Fosinopril Research Articles

Mechanisms of Chinese herbs combined with ischemic postconditioning in protecting myocardium of rats from ischemia-reperfusion injury

To observe the effects of Chinese patent medicines with the function of replenishing qi to activate blood (RQAB) plus ischemic postconditioning (IPoC) in protecting myocardium of rats from ischemia-reperfusion (I/R) injury, and to explore the possible mechanisms. Seventy-five Sprague-Dawley rats were randomly divided into sham-operated group (the suture was penetrated around the left anterior descending coronary artery, but not tied, n=15), I/R group (30 minutes of in situ transient occlusion of the left anterior descending artery, followed by 1 hour of reperfusion, n=15), IPoC group (30 minutes occlusion of the left anterior descending artery, followed by 3 cycles of 10 s of reperfusion/10 s of ischemia before 1-hour reperfusion, n=15), RQAB plus IPoC group (pretreated with 0.162 g/kg Xinyue Capsule and 0.135 g/kg Xiongshao Capsule for 14 days, and treated with IPoC 2 h after the final gavage, n=15), fosinopril sodium plus IPoC group (pretreated with fosinopril sodium, 0.9 mg/kg, n=15). Serum creatine kinase-MB (CK-MB) activity and cardiac troponin T (cTnT) level were detected; myocardial infarction size was measured by nitrotetrazolium blue chloride staining; Toll-like receptor 2 (TLR2) and TLR4 in myocardial tissue were examined by immunohistochemical method; interleukin-1beta (IL-1beta) and interleukin-6 (IL-6) levels in myocardial tissue were examined by enzyme-linked immunosorbant assay. Compared with the I/R group, myocardial enzymes and infarction size were decreased significantly in the IPoC group (P<0.01); expressions of TLR2 and TLR4 and levels of IL-1beta and IL-6 in myocardial tissues were also significantly lower than those in the I/R group (P<0.05). Compared with the fosinopril sodium plus IPoC group, expressions of TLR2 and TLR4 were decreased significantly in the RQAB plus IPoC group (P<0.05, P<0.01). Compared with IPoC, RQAB plus IPoC reduced the infarction size and the release of myocardial enzyme CK-MB (P<0.01), and decreased the expressions of TLR2 and TLR4 and the levels of IL-1beta and IL-6 (P<0.05, P<0.01) in myocardial tissues. Pretreatment with Chinese herbs for nourishing qi and activating blood circulation can enhance the protective effect of IPoC on rat myocardial I/R injury, and its mechanism may be related to inhibition of TLR expression and expressions of the downstream proinflammatory cytokines.

Effect of atragalus membranaceus combined fosinopril on NF- κB activity and OPN expression in overload albumine stimulating proximal tubular cells

Objective To explore whether or not the function of atragalus membranaceus combined fosinopril on decreasing NF- κB activity and OPN expression in overload albumin stimulating proximal tubuler cells. Methods Cultured cells without stimulation were used as placebo. Cultured cells were incubated with bovine serum albumin fat acid free (BSA) 20mg/ml as the control. Cultured cells were incubated with fosinopril for different hours as the treatment. Cultured cells were incubated with atragalus membranaceus combined fosinopril for different hours as the atragalus membranaceus group. ELISA and RT-PCR were used to observe NF -κB activity and OPN expression after cultured for 12h, 24h. Result Atragalus membranaceus combined fosinopril rapidly decreased NFκB activity and OPN expression. Compared with the other groups, the difference was significant. Conclusion Astragalus membranaceus combined fosinopril can obviously decrease NFκB activity and OPN expression in overload albumine stimulating proximal tubular cells. Key words: Astragalus membranaceus △/TU; Fosinopril/TU; Albumins/PD; Kidney tubules; NF-kappa B/ME; Sialoglycop-roteins/ME

Effects of renin-angiotensin system inhibitors on density of rat myocardial, pericardial, and pulmonary mast cells in experimental heart failure

