Evaluation of quinapril on regional blood flow and cardiac function in patients with congestive heart failure.

Quinapril, a nonsulfhydryl ACE inhibitor, was evaluated in ten New York Heart Association (NYHA) functional class (FC) II-III CHF patients to determine its effects on regional blood flow [effective renal plasma flow (ERPF), renal blood flow (RBF), renal vascular resistance (RVR), hepatic blood flow (HBF), hepatic vascular resistance (HVR), segmental limb pressure (SLP), creatinine clearance (CRCL)] and cardiac function [left ventricular ejection fraction (LVEF)]. Previous vasodilator therapy was withdrawn 2 weeks before baseline measurements. Stable regimens of digoxin and diuretics were continued throughout the study. ERPF was assessed using p-aminohippurate (PAH), HBF by indocyanine green (ICG) clearance, and LVEF by radionuclide scintography. Segmental limb pressures were measured by Doppler flow detection. Measurements were performed at baseline (B) and after 4 weeks of quinapril therapy (10 mg BID). Quinapril increased renal (P less than 0.05) and hepatic blood flow (P = 0.06) and significantly reduced renal and hepatic vascular resistance. Glomerular filtration rate and left ventricular ejection fraction were unchanged. Mean arterial pressure and brachial segmental pressures decreased without change in heart rate. Noninvasive cardiovascular assessments indicate that quinapril improves regional blood flow while exhibiting no change in left ventricular ejection fraction, in patients with NYHA FC II-III CHF.     

坎地沙坦对慢性心力衰竭患者脑钠肽水平及心功能的影响

目的探讨坎地沙坦对慢性心力衰竭(CHF)患者脑钠肽(BNP)水平和心功能的影响。方法已接受常规治疗,按照纽约心脏病协会(NYHA)分级标准,心功能3～4级的CHF患者80例,随机分为2组:治疗组40例,对照组40例。治疗组在常规治疗基础上加用坎地沙坦8mg治疗12周。对比分析治疗前后两组患者的血浆BNP水平、NYHA分级、血压、超声心动图等指标。结果治疗组较对照组左室舒张末期内径(LVEDd)[(61±6)mmvs.(57±5)mm]、左室收缩末期内径(LVESd)[(51±7)mmvs.(45±4)mm]显著下降(P均<0.05),左室射血分数(LVEF)显著升高[(40±10)%vs.(48±7)%](P<0.05),血浆BNP[(131±52)ng/Lvs.(71±8)ng/L]显著降低(P<0.05);此外,坎地沙坦治疗前后,患者血浆BNP降低值与左室舒张末期内径(r=0.80)、左室收缩末期内径(r=0.79)减少呈正相关(P均<0.01),而与LVEF的增加呈负相关(r=-0.86,P<0.01)。结论坎地沙坦治疗充血性心力衰竭(CHF)的总有效率达92%以上,坎地沙坦能阻断CHF的发展进程,改善心功能及降低血清BNP水平,血浆BNP可作为评价血管紧张素Ⅱ受体拮抗剂治疗CHF的监测指标之一。     

手持式微型电动负压吸引器在危重病人院内转运过程中的应用

目的 观察手持式微型电动负压吸引器在危重病人院内转运过程中的应用效果及安全性。方法 纳入2021年8月至2022年6月江苏省中医院重症监护室（ICU）需院内转运的气管插管或气管切开病人106例。按照随机数字表法分为对照组（转运过程中以50 mL注射器连接无菌吸痰管吸痰）和观察组（使用手持式微型电动负压吸引器吸痰）各53例。观察两组转运开始前和转运结束后病人呼吸频率、氧合指数（P/F）、血氧饱和度、收缩压、舒张压和心率的差异。结果 转运开始前，两组呼吸频率、P/F、血氧饱和度、收缩压、舒张压和心率比较，均差异无统计学意义（P>0.05）。转运结束后，观察组呼吸频率[（18.43±4.81）次/分比（20.60±4.45）次/分]、收缩压[（129.09±18.27）mmHg比（139.81±17.30）mmHg]和心率[（81.75±19.33）次/分比（91.43±15.07）次/分]均明显低于对照组（P<0.001），而血氧饱和度[（97.64±2.36）%比（95.98±1.43）%]明显高于对照组（P<0.001）。在转运前后差值方面，观察组呼吸频率、P/F、血...     

