赖诺普利对高血压患者心钠素及左室肥厚的影响

目的：探讨高血压（EH）患者心钠素（ANP））、空腹血清胰岛素（FINS）与左室肥厚（LVH）的关系以及赖诺普利对其的影响。方法：入选病例为符合2005年《中国高血压防治指南》标准的1级、2级EH伴LVH的患者60例,随机分为赖诺普利组30例,卡托普利组30例。检测口服赖诺普利或卡托普利前后ANP、FINS的含量;采用彩色多普勒超声检测LVH。样本数据分析采用t检验或多元线性回归。结果：赖诺普利较卡托普利降低ANP、FINS及改善LVH效果更显著（P〈0.05）;ANP、FINS与LVH无相关性。结论：赖诺普利可降低ANP、FINS。     

Effects of nocturnal noninvasive mechanical ventilation on heart rate variability of patients with advanced COPD

BACKGROUND: Cardiovascular comorbidities have a negative impact on the health status and prognosis of patients with COPD. We determined whether nocturnal noninvasive (positive) mechanical ventilation (NIMV) can improve heart rate variability (HRV), decrease circulating natriuretic peptide levels, and improve functional performance of patients with very advanced COPD. METHODS: A randomized, double-blind, parallel controlled trial was conducted in 23 participants with stable but advanced COPD. Participants received standard medical therapy plus nocturnal NIMV or standard medical therapy plus sham NIMV for 3 months. RESULTS: After 3 months of NIMV therapy, the 24-h triangular interpolation of N-N intervals increased from 322 to 473 ms (p = 0.034), the 24-h HRV index (HRVI) increased from 21.8 to 29.9 ms (p = 0.035), nocturnal HRVI increased from 6.1 to 8.0 ms (p = 0.026), and the SD of the average N-N interval increased from 37 to 41 ms (p = 0.020). None of these indexes changed significantly in the control group. Additionally, compared with the control group, the pro-atrial natriuretic peptide levels declined significantly in the NIMV group (p = 0.013). CONCLUSIONS: NIMV applied nocturnally over 3 months may improve HRV, reduce circulating natriuretic peptide levels, and enhance the functional performance of patients with advanced but stable COPD. While not definitive due to small sample size, these data suggest that nocturnal NIMV may reduce the impact of cardiac comorbidities in COPD patients.     

Natriuretic peptides

Natriuretic peptides (NPs) are released from the heart in response to pressure and volume overload. B-type natriuretic peptide (BNP) and N-terminal-proBNP have become important diagnostic tools for assessing patients who present acutely with dyspnea. The NP level reflects a compilation of systolic and diastolic function as well as right ventricular and valvular function. Studies suggest that using NPs in the emergency department can reduce the consumption of hospital resources and can lower costs by either eliminating the need for other, more expensive tests or by establishing an alternative diagnosis that does not require hospital stay. Caveats such as body mass index and renal function must be taken into account when analyzing NP levels. Natriuretic peptide levels have important prognostic value in multiple clinical settings, including in patients with stable coronary artery disease and with acute coronary syndromes. In patients with decompensated heart failure due to volume overload, a treatment-induced drop in wedge pressure is often accompanied by a rapid drop in NP levels. Knowing a patient's NP levels might thus assist with hemodynamic assessment and subsequent treatment titration. Monitoring NP levels in the outpatient setting might also improve patient care and outcomes.     

Augmented potassium current is a shared phenotype for two genetic defects associated with familial atrial fibrillation

Mutations in multiple genes have been implicated in familial atrial fibrillation (AF), but the underlying mechanisms, and thus implications for therapy, remain ill-defined. Among 231 participants in the Vanderbilt AF Registry, we found a mutation in KCNQ1 (encoding the α-subunit of slow delayed rectifier potassium current [I_Ks]) and separately a mutation in natriuretic peptide precursor A (NPPA) gene (encoding atrial natriuretic peptide, ANP), both segregating with early onset lone AF in different kindreds. The functional effects of these mutations yielded strikingly similar I_Ks “gain-of-function.” In Chinese Hamster Ovary (CHO) cells, coexpression of mutant KCNQ1 with its ancillary subunit KCNE1 generated ∼ 3-fold larger currents that activated much faster than wild-type (WT)-I_Ks. Application of the WT NPPA peptide fragment produced similar changes in WT-I_Ks, and these were exaggerated with the mutant NPPA S64R peptide fragment. Anantin, a competitive ANP receptor antagonist, completely inhibited the changes in I_Ks gating observed with NPPA S64R. Computational simulations identified accelerated transitions into open states as the mechanism for variant I_Ks gating. Incorporating these I_Ks changes into computed human atrial action potentials (AP) resulted in 37% shortening (120 vs. 192 ms at 300 ms cycle length), reflecting loss of the phase II dome which is dependent on L-type calcium channel current. We found striking functional similarities due to mutations in KCNQ1 and NPPA genes which led to I_Ks “gain-of-function”, atrial AP shortening, and consequently altered calcium current as a common mechanism between diverse familial AF syndromes.     