The activation of the renin-angiotensin system (RAS) plays a critical role in the pathogenesis of car- diac failures (CFs). Using a model of experimental CFs, we studied the effects of lisinopril (LP) and fosinopril (FP) (inhibitors of the angiotensin-converting enzyme), as well as of losartan (LT, antagonist of angiotensin II receptors), on the density of multifunctional mast cells (MCs). RAS inhibitors were injected for 4 weeks begin- ning 4 weeks after two (with 24-h intervals) isoproterenol injections. MCs of different degrees of maturity were identified in paraffin sections stained with Alcian blue and Safranin. The CF severity was estimated based on functional echocardiogram parameters and on morphological criteria in histological sections. The MC density in the myocardiums of intact rats, as well as of rats with CFs that were and were not treated with drugs was relatively low, i.e., 3-4 cells/mm 2 . The MC density in pericardiums of intact rats was several times higher than in myocardiums, i.e., 35 ± 7 cells/mm 2 . In CFs, the density of pericardial MCs was 1.7 higher than in intact rats due to an increase in the density of immature cells stained with Alcian blue ( p < 0.05). Injections of LP increased the MC density 1.4-fold due to the density of mature cells stained with Safranin ( p < 0.01). Injections of FP and LT did not affect the MC density and the balance of cells of different degrees of maturity in the peri- cardium. In lungs, 96-99% of MCs were Alcian positive. In intact rats, rats with CF, and rats with CF treated with FP, the density of these cells was 30 cells/mm 2 . Injections of LP and LT decreased the density of pulmo- nary MCs to 7 cells/mm 2 ( p < 0.01) and 19 cells/mm 2 ( p < 0.05), respectively. The functional parameters of the heart were consistent with the data of the morphological analysis. The improvement of myocardial function was only noted in rats with CF treated with FP and LT. The obtained data show that, in the myocardiums, pericar- diums, and lungs of rats with CF, reaction of MCs (as the cell elements of the RAS tissue) to injections of inhib- itors of RAS was diverse. In the pericardium, injections of LP stimulated the maturation of resident MCs, as well as the replenishment of the population at the expense of immature cells that migrate from outside (by means of the migration of immature cells from the outside). This allows us to suggest us that the secretory activ- ity of these cells is intensified. Conversely, in lungs, injections of LP, like of LT, suppress the MC population.

Clinical observation on the effects of valsartan combined with fosinopril in patients with IgA.nephropathy

Objective To observe the effect and safety of valsartan combined with fosinopril on patients with IgA nephropathy.Methods 91 patients were assigned to three groups:conventional therapy group ( n=28),fosinopril group (n=31),and combined therapy group ( n = 32).Six months were as one therapeutic course.Urine protein,blood pressure and serum creatinine were detected during trial period.Results After six months of therapy,the level of 24hours proteinuria of all groups were decreased,especially in combined group (P＜0.05).The total effective rate was 84.38 % in combined therapy group,61.29% in fosinopril group,and 35.71% in conventional therapy group,Conclusion It is safe and effective to treat lgA nephropathy with angiotensin receptor antagonist combined with angiotensin converting enzyme inhibitor.It is superior to simple angiotensin converting enzyme inhibitor administration or conventional therapy. Key words: Fosinopril; Valsartan ; IgA nephropathy

Effects of Qufeng Tongluo Recipe on proliferation of and TGF-β1 and IL-6 mRNA expressions in glomerular mesangial cells from rats