ACE Inhibitors in Heart Failure-Switching from Enalapril to Perindopril

Summary

Although ACE inhibitors have demonstrated their beneficial effects in heart failure, whether different agents may induce different benefits remains unclear. We designed an open, sequential, prospective study switching heart failure patients receiving enalapril to perindopril which has been reported to be longer acting and better tolerated. The objective of the study was to find out if clinical and functional status could be further improved by changing from enalapril 30?mg daily to a perindopril 4mg daily.

Assessments of clinical status, echo-cardiography and nuclear ventriculography were performed at baseline under enalapril (30mg mean dose (b.i.d.)), then 6 and 12 months after the switch to perindopril (4mg/day mean dose).

Thirty-one patients were included (90% men, aged 56.5?±?11.8 years, mean radionuclide left ventricular (LV) ejection fraction 22.4?±?8.5%). After 6 months of treatment, NYHA functional class was significantly improved; the percentage of patients in class I increased to 57% after perindopril versus 20% at baseline (p?<?0.001), and 50% of the total study population gained at least one NYHA class. After 12 months of treatment, 80% of the patients were in NYHA class I. Blood pressure decreased significantly with a good tolerance at 6 months and then remained stable. After 12 months of treatment, significant reductions of LV end-diastolic diameter (61.4?±?5.3 vs. 64.5?±?6.5mm; p?=?0.001) and LV mass index (143.3?±?21.5 vs. 164.2?±?40.2g/m²; p?<?0.001) were observed, reflecting a positive effect on the LV remodelling process.

Despite some limitations, because it is of an open-label design with a small number of patients, our study found significant differences in clinical and objective parameters in heart failure patients switched from enalapril to perindopril. The prognostic significance of these findings remains to be investigated.     

Inhibition of pulmonary endothelial angiotensin converting enzyme activity by trandolaprilat in vivo

The purpose of the present study was to contrast a commonly used ACE inhibitor (enalaprilat) with a novel ACE inhibitor (trandolaprilat) in their ability to inhibit 1) pulmonary capillary endothelial-bound ACE activity in vivo, 2) arterial pressure responses to i.v. angiotensin I and bradykinin, and 3) selected tissue ACE activity ex vivo, in rabbits. Pulmonary capillary endothelium-bound ACE activity in vivo was estimated via the single pass transpulmonary hydrolysis of the substrate ³H-Benzoyl-Phenylalanyl-Alanyl-Proline (BPAP). Doses of acutely administered trandolaprilat (8 μg/kg) or enalaprilat (10 μg/kg) were equieffective in reducing the pressor response to angiotensin I. At these doses, trandolaprilat produced a greater inhibition of pulmonary capillary endothelial-bound ACE activity (66.5 ± 4.7% reduction of baseline BPAP metabolism vs. 52.7 ± 4.2% by enalaprilat, P < 0.05). Chronically administered trandolaprilat (8 μkg/day for 8 days) was more effective than enalaprilat (either 8 μg/kg/day or 10 μg/kg/day for 8 days) in reducing the angiotensin-1 induced increase in mean arterial pressure (increases of 9.7 ± 1.4 mmHg vs. 20.3 ± 2.3 mmHg and 19.1 ± 5.7 mmHg respectively; P < 0.01), as well as in reducing BPAP metabolism. In agreement with in vivo data, trandolaprilat was 5.5-, 3.6-, and 2.5-times more effective than enalaprilat in reducing ACE activities in the aorta, left ventricle, and lung, respectively. We conclude that trandolaprilat is a more potent, longer acting, and more tissue-selective ACE inhibitor than enalaprilat, and that the method outlined here can be used to aid in the development of tissue-specific ACE inhibitors. Drug Dev. Res. 41:22–30, 1997. © 1997 Wiley-Liss, Inc.     

