经冠状动脉自体骨髓单个核细胞移植治疗急性心肌梗死的安全性观察

目的采用随机对照研究方法观察经冠状动脉自体骨髓单个核细胞(BM-MNCs)移植治疗急性心肌梗死(AMI)的安全性。方法入选184例AMI患者,分为细胞移植组92例和对照组92例,两组患者在药物治疗基础上,分别在介入治疗同时,经微导管于梗死相关动脉内支架远端注入自体BM-MNCs悬液或等量的肝素生理盐水(对照组)。记录骨髓收集及分离过程中可能出现的迷走反射(如面色苍白、晕厥、恶心、低血压甚至休克)、心绞痛发作、心力衰竭加重等,细胞悬液输注中可能出现的心律失常(窦性心动过缓、窦性停搏或三度房室传导阻滞、心室颤动)、低血压、栓塞等不良反应。监测术后1周内体温、心率、血压、心肌酶谱变化,并根据预先设定的时间点行24小时动态心电图、血常规、肝肾功能、血糖、血脂、血尿酸、心肌酶谱和高敏C反应蛋白(hs-CRP)检测,定期复查冠状动脉造影和经胸超声心动图。计划随访2年,记录主要心脏事件发生率、支架内再狭窄以及肿瘤等发生情况。结果在骨髓收集和分离过程中患者未出现心绞痛发作、心力衰竭加重等并发症,迷走反射相关不良反应均为一过性。两组患者平均随访(14．5±8．1)个月。与对照组相比,移植组围手术期及随访期间不良事件发生率差异无统计学意义:围手术期(≤1周)4．3％比5．7％(P>0．05);术后3个月为3．5％比2．4％(P>0．05);术后6个月至30个月为11．7％比14．3％(P>0．05)。未发现与移植相关的恶性心律失常、感染、心肌缺血加重、支架内再狭窄增加等。随访期间未发生死亡、新发肿瘤、栓塞等事件。同时,与对照组相比,BM-MNCs移植可以在介入治疗的基础上进一步提高左室射血分数。结论经冠状动脉自体BM-MNCs移植治疗AMI安全可行,且能改善心功能。     

经冠状动脉骨髓单个核细胞移植治疗原发性扩张型心肌病的安全性与疗效近期观察

目的研究经冠状动脉自体骨髓单个核细胞移植治疗原发性扩张型心肌病的安全性以及近期疗效。方法入选18例原发性扩张型心肌病患者,随机分为对照组8例和移植组10例,两组均予常规抗心力衰竭(心衰)药物治疗。移植组接受经冠状动脉自体骨髓单个核细胞移植。两组术前、术后48H、1、3和6个月分别检测血常规及生化指标(肝功能、肾功能、血糖、血脂、血尿酸和HSCRP),术前、术后1、3和6个月分别行超声心动图、动态心电图、6MIN步行试验,术前及术后1、6个月行心脏MRI检查测定心肌损伤面积及左室射血分数。随访至2年,记录患者年住院天数,以死亡作为研究终点。结果细胞移植组术后48H、1、3和6个月血常规及生化指标与对照组和自身术前相比均无显著性差异(P>0.05)。术后6个月,细胞移植组6MIN步行路程增加,明显高于对照组[(494.3±62.8)M比(307.2±75.0)M,P<0.05],也显著高于术前[(494.3±62.8)M比(321.5±63.7)M,P<0.05]。术后6个月超声心动图显示两组间左室舒张末容积和左室射血分数无统计学差异(P>0.05)。MRI测定心脏损伤面积结果发现移植组患者术后(4.96±0.47)CM2较术前(5.12±0.54)CM2及对照组(5.02±0.39)CM2有减少的趋势,但是不具有统计学差别(P>0.05)。两组患者生存率无统计学差异,但移植组患者年平均住院天数明显低于对照组[(30.2±11.2)D比(43.6±9.8)D,P<0.05]。结论经冠状动脉自体骨髓单个核细胞移植治疗原发性扩张型心肌病,可延长6MIN步行路程,降低患者再入院比率,有助于改善心衰症状,且比较安全。     