To investigate the effects of Qufeng Tongluo Recipe (QFTLR), a compound of traditional Chinese herbal medicine for dispelling wind and removing obstruction in the meridians, on cell proliferation and expressions of transforming growth factor-beta1 (TGF-beta1) and interleukin-6 (IL-6) mRNAs induced by lippolysaccharide in glomerular mesangial cells from rats. The method of serum pharmacology was used. A total of 32 rats were divided into normal control group, untreated group, QFTLR group and positive control group which also was named Monopril (fosinopril sodium) group. Mesangial proliferative glomerulonephritis was induced by injection of antithymocyte serum in the rats except for the normal control group. Sera of the rats were obtained after corresponding interventions. Lipopolysaccharide-induced proliferation of rat mesangial cells (MCs) cultured in the respective serum-containing media was detected by the method of methyl thiazolyl tetrazolium (MTT) assay, and the expressions of TGF-beta1 and IL-6 mRNAs were analyzed by the method of reverse transcription polymerase chain reaction. Compared with the untreated group, QFTLR showed remarkable inhibitory function on the proliferation of the mesangial cells (P<0.05). The expressions of TGF-beta1 mRNA in mesangial cells were increased in the untreated group, QFTLR group and Monopril group when compared with the normal control group (P<0.01), but the TGF-beta1 mRNA expressions in QFTLR group and in Monopril group were lower than that in the untreated group. The IL-6 mRNA expression could be increased by the LPS stimulation, and it was significantly higher in the other three groups than that in the normal control group, including the untreated group, the Monopril group and the QFTLR group (P<0.01). Compared with the untreated group, the expression of IL-6 mRNA was decreased by QFTLR and Monopril (P<0.01). QFTLR was better than Monopril in inhibiting the proliferation of the mesangial cells and decreasing the expressions of TGF-beta1 and IL-6 mRNAs (P<0.05). QFTLR has great inhibitory effect on mesangial cell proliferation and expressions of TGF-beta1 and IL-6 mRNAs, which may be one of its mechanisms in postponing glomerular sclerosis.

Chromatographic Behavior of Fosinopril Sodium and Fosinoprilat Using Neural Networks

In this paper, the chromatographic characterization of fosinopril sodium and fosinoprilat is presented. The first stept was pKa determination for the active substance and its degradation product using RP-LC. It was followed by optimization employing the combination of experimental design and artificial neural networks. For the definition of input and output variables, the central composite design for three factors was built. Back propagation algorithm was applied to model the system, and then the optimization of the experimental conditions was carried out in the neural network with 3-8-2 structure, which confirmed to be able to provide the maximum performance. From the method optimization, the most appropriate experimental conditions for fosinopril sodium and fosinoprilat analysis were extracted. The optimized method was validated and applied in the quality control of tablets and for forced degradation studies.

Monitoring of fosinopril sodium impurities by liquid chromatography–mass spectrometry including the neural networks in method evaluation

In this paper, the mass spectrometry (MS) detection has been applied for screening of fosinopril sodium impurities which arise during forced stress study. Before MS analysis, liquid chromatographic method with suitable mobile phase composition was developed. The separation was done on SunFire 100 mm × 4.6 mm 3.5 μm particle size column. The mobile phases which consisted of methanol–ammonium acetate buffer–acetic acid, in different ratios, were used in a preliminary study. Flow rate was 0.3 mL min −1. Under these conditions, percent of methanol, concentration of ammonium acetate buffer and acetic acid content were tested simultaneously applying central composite design (CCD) and artificial neural network (ANN). The combinations of experimental design (ED) and ANN present powerful technique in method optimization. Input and output variables from CCD were used for network training, verification and testing. Multiple layer perceptron (MLP) with back propagation (BP) algorithm was chosen for network training. When the optimal neural topology was selected, network was trained by adjusting strength of connections between neurons in order to adapt the outputs of whole network to be closer to the desired outputs, or to minimize the sum of the squared errors. From the method optimization the following mobile phase composition was selected as appropriate: methanol–10 mM ammonium acetate buffer–acidic acid (80:19.5:0.5 v/v/v). This mobile phase was used as inlet for MS. According to molecular structure and literature data, electrospray positive ion mode was applied for analysis of fosinopril sodium and its impurities. The proposed method could be used for screening of fosinopril sodium impurities in bulk and pharmaceuticals, as well as for tracking the degradation under stress conditions.

