Circulating interleukin-6 significantly correlates to thyroid hormone in acute myocardial infarction but not in chronic heart failure

To investigate relationships between thyroid states and the cardiac endocrine system, we analyzed thyrotropin (TSH), thyroid hormone, plasma levels of interleukin-6 (IL-6) and brain natriuretic peptide (BNP) in 50 patients with chronic heart failure (CHF), in 30 patients with heart failure from acute myocardial infarction (AMI), and in 15 controls. Plasma levels of IL-6 and BNP in both CHF and AMI were significantly elevated, while free triiodothyronine (FT3) was significantly decreased compared to controls. FT3/free thyroxine (FT4) ratio was significantly decreased in CHF but not in AMI compared to controls. In CHF, diuretic treatment diminished circulating BNP but not IL-6, while diuretic treatment increased FT3/FT4 ratio. In AMI, FT3/FT4 ratio was significantly decreased 72 h compared to 12 h after the onset of AMI, while BNP and IL-6 were significantly increased 72 h compared to 12 h after the onset of AMI. In both CHF and AMI, BNP significantly correlated with FT4. On the other hand, significant correlations between IL-6 and FT3, and between IL-6 and FT3/FT4 ratio were detected in AMI but not in CHF. This preliminary study suggests that IL-6, BNP and thyroid hormone reflect ventricular dysfunction in both acute and chronic heart failure, and that IL-6 significantly relates to circulating thyroid hormone in AMI but not in CHF.     

急性心肌梗死KillipⅡ级患者经皮冠状动脉介入治疗后血浆脑钠素、心钠素水平的变化

目的研究急性心肌梗死(acutemyocardialinfarction,AMI)伴左心力衰竭患者经皮冠状动脉介入治疗(PCI)后心钠素(atrialnatriureticpeptide,ANP)和脑钠素(brainnatriureticpeptide,BNP)二种因子的变化及其临床意义。方法入选AMIKillipⅡ级患者40例作为试验组,在AMI1周内行PCI治疗,另入选AMIKillipⅡ级未行PCI治疗患者40例作为对照组。试验组患者于AMI48h内,PCI术后24h,术后1个月时,对照组患者在相对应的时间,采集肘静脉血,采用酶联免疫吸附法分析,测血浆ANP及BNP水平。结果两组间ANP、BNP水平比较,试验组患者AMI48h内,血浆ANP、BNP水平均与对照组相似,两者间无显著性差异(P>0.05)。PCI术后24h,术后1个月ANP、BNP水平均较对照组明显降低,两组间有显著性差异(P<0.05);组内比较,试验组患者PCI术后24hANP、BNP水平较AMI48h内减低,但两者间无显著性差异(P>0.05);PCI术后1月ANP、BNP水平较术前明显回落,两者有显著性差异(P<0.05)。对照组患者在相对应的PCI术后24h,术后1个月这一时限ANP、BNP水平较AMI48h内无明显变化(P>0.05)。结论本研究发现AMIKillipⅡ级患者经PCI治疗可使血浆ANP、BNP水平降低。     

Angiotensin II type 1 receptor antagonist decreases plasma levels of tumor necrosis factor alpha, interleukin-6 and soluble adhesion molecules in patients with chronic heart failure

OBJECTIVES: To evaluate the effects of an angiotensin (Ang II) type 1 receptor antagonist on immune markers in patients with congestive heart failure (CHF). BACKGROUND: Ang II stimulates production of immune factors via the Ang II type 1 receptor in vitro, and the long-term effects of Ang II type 1 receptor antagonists on plasma markers of immune activation are unknown in patients with CHF. METHODS: Twenty-three patients with mild to moderate CHF with left ventricular dysfunction were randomly divided into two groups: treatment with Ang II type 1 receptor (candesartan cilexetil) (n = 14) or placebo (n = 9). We measured plasma levels of immune factors such as tumor necrosis factor alpha (TNFalpha), interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1). We also measured plasma levels of the neurohumoral factors such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and cyclic guanosine monophosphate (cGMP), a biological marker of ANP and BNP. RESULTS: Plasma levels of TNFalpha, IL-6, sICAM-1 and sVCAM-1 were increased in the 23 CHF patients compared with normal subjects and significantly decreased after 14 weeks of candesartan cilexetil treatment, but did not change in the placebo group. Plasma levels of BNP, which is a marker of ventricular injury, significantly decreased, and the molar ratio of plasma cGMP to cardiac natriuretic peptides (ANP + BNP) was significantly increased after candesartan cilexetil treatment, but did not change in the placebo group. CONCLUSIONS: These findings suggest that 14 weeks of treatment with an Ang II type 1 receptor antagonist (candesartan cilexetil) decreased plasma levels of the immune markers such as TNFalpha, IL-6, sICAM-1 and sVCAM-1 and that it improved the biological compensatory action of endogenous cardiac natriuretic peptides in patients with mild to moderate CHF.     