空腹高血糖的2型糖尿病患者加用甘精胰岛素或中性鱼精蛋白锌胰岛素的比较研究

单用口服降糖药血糖控制不佳的2型糖尿病患者分别加用甘精胰岛素或中性鱼精蛋白锌胰岛素(NPH)联合治疗3个月,然后停止胰岛素治疗,恢复原口服治疗方案,共观察6个月。结果甘精胰岛素组的HbAIC和餐后血糖低于NPH组[治疗3个月(6．1±0．5)％vs(6．9±0．8)％和(7．2±2．1)mmol／L vs(9．3±3．1)mmol／L,治疗6个月(6．6±0．7)％vs(7．4±1．1)％和(8．8±2．8)mmol／Lvs(10．3±3．1) mmoL／L,P<0．01或P<0．05],两指标的下降值甘精胰岛素组大于NPH组[治疗3个月(4．0±0．7)％vs (3．7±0．6)％和(7．1 4-2．0)mmol／Lvs(5．9±1．8)mmol／L,治疗6个月(3．5±0．5)％vs(3．2±0．3)％和(5．5±1．4)mmol／Lvs(4．9±1．3)mmol／L,P<0．01或P<0．05],提示使用甘精胰岛素可以在不增加不良反应的情况下比NPH更加全面而有效地控制血糖。     

经静脉移植自体骨髓单个核细胞治疗猪急性心肌梗死的实验研究

目的探讨静脉内移植自体骨髓单个核细胞(BM-MNCs)治疗猪急性心肌梗死的有效性和安全性。方法静脉内移植BM-MNCs后4周观察移植细胞归巢情况、小血管密度、心功能及冠脉侧支血管形成情况及可能发生的不良反应。结果静脉内MNCs移植后4周心肌细胞间可见少量发蓝色荧光的移植细胞,散在分布,心肌细胞间有较多新生毛细血管并可见新生的心肌样细胞;移植组小血管密度(68.25±9.54)条/mm~2明显高于对照组(35.14±7.06)条/mm~2(P<0.01),左心室射血分数(LVEF,62.75%±5.08%)、短轴缩短率(FS,40.28%±4.73%)也明显高于对照组LVEF(46.34%±5.94%)、FS(29.34%±3.86%)(均为P<0.05);移植组冠脉侧支循环形成较对照组明显;静脉内移植MNCs没有发现异常增生、钙化或肿瘤形成。结论经静脉移植的BM-MNCs可归巢到宿主心肌,有助于促进缺血心肌血管新生,改善左心室收缩功能的作用。     

雷公藤多甙用于1型糖尿病患者的免疫干预治疗

目的观察用雷公藤多甙对1型糖尿病患者进行免疫干预治疗的疗效。方法在均使用胰岛素作为基础治疗的情况下,46例1型糖尿病患者随机分为治疗组(加用雷公藤多甙)及对照组,每组23例。比较入组时和治疗6个月后血糖、血清C肽、胰岛自身抗体水平和T淋巴细胞亚群的变化。结果两组患者入组时血糖控制均较差,治疗后空腹血糖(FBG)及餐后血糖(PBG)以及HbAIC均有显著下降(P< 0．01),但与对照组相比,治疗组降低更明显(P<0．05或P<0．01)。两组治疗后空腹和餐后C肽水平均呈现下降趋势(P<0．05),但治疗组的下降率较小(P<0．01)。入组时两组的胰岛素剂量相似,治疗6个月后雷公藤多甙治疗组所用的胰岛素剂量较对照组少(P<0．01)。治疗前,两组患者存在血清谷氨酸脱羧酶抗体(GADA)、胰岛细胞抗体(ICA)、蛋白酪氨酸磷酸酶抗体(IA-2A)阳性。治疗后对照组抗体水平无变化,治疗组GADA和IA-2A的阳性率及均值水平趋下降(均P<0．05)。治疗组在治疗后外周血CD4+、HLA- DR+T淋巴细胞亚群均值水平降低[(42．3±3．3)％vs(38．4±3．6)％,(21．2±2．6)％vs(16．7±3．1)％,P<0．01],CD8+ T淋巴细胞亚群水平升高[(23．0±2．8)％vs(27．7±2．1)％,P<0．01],而对照组无明显变化。结论雷公藤多甙可在一定程度上减轻1型糖尿病患者自身免疫导致的胰岛β细胞破坏,从而延缓疾病的进程。     