Potential Angiotensin-Converting Enzyme Inhibitor—Epoetin Alfa Interaction in Patients Receiving Chronic Hemodialysis

We compared epoetin alfa (EPO) dose requirements and hematocrit response in 17 patients receiving chronic hemodialysis at baseline and after 3 and 12 months of therapy with angiotensin-converting enzyme (ACE) inhibitors (12 enalapril, 5 captopril). No acute processes were present (infection, hemorrhage, inflammation) at time of starting ACE inhibitor therapy. Mean (± SD) intravenous EPO dosages at zero, 3, and 12 months were 6012 ± 2575, 5800 ± 2026, and 5660 ± 2285 U 3 times/week (p=0.56), and mean differences were − 212 U for 0–3 months (95% CI −1310 to 886) and −713 U for 0–12 months (95% CI −2142 to 716). Mean ± SD hematocrits were 30.5 ± 3.9%, 31.6 ± 3.2%, and 34.2 ± 3.1% (p=0.01, zero vs 12 mo), and mean differences were 1.7% for 0–3 months (95% CI −1.41 to 4.81) and 3.85% for zero–12 months (95% CI 0.71–7). Our results indicate that ACE inhibitors do not increase EPO dose requirements or reduce hematocrits in these patients.     

Antihypertensive efficacy of indapamide SR in hypertensive patients uncontrolled with a background therapy: the NATIVE study*

ABSTRACT

Objectives: Antihypertensive monotherapy rarely achieves blood pressure (BP) control. NATIVE (NATrilix SR use in combInation antihypertensiVe thErapy) evaluated indapamide sustained release (SR) in hypertensive patients receiving background therapy.

Research design and methods: Patients remaining hypertensive (systolic BP [SBP], 145–180?mmHg; diastolic BP [DBP], 95–105?mmHg) while receiving an angiotensin-converting enzyme (ACE) inhibitor (n = 709), β-blocker (n = 629), calcium-channel blocker (CCB; n = 493), angiotensin II type 1 receptor blocker (ARB; n = 75), α-blocker (n = 29) or other therapy (n = 6) were enrolled, recruited by physicians from 228 centres in Pakistan. Indapamide SR 1.5?mg was administered daily for 3 months with background therapy. BP was assessed every 2 weeks, and blood glucose and total cholesterol were evaluated at baseline and study end in a patient subgroup. Adverse events were also recorded.

Main outcome measures and results: Of 2073 enrolled patients (49% males; mean age 51 years), 1941 received indapamide SR and background therapy. SBP and DBP decreased significantly (SBP, 166 ± 16?mmHg at baseline vs. 132 ± 12?mmHg at 3 months; DBP, 102 ± 8?mmHg vs. 83 ± 6?mmHg; both p < 0.0001 vs. baseline). Patients uncontrolled with an ACE inhibitor, β-blocker, CCB or ARB achieved an SBP/DBP decrease of 34 ± 15/19 ± 9, 33 ± 17/19 ± 10, 33 ± 15/18 ± 8 or 35 ± 16/20 ± 12?mmHg, respectively (all p < 0.0001). In all, 84% of patients achieved target SBP (≤?140?mmHg) and 61% achieved BP normalisation (SBP <?140, DBP <?90?mmHg). The absence of placebo control may lead to an overestimation of the extent of the BP reduction achieved. Glucose and cholesterol levels were unaffected by indapamide SR. Four percent of patients experienced side-effects, which were mild-to-moderate in severity.

Conclusions: In patients with hypertension despite antihypertensive therapy, indapamide SR significantly reduced BP with a good acceptability profile. Indapamide SR may represent an effective additional therapy for patients who do not achieve BP goals with other antihypertensive agents.     

Subsensitivity of the failing human heart to isoprenaline and milrinone is related to beta-adrenoceptor downregulation

The number of cardiac beta-adrenoceptors and the positive inotropic effect of isoprenaline and milrinone were measured in cardiac membranes and isolated, electrically driven muscle strips from nonfailing donor hearts and from patients with mitral valve disease (NYHA II-III), ischemic heart disease, and dilated cardiomyopathy (NYHA IV). In nonfailing hearts, the number of beta-adrenoceptors were 41.5 fmol/mg protein (mean, n = 3). In ischemic heart disease and NYHA II-III, there was a loss of cardiac beta-adrenoceptors (22.1 fmol/mg protein, mean, n = 3; 23.2 +/- 2.7 fmol/mg protein, n = 30), respectively. In NYHA IV, there was a pronounced reduction of the number of cardiac beta-adrenoceptors to 12.1 +/- 1.5 fmol/mg protein (n = 15). The Kd value did not differ in either group. Correspondingly, the positive inotropic effect of isoprenaline was more pronounced in nonfailing myocardium, reduced in NYHA II-III and ischemic heart disease and almost blunted in NYHA IV. Similar results were observed with the phosphodiesterase inhibitor milrinone. A good correlation of the beta-adrenoceptor density to the maximal positive inotropic effect of isoprenaline and milrinone was observed. Neither the number of cardiac beta-adrenoceptors nor the positive inotropic effect of isoprenaline correlated with the age of the patients. We conclude that the number of cardiac beta-adrenoceptors and the positive inotropic effect of beta-adrenoceptor agonists are reduced in the failing human heart depending on the severity of heart failure. Furthermore, the positive inotropic effect of milrinone is also reduced and related to the reduction of beta-adrenoceptors. The lack of correlation with the age of the patients provides evidence for a predominant role of heart disease rather than aging in the reduction of beta-adrenoceptors and subsensitivity to cyclic AMP-increasing positive inotropic agents in the failing human heart.     

