retrospectively.The patients'general condition,monitoring situation of CsA blood concentration,as well as the occurrence of rejection and adverse reactions were recorded.The relationship between CsA trough concentration (C0),peak concentration (C2),and rejection,adverse reactions were analyzed.Results Twenty-seven patients were enrolled in the analysis.They comprised 24 males and 3 females with a mean age of (38 ± 14) years,a mean hcight of (170 ± 10) cm,a mean body weight of (68.0± 15.8) kg.Primary diseases included 18 cases with dilated heart disease,4 cases with coronary atherosclerotic cardiopathy,3 cases with valvular cardiomyopathy,one case with arrhythmogenic right ventricular cardiomyopathy,and one case with noncompaction of ventricular myocardium.The CsA blood concentration was low in early postoperative phase(＜ 1 month).Of the 75 C0 tests,the levels of C0 in 35 tests (46.7％) were below the range of effective concentration.Of the 69 C2 tests,the levels of C0 in 56 tests (81.2％) were below the range of effective concentration.C0 increased from 1 to 3 months after HT,decreased gradually 4 months after HT,and tended to be stable 7 months after HT.C2 increased from 1 to 3 months after HT,decreased gradually 4 months after HT,and increased slightly 13 months after HT.Rejection occurred in 9 of the 27 patients (33.3％),in 8 cases acute rejection occurred 4 to 12 months after HT.The main clinical manifestations were fatigue,loss of appetite,and palpitation after exercise and irritability.One patient died.In one case chronic rejection occurred 13 months after HT,the clinical manifestations included increased heart rate and peripheral blood lymphocyte count.Seven of the 27 patients (25.9％) developed renal injury.The main clinical manifestations were decline in creatinine clearance,rise in serum urea,creatinine and potassium,and hyperuricemia.The renal injury occurred in 3,2,and 2 patients within 1 month,3 to 6 months and 7 to 12 months after HT,respectively.One patient (3.7％) developed liver injury 2 months after HT,the clinical manifestations were increased levels of alanine aminotransferase (ALT) and total bilirubin (TBil).The levels of total cholesterol,LDL-cholesterol,and triglycerides increased in 18 patients (66.7％),occurred in 17 and 1 patients within 3 months and 7 to 12 months after HT,respectively.The levels of fasting plasma glucose increased in 10 patients (37.0％) and occurred in 7,2 and 1 patients within one month,4 to 12 months,and 18 months after HT,respectively.C0 and C2 in patients with non-rejection were significantly higher than those with acute rejection [(216 ±90) μg/L vs.(167 ± 103) μg/L,(718 ±297) μg/L vs.(472 ±251) μg/L,all P ＜0.01].C0 and C2 in patients with adverse reactions were significantly higher than those without adverse reactions [(241 ± 93) μg/L vs.(190 ± 95) μg/L,(837 ±314) μg/L vs.(596 ±283) μg/L,all P ＜0.01].C0 was related to the blood serum urea,the creatinine,and the fasting plasma glucose (r =0.359,P =0.000 ; r =0.170,P =0.014 ; r =0.164,P =0.018).C0 and C2 were related to the TBil,TC,and LDL-C (r =0.182,P =0.009; r =-0.170,P =0.018; r =0.267,P =0.001; r=0.320,P=0.000; r=0.251,P=0.001; r=0.275,P=0.000).Conclusions The CsA blood concentration in patient after HT is closely related to the occurrence of rejection and adverse reactions.Monitoring of CsA blood concentration is helpful to adjust the dose of CsA timely in order to reduce the incidence of rejection and adverse reactions.