中老年继发孔型房间隔缺损经导管封堵术后左、右心功能变化

目的:探讨中老年继发孔型房间隔缺损(ASD)经导管封堵术后左、右心功能变化。方法:观察269例接受封堵治疗的40岁以上ASD患者术前和术后X线胸片、经胸超声心动图(TTE)和心电图变化。另选择同期30例健康查体的相同年龄和性别构成比对象作为超声指标的正常对照。结果:全组缺损TTE最大径平均17．7±5．3(5～30)mm,选用封堵器直径平均27．5±6．0(13～40)mm。心功能术后1天较术前、术后1个月较术后1天改善,有显著性差异(P<0．05～0．001)。心胸比率术后1天较术前、术后6个月较术后1个月缩小,有显著性差异(P<0．05～0．001)。心电图:右心房高负荷率、RV1+SV5、QRS间期、右束支传导阻滞比率术后1天较术前、术后1个月较术后1天,均有显著性差异(P<0．05～0．001)。超声心动图:右心室前后径,术后1天较术前、术后1个月较术后1天、术后6个月较术后1个月缩小,均有极显著性差异(P<0．01～0．001);主肺动脉内径术后1天较术前缩小,但术后6个月仍高于正常对照,有极显著性差异(P<0．001)。三尖瓣反流程度分级术后1天较术前、术后1个月较术后1天,均有显著性差异(P<0．05～0．001)。左心房前后径术前、术后无显著性变化。左心室舒张末期内径术后1天较术前、术后1个月较术后1天、术后6个月较术后1个月增加,均有极显著性差异(P<0．01～0．001),左心室射血分数术后1天较术前增加,有极显著性差异(P<0．001)。结论:封堵治疗能够有效降低中老年ASD右心内径和肺动脉收缩压,增加左心室内径,改善左心室收缩功能和心室电传导。近中期疗效满意,远期疗效有待于进一步观察。     

经冠脉移植自体骨髓干细胞治疗扩张型心肌病的安全性及疗效

目的：探讨经冠状动脉自体骨髓干细胞移植治疗扩张型心肌病的安全性和疗效。方法：选择经超声、冠状动脉造影证实为扩张型心肌病患者52例，随机分为自体骨髓干细胞移植组（细胞移植组）和对照组，两组均予常规抗心力衰竭（心衰）药物治疗，细胞移植组自体骨髓干细胞经微导管注入左、右冠状动脉。两组术前，术后24h、48h，1、3和6个月分别检测血常规及生化指标（肝功能、肾功能、血糖、血脂、血尿酸、肌酸激酶、肌酸激酶同工酶和hs—CRP），术前，术后1、3和6个月分别行超声心动图、动态心电图、6min步行试验检查。结果：细胞移植组术后24h、48h，1、3和6个月血常规及生化指标与对照组和自身术前相比均无显著性差异（P〉0．05）。术后6个月，细胞移植组6min步行路程增加，与对照组有显著差异（P〈0．05），与术前有显著差异（P〈0．05），但超声心动图显示两组间左室舒张末容积和左室射血分数无统计学差异（P〉0．05）。围手术期及术后6个月随访中未见任何严重心律失常等不良反应发生。结论：经冠状动脉自体骨髓干细胞移植治疗扩张型心肌病安全、有效。     