Chinese herbal formula Qilong‐Lishui granule improves puromycin aminonucleoside‐induced renal injury through regulation of bone morphogenetic proteins

The Chinese herbal formula Qilong-Lishui granule (QLG) is an effective natural product for treatment of renal disorder. It was composed of six Chinese herbs according to our clinical practice in the treatment of patients with kidney disease. However, molecular and cellular mechanisms of QLG are still unclear. Therefore, the objective of the current study is to investigate molecular and cellular mechanisms of QLG in puromycin aminonucleoside (PAN)-induced nephrotic syndrome. Wistar rats were divided into six groups of sham operation, PAN model, PAN model with high-dosage QLG (QLG-H), PAN model with median-dosage QLG (QLG-M), PAN model with low-dosage QLG (QLG-L), and PAN model with fosinopril (FP). The PAN model was induced by jugular vein injection of PAN at a dose of 5 mg/100 g body weight. Quantities of 24 h urinary protein excretion were examined on days 5, 10, 15, 20, 25 and 30. All rats were sacrificed on day 31 for blood biochemistry, kidney histology and reverse transcriptase-polymerase chain reaction analysis. PAN-induced nephrotic syndrome was successfully produced in rats. Treatment of QLG significantly reduced protein excretion and blood urea nitrogen and creatinine. QLG and FP treatments also improved protein content in blood, and reduced total cholesterol and triglyceride in blood. Moreover, QLG and FP improved the damage of interstitial induced by PAN. Furthermore, CYP and FP were able to reverse BMPRII and Smad1 mRNAs abundance caused by PAN. QLG attenuates PAN-induced kidney injury possibly through the bone morphogenetic protein signal transduction pathway.

Study on the relativity of optimal time to take fosinopril

目的 研究2种服药时间对血压的影响.方法 随机将42例服用长效降压药的高血压患者分为2组.对照组采用传统方法,即进餐后半小时服药.观察组采用清晨起床后空腹服药.2组患者均在6:00、8:00、14:00、18:00、22:00、2:00进行血压测量.结果 2组总的降压疗效无显著性差异(P＞0.05),但在控制清晨高血压的疗效上,观察组优越于对照组(P＜0.05).结论 选择最佳服药时间,对降压非常有意义。

Therapeutic conversion from fosinopril to benazepril at a Veterans Affairs medical center

On July 1, 2004, fosinopril sodium became the angiotensin-converting-enzyme (ACE) inhibitor of choice at the San Diego Veterans Affairs Healthcare System (VAHS). Problems arose when the drug’s manufacturer decreased fosinopril’s production, as the drug’s patent was nearing expiration. The

Spectrophotometric analysis of fosinopril sodium in pure form and tablets

Simple UV and third derivative spectrophotometric methods in methanol have been developed for the determination of fosinopril sodium in bulk drug and its pharmaceutical formulations. The simple UV spectrum of fosinopril sodium in methanol exhibits absorption maxima (λmax) at 208 nm, whereas in the third derivative spectrum the maxima occur at 217.4 nm and the minima at 223 nm. Both the methods were found to be simple, economical, accurate, reproducible and can be adopted in routine analysis of fosinopril sodium in bulk drug and in tablet dosage form.

Microemulsion liquid chromatographic method for characterisation of fosinopril sodium and fosinoprilat separation with chemometrical support

The properties of the eluent are the essential factors governing the efficiency in the high-performance liquid chromatography (HPLC) method. A novel approach in retention modelling in the liquid chromatographic separation of fosinopril sodium and its degradation product, fosinoprilat, applying a microemulsion as the mobile phase, was used. The modifications of the mobile phase included the changes to the type of the lipophilic phase, the type and concentration of co-surfactant and surfactant, as well as the pH of the mobile phase. In this study, a full factorial 2(3) design, as the optimal method for screening of the experiment, was applied for selecting factors which had an influence on separation. Optimisation was done by a central composite design. An appropriate resolution with reasonable retention times was obtained with a microemulsion containing 0.9% w/w of cyclohexane, 2.2% w/w of sodium dodecyl sulphate (SDS), 8.0% w/w of n-butanol and 88.9% of aqueous 25 mM disodium phosphate, the pH of which was adjusted to 2.8 with 85% orthophosphoric acid. Separations were performed on an X-Terra 50-mmx4.6-mm, 3.5-mum particle size column at 30 degrees C. UV detection was performed at 220 nm and with a flow rate of 0.3 mL min(-1). The established method was validated and applied for analysis of appropriate tablets. The proposed chromatographic procedure for the separation of fosinopril sodium and its degradation product is less expensive compared with the conventional reversed-phase HPLC method, as well as being simple and rapid. The optimised and validated method can be used for separation, identification and simultaneous determination of fosinopril sodium and fosinoprilat in bulk drug and in pharmaceutical dose forms.