Effects of enhanced external counterpulsation on hemodynamics and its mechanism.

BACKGROUND: The hemodynamic effects of enhanced external counterpulsation (EECP) and its mechanism(s) were investigated in relation to neurohumoral factors in patients with acute myocardial infarction (AMI). METHODS AND RESULTS: Twenty-four patients with AMI were studied before, during and after EECP treatment for 60 min. Heart rate (HR), right atrial pressure (RAP), pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were determined. In addition, circulating concentrations of neurohumoral factors were determined at each time point. HR did not change following EECP treatment. However, RAP and PCWP increased significantly and CI was significantly elevated during EECP and thereafter. Blood atrial natriuretic peptide (ANP) concentration was significantly increased 15 and 60 min after the start of EECP treatment, but brain natriuretic peptide (BNP) did not change. Renin, aldosterone and catecholamine concentrations also did not change. CONCLUSION: Treatment with EECP resulted in an increased preload because of increased venous return, and CI was increased thereafter. In patients with AMI, EECP increased blood ANP concentration, but not BNP, which suggests that an increase in ANP without an increase in BNP is an important mechanism for the effects of EECP treatment.     

Effect of interleukin-1 beta on cardiac hypertrophy and production of natriuretic peptides in rat cardiocyte culture

This study was designed to examine the effects of interleukin-1 beta (IL-1 beta) on myocyte (MC) hypertrophy and the production of A-type natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in rat ventricular cardiocyte culture, and to investigate the role of nonmyocyte (NMC) in this process. We examined the effects of IL-1 beta on the production of ANP and BNP in comparison with the effects of endothelin-1 (ET-1) by using two types of neonatal rat cardiocyte culture; MC-enriched culture and MC-NMC coculture. In the MC-enriched culture, the increase in secretion of ANP and BNP was small in treatment with IL-1 beta (1000 pg/ml), while ET-1 (10 nM) markedly augmented the secretion of ANP and BNP. In the MC-NMC coculture, IL-1 beta and ET-1 each significantly augmented the secretion of ANP and BNP. The degree of the increase of ANP and BNP was equivalent between IL-1 beta and ET-1. As for the morphological changes of MCs, IL-1 beta induced the star-shaped MC hypertrophy characterized by elongation and pointed edges only in the MC-NMC coculture, while ET-1 induced the MC hypertrophy characterized by shapes of squares, triangles or circles in both cultures. This study shows that IL-1 beta induces unique cardiac hypertrophy and the marked secretion of ANP and BNP, and that NMC is indispensable when treated with IL-1 beta.     

Neurohormones and cytokines in heart failure. Correlation with coronary flow reserve

INTRODUCTION AND OBJECTIVES: In heart failure, the coronary flow reserve (CFR) measured by positron-emission tomography (PET) is reduced. As neurohormone and cytokine levels are also altered in patients with the condition, our aim was to determine whether there is a correlation between CFR and neurohormone and cytokine levels. PATIENTS AND METHOD: The study included 40 patients with heart failure but without ischemic heart disease. Myocardial blood flow was measured by PET using nitrogen-13 ammonia at baseline and during ATP infusion. The CFR was calculated for each patient. In addition, levels of the following were determined: norepinephrine, endothelin-1, angiotensin-II, atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), tumor necrosis factor-alpha, interleukin (IL)-1beta, soluble IL-2 receptor, and IL-6. RESULTS: All neurohormone levels were elevated above reference values. The levels of all cytokines, except IL-1beta, were also elevated. There was a significant negative correlation between CFR and the levels of several neurohormones: ANP (r=-0.476), BNP (r=-0.442), and IL-6 (r=-0.509). CONCLUSIONS: In heart failure, the decrease in CFR is correlated with increases in the levels of certain neurohormones (i.e., ANP and BNP) and cytokines (i.e., IL-6), with vasodilatory effect. These increases are probably are related to compensatory mechanisms that are unable to correct for the endothelial dysfunction present in these patients.     