基因修饰的骨髓基质细胞移植治疗帕金森病模型大鼠的研究

目的研究转染neurturin基因(NTN)的骨髓基质细胞(BMSCs)移植治疗帕金森病模型大鼠,并探讨其治疗机制。方法将建模成功的帕金森病模型大鼠分为3组,将转染NTN基因的BMSCs(转基因组)、未转染NTN基因含空质粒的BMSCs(空质粒组)和生理盐水(生理盐水组)分别注入模型大鼠右侧的纹状体,在治疗后1-6个月分别观察大鼠阿朴吗啡诱导的旋转行为的变化。移植后第1个月分别进行大鼠脑冰冻切片荧光免疫组织化学鉴定[免疫荧光检测绿色荧光蛋白(GFP)分别与NTN(GFP／NTN)、胶质纤维酸性蛋白(GFAP)(GFP／GFAP)、神经元特异性烯醇化酶(NSE)(GFP／NSE)和酪氨酸羟化酶(TH)(GFP／TH)双标细胞]及检测1-6个月脑切片免疫组织化学TH阳性细胞并计数。原位杂交和蛋白印记法分别检测NTN在移植大鼠脑中mRNA和蛋白的表达。结果细胞移植后第1、2、3个月,转基因组大鼠的旋转次数[分别为(12．9±4．7)r／min、(9．4±3．3)r／min和(8．0±3．4)r／min]少于空质粒组[分别为(14．1±4．3)r／min、(12．5±4．8)r／min和(10．6±3．7)r／min],而这两组在1-6个月的旋转次数均少与生理盐水组[分别为(15．1±4．2)r／mn、(14．5±3．6)r／min、(13．8±3．7)r／min、(13．1±3．0)r／min、(12．9±2．8)r／min和(12．6±3．1)r／min](P<0．05),在移植后第1个月转基因组大鼠移植区可见GFP／NTN、GFP／GFAP、GFP／NSE双标的细胞,未发现GFP／TH双标的细胞。结论转基因组治疗帕金森病模型大鼠的总体疗效好于空质粒组和生理盐水组。     

宫内HBV感染小儿接种HB疫苗的细胞免疫功能研究

采用体外淋巴细胞培养方法对42例宫内HBV感染小儿接种HB疫苗，并进行非特异性及特异性淋巴细胞增殖试验的检测。结果发现在非特异性淋巴细胞增殖试验中，宫内HBV感染小儿接种HB疫苗无反应组的刺激指数(SI)值低于有反应组及正常免疫儿童(前者为63.35±13．81比73．77±12．76．P<0．05；后者为63．35±13．81比81．17±11．82，P<0．001);在特异性淋巴细胞增殖试验中，三者的SI值间也有显著差别(P<0．001)。同时应用间接免疫荧光技术对32例宫内HBV感染接种HB疫苗小儿进行外周血T淋巴细胞亚群的测定。发现CD3^ 细胞百分比三组间无明显差异(P>0．05)，而CD4^ ／CD8^ 比值在宫内HBV感染接种HB疫苗无反应组及有反应组均低于正常免疫儿童(前者为1．069=0．158比1．653±0．229，P<0。05；后者为1.316±0.120比1．653±0．229，P<0．05)。这些结果提示,宫内HBV感染小儿接种HB疫苗有无效果与其细胞免疫功能和免疫调控系统的作用是否正常有关。     

骨髓间质干细胞移植治疗原发性扩张型心肌病的疗效与安全性

目的研究自身骨髓间质干细胞经冠状动脉内移植治疗原发性扩张型心肌病的临床疗效及其安全性。方法入选24例原发性扩张型心肌病患者,随机分为对照组和细胞移植组各12例,两组均予常规抗心衰药物治疗。细胞移植组接受自身骨髓间质干细胞冠状动脉内移植,对照组冠状动脉内注射等量生理盐水。两组术前、术后48H、3个月和6个月分别检测血清白介素6(IL6)、肿瘤坏死因子Α(TNFΑ)和高敏C反应蛋白(HSCRP),术前、术后3个月和6个月分别行血浆脑钠肽(BNP)、超声心动图、动态心电检测和6MIN步行试验。结果细胞移植组术后上述三时间点的血清IL6、TNFΑ和HSCRP与对照组和自身术前比较均无统计学意义(P>0.05)。细胞移植组术后3个月和6个月BNP水平,较自身术前增高[(378.10±147.47),(420.40±148.50)比(292.40±148.54)NG/L,P<0.05],但较对照组降低,差异具统计学意义[3个月:(378.10±147.47)比(473.10±106.31)NG/L;6个月:(420.40±148.50)比(544.60±93.11)NG/L,P<0.05]。术后6个月,细胞移植组6MIN步行路程增加,与对照组和自身术前比较亦具统计学意义[(519.00±43.28)比(396.33±42.19),(464.00±76.5)M,P<0.05]。术后心超示两组间左室舒张末容积和左室射血分数无统计学意义(P>0.05)。围手术期及术后6个月随访中未见任何严重致心律失常等不良反应发生。随访期间两组患者生存率无统计学意义。结论自身骨髓间质干细胞经冠状动脉内移植治疗原发性扩张型心肌病,可降低血浆BNP水平,延长6MIN步行路程,在一定程度上增加运动耐量,无明显的致心律失常、栓塞和免疫炎症反应。     