地佐辛复合右美托咪定在清醒患者纤维支气管镜气管插管术中的应用

目的 探讨地佐辛复合右美托咪定在重症医学科清醒患者纤维支气管镜气管插管术中的镇痛镇静效果及安全性.方法 将本科2015年1月至2016年12月180例需行气管插管机械通气的清醒患者采用随机数字表法分为A、B、C三组,各60例.A组静脉泵注咪达唑仑0.1 mg/kg;B组静脉泵注地佐辛0.1 mg/kg+咪达唑仑0.05 mg/kg;C组静脉泵注地佐辛0.1 mg/kg+右美托咪定1μg/kg.观察并比较插管前(T1)、插管时(T2)、插管后10 min(T3)患者心率(HR)、呼吸频率(RR)、平均动脉压(MAP)、指端血氧饱和度(SpO2)以及插管过程中患者躁动情况(MAAS评分)、气管插管后10 min患者的镇静效果(Ramsay评分)、转入时疾病严重程度评分(APACHEⅡ评分).结果 3组T3时间点HR均较T1时间点显著下降[A组:(99.0±5.2)次/min比(101.2±7.6)次/min,P＜0.05;B组:(97.3±6.1)次/min比(103.0±9.5)次/min,P＜0.05;C组:(94.4±7.2)次/min比(100.0±8.8)次/min,P＜0.05].3组RR在T2时间点均较同组T1时间点显著下降[A组:(27.1±2.6)次/min比(28.5±3.6)次/min,P＜0.05;B组:(26.3±2.8)次/min比(28.1±3.3)次/min,P＜0.05;C组:(25.1±3.5)次/min比(27.6±3.1)次/min,P＜0.05].B组T3时间点MAP较同组T1、T2时间点下降[(71.2±8.8) mmHg(1 mmHg=0.133 kPa)比(74.3±8.0) mmHg,P＜0.05;(71.2±8.8) mmHg比(74.3±8.8) mmHg,P＜0.05].C组T2时间点MAP较同组T1、T3时间点下降[(68.4±8.1) mmHg比(73.2±6.3),P＜0.05;(68.4±8.1) mmHg比(72.8±7.6) mmHg,P＜0.05].T1时间点,3组HR、RR、MAP差异无统计学意义(均P＞0.05).T2时间点,C组MAP较A、B两组显著下降[(68.4±8.1)mmHg比(73.6±8.6),P＜0.05;(68.4±8.1) mmHg比(74.3±8.8) mmHg,P＜0.05].T3时间点,C组HR较A、B两组显著下降[(94.4±7.2)次/min比(99.0±5.2)次/min,P＜0.05;(94.4±7.2)次/min比(97.3±6.1)次/min,P＜0.05].插管过程中B、C两组MAAS评分均显著低于A组[(3.2±1.0)比(3.9±1.0),P＜ 0.05;(3.0±1.0)比(3.9±1.0),P＜0.05],但B、C组间差异无统计学意义(P＞0.05).气管插管后10 min,A组Ramsay评分显著低于B、C两组[(2.4±0.9)比(2.7±0.9),P＜0.05;(2.4±0.9)比(2.8±0.9),P＜0.05],但B、C两组比较差异无统计学意义(P＞0.05).结论地佐辛复合咪达唑仑或右美托咪定较单纯使用咪达唑仑可显著改善清醒患者气管插管的耐受性并提高镇静效果;地佐辛复合右美托咪定用于清醒患者气管插管镇痛镇静效果确切.     