Effects of human atrial natriuretic peptide on cardiac function and hemodynamics in patients with high plasma BNP levels

Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) bind preferentially to the natriuretic peptide A receptor. Therefore, we hypothesized that the positive inotropic and lusitropic effects of ANP might be blunted in patients with moderate congestive heart failure and high BNP levels. Micromanometers and conductance catheters were used to obtain relatively load-insensitive left ventricular pressure-volume analysis in order to compare the myocardial and load-altering actions of ANP in 20 patients with low and high plasma BNP levels. In the low-BNP group (plasma BNP levels <230 pg/ml), ANP infusion significantly decreased end-systolic pressure and end-diastolic pressure and volume, increased end-systolic elastance, and shortened left ventricular relaxation. By contrast, in the high-BNP group (plasma BNP levels >230 pg/ml), the effect of ANP infusion on LV contractility was blunted but its beneficial effects on LV diastolic function and LV-arterial coupling remained. Thus, ANP infusion may improve LV diastolic function even in patients with moderate heart failure and high plasma BNP levels.     

Anemia is an independent predictor for elevated plasma levels of natriuretic peptides in patients undergoing cardiac catheterization for coronary artery disease.

BACKGROUND: It is unknown whether the association of anemia with elevated plasma levels of B-type and atrial natriuretic peptides (BNP and ANP) is mediated by the hemodynamic effects of anemia. METHODS AND RESULTS: The study group comprised 237 consecutive patients (BNP, median [interquartile range], 28.3 [9.5-77.1] pg/ml; ANP, 17.8 [8.5-39.0] pg/ml) undergoing determination of hemoglobin (Hb) and natriuretic peptide levels and cardiac catheterization for evaluation of coronary artery disease (CAD). Hb correlated with BNP (r=-0.36, p<0.001) and ANP (r=-0.35, p<0.001). Patients with anemia (Hb <12 g/dl for females; <13 g/dl for males, n=63) were more likely to be older with reduced body mass index and renal function, greater severity of CAD and to have higher heart rate, mean pulmonary capillary wedge pressure, and cardiac output. Anemia was a significant predictor for elevated (>third quartile value) natriuretic peptide levels and the predictive value remained significant after adjustment for other predictors, including increased left ventricular end-diastolic pressure and differences in clinical and hemodynamic variables between patients with and without anemia (adjusted odds ratio [95% confidence interval] for elevated BNP and ANP levels, 7.39 [2.76-19.8] and 2.56 [1.08-6.07], respectively). CONCLUSION: Anemia is an independent predictor for elevated natriuretic peptide levels in patients with known or suspected CAD.     

利钠肽的心脏保护作用

心钠肽和脑钠肽作为心源性循环激素在调节血容量和血管张力方面具有重要作用,近年研究显示他们不仅作为循环激素而且作为局部自分泌和/或旁分泌因子发挥心脏保护作用,如抗心肌肥厚和抗纤维化作用。另外,利钠肽/cGMP系统在心力衰竭、心肌梗死及心肌缺血/再灌注损伤的病理生理中具有重要作用。最近,人类重组心钠肽和脑钠肽用于临床心力衰竭治疗已取得一定进展。现就以上做一综述。     

Brain natriuretic peptide increases acutely and much more prominently than atrial natriuretic peptide during coronary angioplasty

BACKGROUND: Increased levels of plasma brain natriuretic peptide (BNP) are observed in patients with congestive heart failure, hypertension, left ventricular hypertrophy, and acute myocardial infarction. However, there are no data on serial changes in plasma levels of BNP in patients undergoing coronary angioplasty. HYPOTHESIS: The study was undertaken to examine plasma concentrations of BNP together with those of atrial natriuretic peptide (ANP) in patients undergoing percutaneous transluminal coronary angioplasty (PTCA). METHODS: Plasma concentrations of BNP and ANP were examined in 13 patients with stable angina pectoris and good left ventricular function undergoing PTCA. Blood samples were taken from the femoral vein at baseline, after the first balloon inflation, after the end of the procedure, and 4 h thereafter. RESULTS: Plasma BNP levels were 14 +/- 4 at baseline, 22 +/- 10 after the first balloon inflation, 28 +/- 12 at the end of the procedure, and 15 +/- 4 pgr/ml 4 h thereafter (F = 13.05, p < 0.00001). Plasma ANP levels were 80 +/- 15, 86 +/- 14, 90 +/- 24, and 75 +/- 6 fmol/l (F = 5.95, p = 0.002), respectively. The increase of BNP at the end of the procedure was related to the increase of ANP (r = 0.78, p = 0.002). CONCLUSION: Plasma BNP levels increase acutely and much more prominently than those of plasma ANP during coronary angioplasty; however, plasma BNP levels return to baseline values shortly after the end of the procedure.