The potential of brain natriuretic peptide as a biomarker for New York Heart Association class during the outpatient treatment of heart failure

BACKGROUND: Plasma C-terminal atrial natriuretic peptide (C-ANP), N-terminal ANP (N-ANP), and brain natriuretic peptide (BNP) have diagnostic utility in detecting left ventricular dysfunction. Their relative value in monitoring symptom status during the chronic treatment of congestive heart failure (CHF) remains undefined. METHODS AND RESULTS: Ninety-eight subjects with CHF were evaluated. Baseline natriuretic peptides were measured by radioimmunoassay, left ventricular ejection fraction (LVEF) was estimated with echocardiography, and New York Heart Association (NYHA) class was determined independently by attending heart failure specialists. Forty-one subjects were restudied during a 6- to 12-month follow-up period after optimizing therapy. At baseline, all natriuretic peptides and LVEF correlated positively with NYHA class (P <.005). Plasma BNP, however, correlated best with NYHA class. At follow-up, only changes of BNP correlated to changes of NYHA class (P =.04). BNP decreased (-45% +/- 12%, N = 14, P =.002) in subjects whose NYHA class improved whereas BNP remained unchanged (-1% +/- 10%, N = 25, P =.95) in those whose NYHA class was stable. CONCLUSIONS: This investigation demonstrates the superiority of plasma BNP as compared to ANP and LVEF in objectively assessing NYHA class during the chronic treatment of CHF. Given that clinical assessment of CHF is subjective, plasma BNP is a useful objective biomarker in monitoring human CHF in the outpatient setting.     

Neurohormonal determinants of peak oxygen uptake in patients with chronic heart failure

Chronic heart failure (CHF) is characterized by the activation of neurohormones and cytokines. This study determined whether peak oxygen uptake (VO2) can be predicted by the degree of neurohormonal and cytokine activations in CHF. Plasma norepinephrine. epinephrine, renin-angiotensin system activity, ANP, BNP, and serum interleukin-6 (IL-6) and tumor necrosis factor (TNF)-alpha were measured in 84 CHF patients (age, 59 +/- 1 years, LVEF, 36 +/- 1%) and 34 controls. Maximal cardiopulmonary exercise testing was performed. Peak VO2 (Controls vs CHF: 27.8 +/- 1.3 vs 18.2 +/- 0.5 mL/min/kg, P < 0.0001) was lower in CHF. Patients with CHF had increased plasma norepinephrine (211 +/- 11 vs 315 +/- 24 pg/mL), renin activity (1.2 +/- 0.2 vs 6.2 +/- 1.1 ng/mL/hr), ANP (22 +/- 3 vs 72 +/- 7 pg/mL), and BNP levels (18 +/- 3 vs 200 +/- 25 pg/mL) (all P < 0.01). Serum IL-6 (1.1 0.1 vs 2.4 +/- 0.3 pg/mL) and TNF-alpha (2.7 +/- 0.2 vs 4.0 +/- 0.3 pg/mL) levels were higher in CHF (both P < 0.001). Univariate analysis revealed that age (P < 0.001), cardiothoracic ratio (P < 0.001), norepinephrine (P < 0.0001), ANP (P < 0.001), BNP (P < 0.01), and log IL-6 (P < 0.05) were significantly related with peak VO2. Stepwise regression analysis indicated that plasma norepinephrine and ANP emerged as significant determinants of peak VO2, independent of patient age (overall R = 0.61, P < 0.0001). In summary, patients with CHF exhibited activation of neurohormones and proinflammatory cytokines. Among the elevated hormonal and cytokine markers, plasma norepinephrine and ANP levels were independent predictors of exercise capacity.     

