Efficacy and Safety of 1-Hour Infusion of Recombinant Human Atrial Natriuretic Peptide in Patients With Acute Decompensated Heart Failure: A Phase III, Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial.

The aim of the study was to evaluate the efficacy and safety of 1-h infusion of recombinant human atrial natriuretic peptide (rhANP) in combination with standard therapy in patients with acute decompensated heart failure (ADHF). This was a phase III, randomized, double-blind, placebo-controlled, multicenter trial. Eligible patients with ADHF were randomized to receive a 1-h infusion of either rhANP or placebo at a ratio of 3:1 in combination with standard therapy. The primary endpoint was dyspnea improvement (a decrease of at least 2 grades of dyspnea severity at 12 h from baseline). Reduction in pulmonary capillary wedge pressure (PCWP) 1 h after infusion was the co-primary endpoint for catheterized patients. Overall, 477 patients were randomized: 358 (93 catheterized) patients received rhANP and 118 (28 catheterized) received placebo. The percentage of patients with dyspnea improvement at 12 h was higher, although not statistically significant, in the rhANP group than in the placebo group (32.0% vs 25.4%, odds ratio=1.382, 95% confidence interval [CI]: 0.863-2.212, P = 0.17). Reduction in PCWP at 1 h was significantly greater in patients treated with rhANP than in patients treated with placebo (-7.74 ±â€Š5.95 vs -1.82 ±â€Š4.47 mm Hg, P < 0.001). The frequencies of adverse events and renal impairment within 3 days of treatment were similar between the 2 groups. Mortality at 1 month was 3.1% in the rhANP group vs 2.5% in the placebo group (hazard ratio = 1.21, 95% CI: 0.34-4.26; P > 0.99). 1-h rhANP infusion appears to result in prompt, transient hemodynamic improvement with a small, nonsignificant, effect on dyspnea in ADHF patients receiving standard therapy. The safety of 1-h infusion of rhANP seems to be acceptable. (WHO International Clinical Trials Registry Platform [ICTRP] number, ChiCTR-IPR-14005719.).

Simultaneous quantitative analysis of fasudil and its active metabolite in human plasma by liquid chromatography electro-spray tandem mass spectrometry.

A fast and sensitive method to quantify fasudil hydrochloride (FH) and its active metabolite hydroxyfasudil (M3) in human plasma using HPLC-MS/MS has been developed and validated in present study. The method involved simple sample preparation with methanol as protein precipitation (3:1, v/v) and ranitidine as an internal standard (IS). The analytes and IS were separated using a gradient elution procedure on the analytical column ZORBAX StableBond-C18 (5 microm, 150 mm x 4.6mm). Detection was performed by an AB 3200 QTRAP tandem mass spectrometer equipped with a Turbo IonSpray ionization source set in positive ion mode. Multiple reaction monitoring (MRM) using the precursor to product ion was m/z 292.2/99.2 for fasudil, m/z 308.2/99.2 for M3 and m/z for 315.3/176.2 for IS. The linear range of the method was from 0.4 to 250 ng/mL for both fasudil and M3. The lower limit of quantification was 0.4 ng/mL for both fasudil and M3. The intra- and inter-day relative standard deviation over the entire concentration range was less than 7.11% for fasudil and 10.6% for M3, respectively. The validated method was successfully applied for the evaluation of pharmacokinetic of fasudil hydrochloride after administration of 30 mg fasudil hydrochloride by continuous intravenous infusion over 30 min in 12 healthy Chinese volunteers.

[Clinical characteristics of and related treatments on 1004 patients with acute myocardial infarction from March 2004 to March 2007].

OBJECTIVE: To study the change of baseline clinical characteristics including prehospital delayed time (PDT), modes of transportation and treatment for patients with acute myocardial infarction (AMI) in the past 3 years. METHODS: We used the same questionnaire to accurately collect and retrospectively analyze the data regarding clinical characteristics of all 1004 patients with AMI, who consecutively presented to the Emergency Unit and Emergency Intensive Care Unit (EICU) of Beijing Anzhen Hospital from March 12th 2004 to March 11th 2007. According to the time of onset of the disease, all patients were divided into 3 groups: group A (from Mar. 12th 2004 to Mar. 11th 2005), group B (Mar. 12th 2005 to Mar 11th 2006) and group C (Mar. 12th 2006 to Mar. 11th 2007). Clinical characteristics and treatment were compared. RESULTS: There were significant differences in the number of patients with histories of stroke, coronary artery disease or smoking among the three groups (P < 0.05). No obvious differences in the median of PDT were found among the three groups (P > 0.05). More patients accepted reperfusive therapy in group C compared to group A (P < 0.05), although the mortality rates of AMI among these 3 years were similar. CONCLUSION: Though more people started to have accepted reperfusion therapy, mortality failed to show an obvious decrease. Subject as how to shorten the PDT called for further study.