国产卡维地洛与美托乐尔治疗心力衰竭对心肺功能的影响

目的　对比观察卡维地洛和美托乐尔治疗慢性收缩性心力衰竭对心、肺功能的影响及其安全性。方法　将 34例在常规心力衰竭治疗 (利尿剂 +地高辛 +ACEI/AⅡ受体拮抗剂 )的基础上 ,心功能为Ⅱ～Ⅲ级及病情稳定的Ⅳ级非瓣膜病变慢性收缩性心力衰竭患者 ,随机分为卡维地洛组 (A组 )、美托乐尔组 (B组 )。采用小剂量逐渐递增给药 ,两组剂量分别为A组 :(2 1 3± 2 8)mg ;B组 :(65± 2 9)mg。治疗前及治疗后 3个月分别评定心功能级别 ,检查血、尿常规 ,血糖 ,血脂 ,肝、肾功能 ,电解质 ,超声心动图 ,气道激发试验以及 6min步行距离 ,并进行治疗前后及组间的对比。结果　两组患者经加用 β 受体阻滞剂 (β B)治疗 3个月后 ,心力衰竭症状、心功能分级、血流动力学指标、运动耐量均较用药前明显改善 ,且组间比较差异无显著性。美托乐尔较卡维地洛有较显著的降心率作用 ,卡维地洛虽增加气道阻力 ,但不足以影响气道的阻塞程度和肺的总通气功能。两药均增高甘油三酯 ,组间比较差异无显著性。未见两药对血细胞 ,电解质 ,肝、肾功能 ,血糖有影响。结论　卡维地洛和美托乐尔对治疗慢性收缩性心力衰竭均有较好疗效。     

Invasive Pharmacodynamic Characterization of Combined Ibopamine and Calcium Blocker Therapy for Heart Failure

Study Objective . To determine the acute hemodynamic response of single-dose coadministration of ibopamine plus nifedipine or diltiazem in patients with New York Heart Association functional class (NYHA FC) II—III congestive heart failure. Design . A single-blind, placebo-controlled, two-paired, crossover study. Setting . Cardiology clinics at two large teaching hospitals. Patients . Eight patients with NYHA FC II—III congestive heart failure who met the inclusion criteria were selected randomly. Interventions . All patients underwent right heart catheterization. Day 1 consisted of concomitant calcium channel blocker plus placebo, with cardiac and peripheral hemodynamic recordings from 30 minutes–24 hours. The design was equivalent on day 2, with single-dose administration of ibopamine plus calcium channel blocker. Measurements and Main Results . Single-dose nifedipine-diltiazem augmented cardiac output and stroke volume secondary to decreasing systemic vascular resistance. The nifedipine-ibopamine and diltiazem-ibopamine subgroups demonstrated relatively equal hemodynamics, augmenting cardiac index (nifedipine 43%, p<0.05; diltiazem 40%, p<0.05 vs baseline) while decreasing systemic vascular resistance (nifedipine 41%, p<0.05; diltiazem 28%, p NS vs baseline) 30 minutes after the dose. In contrast to single-dose diltiazem, the diltiazem-ibopamine subgroup exhibited an increased left ventricular filling pressure (122%, p<0.05 vs baseline) and mean pulmonary artery pressure (43%, p<0.05 vs baseline) at 30 minutes after the dose. One patient experienced a transient episode of chest pain associated with increased heart rate and blood pressure with diltiazem-ibopamine. Conclusion . Diltiazem and ibopamine should be coadministered with caution in patients with coronary artery disease and left ventricular dysfunction.     

The Cost Effectiveness and Cost Utility of Valsartan in Chronic Heart Failure Therapy in Italy

Objective

To evaluate the cost effectiveness and cost utility of the use of valsartan in addition to standard therapy for the treatment of patients with chronic heart failure with low left ventricular ejection fraction (LVEF).