双核素单光子断层显像评价骨髓单个核细胞移植后急性心肌梗死患者存活心肌变化

目的 利用双核素[^201 铊（Tl）及^18 F-脱氧葡萄糖（FDG）]单光子断层显像（SPECT）方法评价经冠状动脉自体骨髓单个核细胞（BM-MNC）移植对急性心肌梗死患者心功能和存活心肌的影响。方法 40例首次ST段抬高急性心肌梗死患者,成功完成PCI术后,随机分为细胞移植组（n=20）和对照组（n=20）,急诊冠状动脉造影术同时,经微导管于梗死相关动脉内支架远端注入自体BM-MNC悬液或等量的肝素生理盐水。研究终点为PCI术后6个月时双核素（^201 Tl及^18F-FDG）SPECT测定存活心肌的变化。结果 随访6个月时,两组患者左心室射血分数均有显著提高,但移植组患者左室射血分数改善幅度更显著[（7．6±2．8）％比（3．0±2．8）％,P〈0．001]。^201 Tl-SPECT显示移植组患者左心室心肌灌注明显改善,心肌灌注缺损面积减少（6．7±3．0）％,同时^18 F—FDG-SPECT结果显示梗死边缘区心肌灌注-代谢不匹配面积明显增加,提示存活心肌明显增加。结论 自体BM-MNC可以改善急性心肌梗死后梗死边缘区心肌灌注,增加局部存活心肌,提高左心室功能。     

骨髓单个核细胞移植对缺血性心肌病患者血浆利钠肽水平的影响

目的:观察骨髓单个核细胞(mononuclear bone marrow cell,MBMC)移植对缺血性心肌病患者左心功能及血浆利钠肽的影响。方法:36例缺血性心肌病患者分为细胞移植组24例和常规治疗组12例。结果:治疗3d后移植组及对照组心房利钠肽(atrial natriuretic peptide,ANP)、脑利钠肽(brain natriuretic peptide,BNP)均无明显变化,治疗7d后,移植组BNP下降了67.76%,对照组下降了24.1%;移植组ANP上升36.65%,而对照组下降14%,超声心动图结果显示:移植组左心室射血分数(LVEF)由(34.8±1.27)%升至(44.45±2.08)%(P<0.001),对照组LVEF由(36.20±3.80)%升至(38.97±2.76)%(P<0.05)。结论:MBMC经冠状动脉移植后早期(1周内)可明显改善心力衰竭患者的心功能,其机制之一可能为外源ANP生成而发挥的利钠、利尿、扩血管作用。     

Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study

BACKGROUND: Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF. METHODS AND RESULTS: We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01). CONCLUSIONS: Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.     

Possible vascular role of increased plasma arginine vasopressin in congestive heart failure

BACKGROUND: The present study was undertaken to determine the relation of cardiac dysfunction with hormonal release in patients with congestive heart failure. METHODS: Seventy-two patients with congestive heart failure were examined, who were divided into four subgroups classified by the criteria of the New York Heart Association (NYHA). Also, 10 age-matched subjects were served as a control. Plasma arginine vasopressin (AVP), norepinephrine, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were determined. Cardiac index and pulmonary capillary wedge pressure (PCWP) were measured in 51 of 72 patients. RESULTS: Plasma AVP levels were significantly increased according to the severity of NYHA classes; control: 1.7 +/- 0.2; NYHA I: 4.9 +/- 0.8, NYHA II: 5.5 +/- 0.9, NYHA III: 13.4 +/- 2.6 (p < 0.05), NYHA IV: 26.9 +/- 5.6 pmol/l (p < 0.001). Similar results were obtained with plasma norepinephrine, ANP and BNP. Plasma AVP levels had negative correlation with cardiac index (r = -0.36, p < 0.01), but did not with PCWP and plasma osmolality. Plasma BNP levels positively correlated with PCWP (r = 0.44, p < 0.001), but did not with cardiac index. There was no correlation between plasma AVP and BNP. Intensive therapy profoundly reduced all the hormones according to the improvement of cardiac index in the patients with NYHA class III and IV. The percent decrease in plasma AVP was 60.0%, a value greater than that in plasma BNP. CONCLUSION: The present study indicates that increased AVP may deteriorate cardiac function through V(1a) as well as V(2) action, and that plasma AVP level is also a proper marker for the presence and severity of congestive heart failure.     