[Clinical implications of relationship between myeloperoxidase and acute coronary syndromes].

OBJECTIVE: To investigate the clinical implications of relationship between myeloperoxidase and acute coronary syndromes (ACS). METHODS: 176 consecutive patients who underwent coronary angiography for coronary atherosclerosis were divided into four groups according to the quartile of MPO Level. The characters and the relationship between MPO and the elements were studied in every group. RESULTS: (1) ACS rate (36.2%) in the fourth quartile group of MPO level was 6 times higher than that (5.2%) in the first quartile group of MPO level, P < 0.01. (2) Gensini score (65.6 +/- 30.3) in the fourth quartile group of MPO level was significantly higher than that (17.3 +/- 10.2) in the first quartile group (P < 0.01). WBC [(7.7 +/- 1.6) x 10(9)/L] in the fourth quartile group was also significantly higher than that [(6.6 +/- 1.8) x 10(9)/L] in the first quartile group, P < 0.05. (3) When TnI < or = 0.05 ng/ml, MPO level had a positive correlation with Gensini score (r = 0.321, P = 0.002) and WBC (r = 0.230, P = 0.025). (4) Kaplan-meier event rate curve showed that there was a significant difference of the terminus incident (death, no causing death AMI, vessel reestablish and incidence rate of CABG add up) between the groups > or = 62.9 AUU/L and < 62.9 AUU/L of MPO serum level at 6-month follow-up visit (chi(2) = 13.5, P = 0.01). CONCLUSION: Activity level of MPO in human serum seems a good biomarker for diagnosing and predicting ACS, which may be especially helpful in predicting the risk of myocardial infarction in patients with acute chest pain during 6-month follow up.

Trans-coronary transplantation may be an optimal route in cellular cardiomyoplasty with stem cells.

Myocardial infarction is the leading cause of congestive heart failure and death in the industrialized world. However, the intrinsic repair mechanism of the injured heart and current therapeutic means are inadequate to regenerate lost myocardium. Recent interests focused on cellular cardiomyoplasty which is an outside intervention to support the reparative process in the heart through transplantation of stem/progenitor cells. Cellular myocardioplasty with stem cells is a possible option to reverse the adverse hemodynamic and neurohormonal imbalance after myocardial infarction. Experimental studies and clinical trials suggest that cellular cardiomyoplasty with stem/progenitor cells may improve cardiac function and prevent ventricular remodeling of the injured heart. Although the mechanisms are still in intensive debate, cellular cardiomyoplasty with stem cells has already been introduced into the clinical settings. However, it is an important challenge how donor cells are delivered to the targeted area. In early studies in animals, intramyocardial injection of stem cells after thoracotomy is the main transplantation route which is not suitable to most patients in clinical settings. Then the catheter-based infusion of stem cells is clinically introduced and rapidly developed because of its safety, convenience and micro-invasion. We hypothesize that catheter-based transplantation with stem cells may be a promising means to treat ischemic heart diseases in the future in clinical settings.

[Upregulation of adrenomedullin system in left ventricular hypertrophy of severe hypertension rats].

OBJECTIVE: To investigate the pathophysiological role of the cardiac adrenomedullin (AM) system, including the ligand and amidating activity in the hypertrophied heart in severe hypertension. METHODS: The following four groups were studied: control Wistar Kyoto rats (WKY), spontaneously hypertensive stroke-prone rats (SHR-SP), 8 weeks captopril-treated SHR-SP, and 8 weeks trichlormethiazide-treated SHR-SP. AM precursor was converted to inactive glycine-extended AM (AM-Gly) and subsequently AM-Gly was converted to active mature AM (AM-m) by enzymatic amidation. AM-m, AM-total (AM-T; AM-T = AM-m + AM-Gly), atrial natriuretic peptide (ANP) in the plasma and left ventricle (LV) by immunoradiometric assay, and gene expression of AM and ANP were measured. RESULTS: SHR-SP had increased blood pressure, LV weight, plasma and LV ANP levels and mRNA levels of ANP compared with WKY. AM-m and AM-T levels in the plasma (AM-m: +31%; AM-T: +56%) and in the LV (AM-m: +84%; AM-T: +31%) were significantly higher in SHR-SP than those in WKY. The LV tissue AM-m/AM-T ratio was significantly higher in SHR-SP (93.2%) than that in WKY. The mRNA levels of AM in the LV were significantly higher in SHR-SP than those in WKY. Captopril and trichlormethiazide similarly decreased blood pressure and LV hypertrophy with the reduction of the LV AM-m and AM-T levels and mRNA abundance of AM. CONCLUSIONS: These results suggested that cardiac AM system was upregulated in the hypertrophied heart in this hypertension model. Considering that AM being as an antiremodeling autocrine and(or) paracrine factor, upregulation of the AM system may modulate the pathophysiological course in LV hypertrophy.