Development of liquid chromatographic method for fosinoprilat determination in human plasma using microemulsion as eluent

Fosinopril sodium presents a prodrug for the active angiotensin converting enzyme (ACE) inhibitor, fosinoprilat. The dual elimination of fosinoprilat by the liver and the kidney distinguishes fosinopril from other angiotensin converting enzyme inhibitors. Such ways of elimination are important for antihypertensive therapy of patients on haemodialysis. The paper presents development and evaluation of a new and sensitive liquid chromatographic (LC) method for the analysis of fosinoprilat in plasma obtained from patients on haemodialysis. A microemulsion system mixture as mobile phase has been used for the separation and analysis of fosinoprilat in plasma samples. The plasma samples were injected directly onto the HPLC system (Waters Breeze) after appropriate sample dilution with mobile phase. Separations were performed on the Bakerbond ENV 4.6 mm × 150 mm, 5 μm particle size column with UV detection at 220 nm. The flow rate was 1.00 mL min −1. The mobile phase consisted of 1.0% (w/v) of diisopropyl ether, 2.0% (w/v) of sodium dodecyl sulphate (SDS), 6.0% (w/v) of n-propanol and 91% (w/v) of aqueous 25 mM di-sodium hydrogen phosphate, pH adjusted to 2.8 with 85% orthophosphoric acid. The developed method was then subjected to method validation according to the criteria stated in the FDA bioanalytical method validation guidance. The results for specificity, linearity, low limit of quantification (LLOQ), precision, accuracy and stability were within the accepted criteria. The unique approach applied in this paper makes possible the determination of fosinoprilat even in the presence of metabolites of other drugs, so the method can be used for obtaining the reliable results in a fast and simple way.

Rotational Brightness Modulation and Starspots on the RS CVn-type Stars IN Com, IL Com, UX Ari, and V711 Tau

UBVRI photometric observations and models of spotting are presented for four noneclipsing RS CVn systems: IN Com (G5III/IV), IL Com (F8V+F8V), UX Ari (K01V+G5V), and V711 Tau (K1IV+G5V). A low amplitude variability caused by cold (ΔT=1700K)spots which can occupy up to 19% of the star's surface is confirmed for the little-studied star IL Com. Long-term light curves are constructed and the stellar magnitudes and color indices of the unspotted photospheres are estimated for IN com, UX Ari, and V711 Tau. It is shown that UX Ari becomes bluer with decreasing brightness, so its variability cannot be fully explained in terms of cold spots. Models of spotting on In Com and V711 Tau are constructed from the full set of available photometric observations. The spots on both of these variables lie at middle latitudes and occupy up to 22% (In Com) and 33% (V711 Tau) of the stars' surfaces. Both stars manifest a tendency for the width of the spots to decrease as their area increases. This is a crude analog of the Maunder butterflies. These stars experience cyclical spot activity and have a differential rotation of the type found on the sun.

Chemometrical Approach in Fosinopril-Sodium and its Degradation Product Fosinoprilat Analysis

In this paper the experimental design has been applied to define the optimum chromatographic conditions for the separation of fosinopril sodium and its degradation product, fosinoprilat. Fosinopril is a prodrug and after being hydrolysed, it becomes an active drug fosinoprilat. For experimental screening full factorial design 23 was applied. Methanol content, pH of the mobile phase and column temperature were independent variables or factors to be investigated in two levels - »low« and »high«. Capacity and selectivity factors were chosen as dependent variables and matrix was applied to estimate coefficients of the linear model. After experimental screening, RSM (response surface methodology) was applied for optimization. Optimum conditions were: X Terra™ 150 mm × 4.6 mm, 5 μm particle column at 45 °C; methanol-water (75 : 25 v/v) at pH 3.1 as a mobile phase, with a flow rate of 1 mL min−1. UV detection was performed at 220 nm. Propylparaben was used as an internal standard. The proposed method is rapid, accurate, selective and because of its sensitivity and reproducibility, it may be used for the quantitative analysis of fosinopril sodium and its degradation product in Monopril® tablets. Recovery values for fosinopril sodium were between 101.6% and 102.9% and content of degradation product fosinoprilat was lower than 5%. Applying the chemometrical approach enables a relatively limited number of experiments to define factors which affect the chromatographic behavior of investigated substances and obtain optimum conditions for their analysis.