Cardiac toxicity of high-dose cyclophosphamide and melphalan in patients with multiple myeloma treated with tandem autologous hematopoietic stem cell transplantation

Tandem autologous hematopoetic stem cell transplantation (HSCT) is an effective treatment in patients with multiple myeloma (MM). Patients receive high-dose cyclophosphamide (CY) followed by two myeloablative dosages of melphalan (MEL). Cardiotoxicity treatment related data are scanty. In 30 patients with MM chemotherapy was followed by high-dose CY (cycle CY), and two autologous tandem HSCT treatments with MEL (cycles MEL I and MEL II). During each 15-day treatment troponin I (TnI), brain natriuretic peptide (BNP) and endothelin-1 (ET-1) were controlled at six time points. All patients underwent conventional and tissue Doppler echocardiography prior to CY therapy (Eho 0), before cycle MEL I (Eho 1), before cycle MEL II (Eho 2), and 3 months after the completion of therapy (Eho 3). None of the patients developed clinical signs of heart failure. The peak TnI concentrations were noted at days 8, 11, and 15 during all three chemotherapy cycles. During all three cycles there was a significant increase in baseline BNP concentrations and BNP levels measured at day 1 after treatment with CY and MEL (CY: P = 0.0001, MEL I: P = 0.001, MEL II: P = 0.001). The highest BNP concentration occurred during CY treatment (0.517 +/- 0.391 mug/L). During cycles MEL I and MEL II we noted the peak BNP concentrations at day 4 following chemotherapy (MEL I 0.376 +/- 0.418 mug/L; MEL II 0.363 +/- 0.379 mug/L). During all three cycles the highest ET-1 levels occurred at day 1 after chemotherapy (CY 1.146 +/- 1.313 ng/L; MEL I 1.054 +/- 2.242 ng/L; MEL II 0.618 +/- 0.539 ng/L). A significant increase in ET-1 concentrations relative to the basal values occurred only in cycle MEL II (P = 0.003). The duration of wave a in the Doppler pulmonary vein flow increased significantly (Eho 0/Eho 1: P = 0.008, Eho 0/Eho 3: P = 0.026). There was a significant decrease in the A/a ratio in flow velocities during chemotherapy (Eho 0/Eho 1: P = 0.002, Eho 0/Eho 3: P < 0.0001). Early diastolic tissue Doppler velocities (E (m)) decreased significantly during individual cycles of chemotherapy (P = 0.006). A significant post-treatment increase in the incidence of mitral regurgitation was observed (Eho 0/Eho 3: P = 0.003). Treatment of MM patients with tandem autologous HSCT is cardiotoxic. Our patients did not develop clinically overt heart failure or myocardial necrosis. Increased plasma levels of BNP and ET-1 were compatible with transient neurohormonal activation of heart failure. Doppler echocardiography studies revealed worsening of left ventricular diastolic function and occurrence of functional mitral regurgitation.     

Direct comparison between endothelin-1, N-terminal proatrial natriuretic factor, and brain natriuretic peptide as prognostic markers of survival in congestive heart failure

BACKGROUND: Endothelin-1 (ET-1) and cardiac natriuretic peptide plasma concentrations have prognostic significance in congestive heart failure (CHF). However, their respective prognostic values in this setting have never been directly compared. METHODS AND RESULTS: We studied the prognostic performances of ET-1, N-terminal proatrial natriuretic factor (N-proANF), and brain natriuretic peptide (BNP) to predict the long-term cardiac mortality in fully treated patients with CHF. Peripheral plasma concentrations of the 3 peptides were measured in 109 patients (left ventricular ejection fraction [LVEF] < 35%) in New York Heart Association (NYHA) functional classes II (n = 65) or III to IV (n = 44). The outcome of the patients was evaluated 3 years after the beginning of the study, and a Cox regression model was used to identify predictors of death. Plasma concentrations of the 3 peptides increased with the severity of heart failure. By univariate analysis, 6 parameters were significantly associated with death during follow-up: ET-1 level, NYHA classes III to IV, N-proANF level, BNP level, LVEF, and age (all P < .01). By multivariate analysis, only ET-1 level and, to a lesser extent, N-proANF level contributed significantly and independently to risk stratification (chi2 = 53.4 and 12.8; P < .0001 and P < .001, respectively). CONCLUSION: In a group of patients in whom the vast majority were administered angiotensin-converting enzyme inhibitor therapy, plasma ET-1 and N-proANF concentrations identify better than several clinical markers a very high-risk group, fairly amenable to heart transplantation or new therapies.