The biochemical pharmacology of renin inhibitors: Implications for translational medicine in hypertension, diabetic nephropathy and heart failure: Expectations and reality

The renin-angiotensin-aldosterone system (RAAS) plays a dominant role in the pathophysiology of hypertension, Diabetes mellitus (DM), chronic kidney disease (CKD) and chronic heart failure (CHF). Therefore, drugs that block key components of the RAAS such as ACE inhibitors (ACEi) and angiotensin receptor blockers (ARBs) have gained wide clinical use for these indications. Despite progress, the morbidity and mortality of patients treated with ACEi or ARBs remain high. Small molecules that directly inhibit renin (DRI) and are orally active have also been developed and one such drug, aliskiren, was introduced into clinical use for treatment of hypertension in 2007. Further clinical trials aimed to expand the therapeutic use of aliskiren are in progress for CKD-DM and CHF. In this review we analyze and review the translational medicine prospects of aliskiren in respect to the biochemical pharmacology of the RAAS, the marketed RAAS modulators and the new emerging science regarding the role of prorenin, renin and renin receptors in cardiovascular biology and disease. The information already gained with aliskiren, raises questions regarding the advantages of DRIs as monotherapy compared to marketed ACEis and ARBs, their potential added value in combination with other RAAS modulators and other unproven benefits in relation to prorenin and renin receptor biology. This review will also indicate basic and clinical research needs that are critical to determine whether DRIs can provide meaningful added medical benefits over contemporary medicines that regulate the RAAS, and the need to identify patients that are more likely to benefit from DRIs and any possible long term adverse effects.     

Biochemical and pharmacological characterization of P-site inhibitors on homodimeric guanylyl cyclase domain from natriuretic peptide receptor-A

Guanylyl cyclases catalyze the formation of cGMP from GTP. This family of enzymes includes soluble (sGC) and particulate guanylyl cyclases (pGC). The sGC are heterodimers containing one active catalytic site and one inactive pseudo-site. They are activated by nitric oxide. The pGC are homodimers whose activity is notably regulated by peptide binding to the extracellular domain and by ATP binding to the intracellular kinase homology domain (KHD). The catalytic mechanism of the pGC is still not well understood. Homology modeling of the structure of the homodimeric guanylyl cyclase domain, based on the crystal structure of adenylyl cyclase, suggests the existence of two functional sites for the substrate GTP. We used a purified and fully active recombinant catalytic domain from mammalian pGC, to document its enzyme kinetics properties in the absence of the KHD. The enzyme presents positive cooperativity with the substrate Mg-GTP. However, a heterodimeric catalytic domain mutant (GC-HET) containing only one active catalytic site is non-cooperative and is more similar to sGC. Structure-activity studies of purine nucleoside analogs indicate that 2'd3'GMP is the most potent inhibitor of pGC tested. It displays mixed non-competitive inhibition properties that are potentiated by the second catalytic product inorganic pyrophosphate (PPi). It appears to be equivalent to purinergic site (P-site) inhibitors characterized on particulate adenylyl cyclase. Inhibition of pGC by 2'd3'GMP in the presence of PPi is accompanied by a loss of cooperative enzyme kinetics. These results are best explained by an allosteric dimer model with positive cooperativity for both the substrate and inhibitors.     

房间隔缺损患者行经封堵术后右心室容量及血浆心钠素的变化

目的:观察房间隔缺损(ASD)封堵术后右心室容量及血浆心钠素(ANP)的变化。方法:对23例成功行经导管ASD封堵术的患者,分别于封堵术前、术后3天取静脉血,采用放射免疫法测定血浆ANP浓度;并于术前、术后3天行心脏三维超声心动图检查,测量右心室腔容量;并对ANP与肺动脉压(PAP)、右心室腔容量、右室射血分数进行相关分析。结果:ASD封堵术后3天血浆ANP浓度较术前明显降低(101.89±35.80ng/Lvs153.46±74.55ng/L,P<0.01);封堵术后3天右心室容量较术前明显缩小,差异有统计学意义(P<0.05),相关分析显示:ASD患者血浆ANP浓度与PAP(r=0.74)、右心室舒张末期容量(r=0.50)、收缩末期容量(r=0.50)分别呈正相关(P均<0.05)、与右室射血分数呈负相关(r=-0.38,P<0.05)。结论:ASD封堵术后血浆心钠素浓度明显降低,右心室腔明显缩小。     

基于ANP的医疗信息化人才评价指标体系研究

医疗行业信息化在计算机技术高速发展的今天显得尤为重要,其专业人才的培养已成为当务之急。本文通过分析医疗信息化人才的现状,应用网络分析法(ANP)建立了医疗信息化人才评价指标体系模型,分析了应用ANP方法评价指标体系的步骤,并在SuperDecisions软件中对所建立的医疗信息化人才评价指标体系的ANP模型进行了求解。