Effects of low-dose treatment with felodipine versus fosinopril in Chinese patients with nonischemic heart failure and normal blood pressure: A double-blind, randomized, crossover study

Background: Two second-generation calcium channel blockers, felodipine and amlodipine besylate, have been associated with similar high mortality rates in patients with ischemic heart failure (HF) but not in patients with nonischemic causes of HF. In patients with nonischemic HF, amlodipine might have a beneficial effect on survival. However, no difference in mortality rates was found between felodipine and placebo in a nonischemic HF group. Felodipine 10 mg/d was used in 1 large study, a dose considered high for nonischemic HF usually associated with normal blood pressure (BP). Objective: The aim of this study was to compare the effects of 12-week, low-dose treatment with felodipine versus those of an angiotensin-converting enzyme inhibitor, fosinopril sodium, in patients with nonischemic HF and normal BP. Methods: This double-blind, randomized, crossover trial was conducted at Taipei Medical University Hospital (Taipei, Taiwan). Patients aged ≥ 18 years with angiographically proved, nonischemic HF and normal BP who were being treated with an optimal regimen of digitalis and diuretics were enrolled. After a 2-week run-in period, patients were randomized to first receive 12 weeks of treatment with felodipine tablets (2.5 mg/d) or fosinopril tablets (7.5 mg/d) and, after a 2-week washout period, were crossed over to the opposite treatment. Efficacy analysis was performed before (baseline) and after treatment and included symptomatic assessment using a 7-grade clinical scale; 2-dimensional echocardiography (2-D echo); exercise tests; and neurohumoral data, including plasma renin activity, plasma aldosterone, and 24-hour urinary epinephrine (E) and norepinephrine (NE) measurements. The primary end point was death due to HF, and the secondary end point was hospital admission due to worsening HF. Compliance was measured using a pill count at the end of each treatment period. Results: We enrolled 33 patients. One developed worsening HF during the run-in period and was admitted. A total of 32 patients entered the study (18 men, 14 women; mean [SD] age, 48.2 [6.3] years [range, 34–56 years]; mean [SD] systolic BP, 117.2 [9.8] mm Hg [range, 100–138 mm Hg]; mean [SD] diastolic BP, 59.4 [5.7] mm Hg [range, 50–72 mm Hg]). No hospital admission or cardiac death due to HF occurred during 12 weeks of treatment. Twenty-seven patients were included in the felodipine assessment, and 30 patients were included in the fosinopril assessment. Significant improvement in clinical score was noted in both treatment groups (both P < 0.01). The clinical scores did not differ significantly between the 2 treatments. No significant differences were found in 2-D echo parameters between treatments or within groups after treatment versus baseline. Significant improvement in exercise duration was noted with both study drugs after treatment versus baseline (both P < 0.01). No significant difference in exercise duration was found between the 2 treatments. Urinary E and NE were not significantly different between treatments or after treatment with either study drug compared with baseline. Conclusion: The present findings suggest that, in Chinese patients with moderate to severe HF who have normal BP and insignificant coronary artery disease and were being treated with diuretics and digitalis, a 12-week, low-dose course of felodipine (2.5 mg/d) as a vasodilator was associated with as satisfactory an outcome as standard treatment with fosinopril (7.5 mg/d).

Conformational study of fosinopril sodium in solution using NMR and molecular modeling

AbstractTwo conformers of fosinopril sodium in methanol were unambiguously established using 2D NMR methods and variable‐temperature NMR experiments. Differences in their conformational structure were shown to be related to the rotational energy barrier about the amide bond and hydrophobic interaction. The relationship between the 3D structure and activity is discussed. It is suggested that the trans‐conformer may be more biologically active owing to its stacking structure and strong hydrophobic interaction and the cis‐conformer could be more easily hydrolyzed because of its extended structure. Copyright © 2003 John Wiley &amp; Sons, Ltd.