Methods

The study was conducted by means of a cohort simulation based on a probabilistic Markov model and projecting the 23-month follow-up results of the Val-HeFT (Valsartan Heart Failure Trial) study over a 10-year time horizon. The model included four states (New York Heart Association [NYHA] classes II, III, IV, and death), and had a cycle duration of 1 month. Probabilistic simulations were performed using the WinBUGS software for Bayesian analysis. The distribution of patient parameters (sex, age, use of β-adrenoceptor antagonists, and ACE inhibitors) in the simulated population were derived from the Italian heart failure patient population. Individual mortality data were derived from general mortality data by multiplying by a NYHA state-specific relative risk, while the probability of changing NYHA class was taken from the Val-HeFT data. Costs (2007 values) were calculated from the perspective of the Italian Health Service (IHS) and included costs for drugs and heart failure hospitalizations. Quality-of-life (QOL) weights were obtained byusing published health-related QOL data for heart failure patients.A 3.5% annual discount rate was applied. Probabilistic sensitivity analysis was performed on each parameter using original-source 95% confidence interval (CI) values, or a ±10% range when 95% CI values were unavailable.

Results

For the 10-year time horizon, patients were estimated to live for an average of 2.3 years or 1.7 quality-adjusted life-years (QALYs), with slight increases in the valsartan group. In this group, hospitalizations for worsening heart failure were predicted to be significantly reduced and overall treatment costs per patient to decrease by about €550. In subgroup analyses, valsartan lost dominance in patients in NYHA II, and in those receiving β-adrenoceptor antagonists or ACE inhibitors; the mean incremental cost-utility ratio for these groups was 21 240, 129 200, and 36 500 €/QALY, respectively.

Conclusions

Valsartan in addition to standard therapy is predicted to dominate standard therapy alone in Italian patients with mild to severe heart failure and low LVEF. There are relevant differences among various patient subgroups, and valsartan is expected to be good value for money particularly in the treatment of the most severe and less intensively treated (no ACE inhibitors, no β-adrenoceptor antagonist) heart failure patients.     

俯卧位与改良平卧截石位下经皮肾镜术治疗肾结石时患者血流动力学及疗效对比研究

【】目的 对比研究俯卧位与改良平卧截石位下经皮肾镜术治疗肾结石时患者血流动力学及疗效。方法 选取收住的肾结石患者60例,随机分为改良平卧位组与俯卧位组各30例,分别在改良平卧位、俯卧位下手术,观察疗效,患者麻醉前30min(T0)、麻醉成功后(T1)、术中30min(T2)、拔管时(T3)等不同时点时心率、收缩压、舒张压、血氧饱和度(SpO₂)变化。结果 两组手术时间、术中出血量及术后住院时间比较差异无统计学意义(P>0.05),改良平卧位组、俯卧位组结石清除率分别为86.67%、90.00%,比较差异无统计学意义(P>0.05);两组患者T0、T1、T2、T3等不同时点时心率、收缩压、舒张压、SpO₂比较差异无统计学意义(P>0.05);两组高危患者T0时心率、收缩压、舒张压、SpO₂比较差异无统计学意义(P>0.05),T1、T2、T3时心率、收缩压、舒张压两组高危患者比较差异有统计学意义(P<0.05),T1、T2、T3时SpO₂两组高危患者比较差异无统计学意义(P>0.05)。结论 俯卧位与改良平卧截石位下经皮肾镜术治疗肾结石时疗效及血流动力学均无明显差别,但是高危患者采用改良平卧截石位下手术术中及拔管时血流动力学相对影响较小。     

Effect of the phosphodiesterase inhibitor UK 61260 on human myocardial inotropy and diastolic relaxation.

The phosphodiesterase inhibitor UK 61260 exhibits positive inotropic activity in animal studies and is under clinical investigation for treatment of congestive heart failure (CHF). We examined the lusitropic and inotropic responses to UK 61260 in electrically driven (1 Hz, 37 degrees C) human auricular trabeculae (AUT, aortocoronary bypass operation, nonfailing hearts, n = 13) and in papillary muscle strips (PAP) from moderately (New York Heart Association, NYHA II-III, mitral valve replacement, n = 6) and terminally (NYHA IV, heart transplantation, n = 7) failing human hearts. For comparison, we studied the effects of UK 61260 after prestimulation with forskolin (FOR 0.03 microM) and isoprenaline (ISO 0.03 microM), as well as the effects of milrinone (MIL 1-1,000 microM), ISO (0.01-10 microM), ouabain (OUA, 0.1 microM), and Ca2+ (1.8-15 mM) in failing human myocardium alone. UK 61260 increased force of contraction (FOC), peak rate of tension increase (+T) and decay (-T) significantly (p less than 0.01) in AUT but not in PAP of NYHA II-III and NYHA IV. Only after prestimulation (FOR and ISO), was UK 61260 effective in stimulating FOC in NYHA II-III and NYHA IV. UK 61260 increased (p less than 0.01) +T and -T, resulting in a shortening of twitch time. As judged from the EC50 values, UK 61260 increased FOC more potently than MIL. The effectiveness of OUA and Ca2+ in increasing developed tension in human failing myocardium was significantly higher as compared with UK 61260. We conclude that during stimulation of the cardiac beta-adrenoceptor-adenylate-cyclase system, UK 61260 increases myocardial systolic and diastolic function in failing human myocardium.(ABSTRACT TRUNCATED AT 250 WORDS)     

miR-373靶向调控同源异型盒基因 B3表达影响子宫内膜癌 Ishikawa细胞生物学特性的实验研究

目的 探讨微小RNA(miR)-373靶向调控同源异型盒基因B3(HOXB3)表达对子宫内膜癌Ishikawa细胞增殖、侵袭和凋亡的影响.方法 本研究起止时间为2018年2月至2019年6月,将体外培养的Ishikawa细胞分为抑制剂阴性对照(inhibitor-NC)组(转染inhibitor-NC)、miR-373抑制剂(inhibitor)组(转染miR-373 inhibitor)、miR-373 inhibitor+siNC组(共转染miR-373 in?hibitor和NC siRNA)和miR-373 inhibitor+siHOXB3组(共转染miR-373 inhibitor和HOXB3 siRNA),采用实时荧光定量PCR检测Ishikawa细胞中miR-373的表达,双荧光素酶报告基因实验检测miR-373和HOXB3的靶向关系,采用免疫印迹法检测Ishikawa细胞中HOXB3蛋白的表达,细胞计数(CCK-8)法、Transwell实验和膜联蛋白V-FITC(Annexin V-FITC)/碘化丙啶(PI)双染法检测各组细胞增殖、侵袭和凋亡能力.结果 HOXB3是miR-373的靶基因.与inhibitor-NC组相比,miR-373 inhibitor组、miR-373 inhib?itor+siNC组和miR-373 inhibitor+siHOXB3组细胞中miR-373表达水平[(1.00±0.11)比(0.32±0.02)/(0.36±0.03)/(0.34±0.03)]和细胞增殖活力[24 h(0.63±0.04)比(0.41±0.03)/(0.43±0.03)/(0.52±0.03);48 h(0.97±0.06)比(0.68±0.05)/(0.72±0.06)/(0.85±0.05);72 h(1.35±0.11)比(0.88±0.08)/(0.92±0.07)/(1.12±0.09)]、穿膜细胞数[(85.26±8.72)个比(37.64±2.85)个/(40.55±3.23)个/(61.38±3.64)个]均明显降低,而细胞凋亡率[(8.75±1.23)％比(25.64±3.38)％/(28.48±3.26)％/(14.25±2.02)％]和细胞中HOXB3蛋白的表达水平[(0.27±0.03)比(0.77±0.06)/(0.73±0.06)/(0.51±0.03)]均明显升高(P<0.05);且miR-373 inhibitor+siHOXB3组中各指标的变化强度明显低于miR-373 inhibitor组(P<0.05);而miR-373 inhibitor+siNC组和miR-373 inhibitor组之间无明显差异(P>0.05).结论 下调miR-373表达可通过靶向HOXB3抑制子宫内膜癌Ishikawa细胞增殖、侵袭并促进细胞凋亡.     