Novel flow injection spectrophotometric determination of fosinopril using UV-assisted digestion and an orthophosphates calibration graph

This work describes the first flow injection (FI) method for the spectrophotometric determination of the anti-hypertension drug fosinopril (FSP), a phosphorus-containing compound. The method is based on the UV-assisted digestion of the analyte using ammonium peroxodisulfate as the oxidizing reagent. The yielded orthophosphate ions are determined by a rapid and robust FI method employing the molybdenum blue approach. The time needed for complete conversion of a maximum FSP amount concentration of 2.0×10 −4 mol l −1 was 30 min. Based on the capability of the home-made UV digester used in this work to process eight samples simultaneously, an acceptable samples analysis frequency of 16 h −1 was achieved. Additionally, a very important advantage of the proposed method is that an orthophosphate ions calibration graph can be used instead of FSP, as 100% conversion of FSP was achieved. Quantitative measurements of FSP were made in the range 1.0×10 −6 to 2.0×10 −4 mol l −1. The application of the developed FI method to the analysis of two commercially available pharmaceutical formulations produced accurate results, as the relative errors were <1.5% in both cases, compared to the labeled values.

AACN Synergy Model for Patient Care

within the walls of the hospital setting. Today’s healthcare environment mandates that patients with serious diseases live in their homes, causing the need for acute and critical care settings to reach out to their patients not only to assist them in maintaining a quality of life but also to decrease costs of hospital readmissions. This situation is especially true for patients with chronic heart failure (CHF). In the United States, many patients with CHF regularly visit CHF clinics that are run by advanced practice nurses; these clinics assist patients with maintaining and often improving their state of heart failure, while also proving cost-effective. The Synergy Model provides the framework for nurses to manage complex clients experiencing acute exasperation of their illness and to work toward reducing the trajectory of the illness. The purpose of this article is to discuss the application of The Synergy Model to an ambulatory CHF clinic. We will discuss the characteristics of a patient who visited a local clinic, with the advanced practice nurse holding a Authors

Regression of ventricular and vascular hypertrophy: are there differences between structurally different angiotensin-converting enzyme inhibitors?

It is well established that angiotensin-converting enzyme (ACE) inhibitors (ACEI) reduce blood pressure (BP) and hypertrophy of the left ventricle and vessels. The aim of our study was to compare chemically different ACEIs regarding their ability to modulate left ventricular and media hypertrophy, ACE activity and plasma endothelin-1 concentrations in spontaneously hypertensive rats (SHRs). After establishing equi-effective dose regimes, SHRs were treated (3 months) with captopril, enalapril, fosinopril or ramipril (2 x 25, 10, 20 or 1 mg/kg per day or corresponding 1% doses for studying blood pressure-independent effects). Systolic blood pressure was reduced in SHRs receiving high doses of captopril, enalapril, fosinopril or ramipril (-61, -54, -35 and -47 mmHg), whereas low doses were ineffective. Left ventricular weight was decreased in animals treated with high doses (captopril/enalapril/fosinopril/ramipril: -17/-19/-17/-19%), but not low doses of agents. Media thickness of thoracal aorta was reduced by administering high doses (captopril/enalapril/fosinopril/ramipril: -31/-32/-27/-26%) and low doses (-16/-22/-22/-19%) of agents. ACE activity was reduced in heart, aorta and kidney of rats treated with high and low doses of all ACE inhibitors, whereby high doses showed more pronounced effects. Plasma endothelin-1 concentrations were not altered. A blood-pressure-ineffective treatment with an AT -antagonist revealed similar effects on cardiovascular hypertrophy. ACEIs reduce cardiovascular hypertrophy uniformly via an AT -receptor- mediated mechanism, reinforcing the opinion that ACEI effects are indeed class effects. The significance of local renin-angiotensin systems was confirmed by antihypertrophic effects in the aorta that were apparent in the absence of any blood pressure reduction.