Bioavailability of Phenytoin Acid and Phenytoin Sodium with Enteral Feedings

Study Objective . To compare the absolute bioavailability of phenytoin (PHT) sodium solution and PHT acid suspension in healthy volunteers receiving continuously infused enteral feedings. Design . Randomized, open-label, single-dose, three-period crossover study. Setting . University clinical research center. Subjects . Ten healthy volunteers age 23–43 years. Interventions . The three phases of the study were separated by at least 7 days. During phase A, subjects received PHT sodium 435 mg intravenously over 30 minutes. During phases B and C, subjects had a nasogastric feeding tube placed through which PHT acid suspension 400 mg and PHT sodium solution 435 mg were administered, respectively. For phases B and C, continuous enteral feedings were given by feeding tube for 14 hours before and after the PHT dose. Blood samples were collected over 72 hours after each PHT dose, and the serum was analyzed for PHT. Measurements and Main Results . The rate and extent of PHT absorption and PHT pharmacokinetics were determined using an empirical quadratic function of time method. Bioavailability, rate of absorption, maximum concentration (C_max), and time to maximum concentration (T_max) were compared for the two enteral doses by paired Student's t test. There were no significant differences in bioavailability for PHT acid suspension and PHT sodium solution (0.88 ± 0.15 vs 0.91 ± 0.7, p=0.57, 90% CI −0.14–0.071). The C_max was greater (7.4 ± 0.9 mg/L vs 5.5 ± 1.7 mg/L, p=0.019) and T_max was less (2.5 ± 3.8 vs. 14.8 ± 11.2 hrs, p=0.004) for the sodium solution. The time to 50% fractional absorption (0.33 ± 0.08 vs 3.2 ± 2.4 hrs, p=0.004) and 90% fractional absorption (7.9 ± 6.2 vs 22.3 ± 17.2 hrs, p=0.021) was also significantly shorter for the sodium solution. Conclusion . The absolute bioavailability of the two dosage forms of PHT administered with concomitant enteral feedings were not significantly different, however, the absorption patterns were significantly different, with the sodium solution being more rapidly absorbed.     

尿钠肽检测评价药物对慢性充血性心力衰竭的治疗反应

目的评价药物治疗慢性充血性心力衰竭(CHF)中尿钠肽(BNP)检测的意义。方法选择CHF、心功能Ⅱ～Ⅲ级(NYHA分级)患者41例,年龄43～87岁,平均(63±12)岁。检测BNP后,将其分为常规治疗组21例(血管紧张素转换酶抑制剂或血管紧张素受体阻滞剂+利尿剂+地高辛),酒石酸美托洛尔组20例(常规治疗+酒石酸美托洛尔),并在治疗3个月后重复检测BNP。BNP采用荧光免疫法测定。结果心力衰竭得到有效治疗后,两组BNP均显著下降(P<0.01),但两组治疗3个月后的BNP值比较,差异有统计学意义(P<0.01),说明酒石酸美托洛尔组优于常规治疗组。结论BNP检测在评价慢性充血性心力衰竭的药物疗效中具有重要的应用价值。     

Alpha-adrenoceptors and alpha-adrenoceptor-mediated positive inotropic effects in failing human myocardium

Experiments were designed to characterize cardiac alpha-adrenoceptors and the alpha-adrenoceptor-mediated positive inotropic effects in human myocardial tissue from patients with moderate New York Heart Association (NYHA) class II-III and severe (NYHA class IV) heart failure. The number of cardiac alpha-adrenoceptors was low but similar in moderate and severe heart failure (NYHA class II-III: 6.7 +/- 0.8 fmol/mg protein 3H-prazosin bound, n = 12; NYHA class IV: 7.4 +/- 0.9 fmol/mg protein 3H-prazosin bound, n = 9; NS). Correspondingly, the alpha-adrenoceptor-mediated positive inotropic effect (phenylephrine in the presence of propranolol) did not significantly differ in both groups. In the same hearts, the number of beta-adrenoceptors was measured. The number of beta-adrenoceptors was significantly reduced in severe heart failure (NYHA class II-III: 22.0 +/- 1.5 fmol/mg protein 3H-CGP 12177 bound, n = 12; NYHA class IV: 11.9 +/- 0.8 fmol/mg protein 3H-CGP 12177 bound, n = 9; p less than 0.05). The positive inotropic effect of isoprenaline was significantly reduced in NYHA class IV. The positive inotropic effect of Ca2+ was similar in both groups. In conclusion, cardiac beta-adrenoceptors and the beta-adrenoceptor-mediated positive inotropic effects were reduced in severely failing myocardium. Cardiac alpha-adrenoceptors and the positive inotropic effect resulting from their stimulation is unchanged. Therefore, down regulation in response to increased sympathetic stimulation or a compensatory increase of alpha-adrenoceptors does obviously not occur in the human heart.(ABSTRACT TRUNCATED AT 250 WORDS)