Hemodynamic effects of propranolol with spironolactone in patients with variceal bleeds: A randomized controlled trial

AIM: To study the hemodynamic effects of spironolactone with propranolol vs propranolol alone in the secondary prophylaxis of variceal bleeding. METHODS: Thirty-five cirrhotics with variceal bleeding randomly received propranolol (n = 17: Group A) or spironolactone plus propranolol (n = 18: Group B). Hemodynamic assessment was performed at baseline and on the eighth day. RESULTS: Spironolactone with propranolol caused a greater reduction in the hepatic venous pressure gradient than propranolol alone (26.94% vs 10.2%; P < 0.01). Fourteen out of eighteen patients on the combination treatment had a reduction in hepatic venous pressure gradient to ≤ 12 mmHg or a 20% reduction from baseline in contrast to only six out of seventeen (6/17) on propranolol alone (P < 0.05). CONCLUSION: Spironolactone with propranolol results in a better response with a greater reduction in hepatic venous pressure gradient in the secondary prophylaxis of variceal bleeding. A greater number of patients may be protected by this combination therapy than by propranolol alone. Hence, this combination may be recommended for secondary prophylaxis in patients with variceal bleeding.

Effect of spironolactone on cardiac remodeling after acute myocardial infarction

BACKGROUND:Few studies have reported the effect of aldosterone receptor antagonist(ARA) on myocardial remodeling after acute myocardial infarction(AMI).This study was undertaken to investigate the preventive effect of ARA on myocardial remodeling after AMI.METHODS:A total of 616 patients who had been admitted into the CCU of the First Affiliated Hospital of Harbin Medical University from January 2008 to January 2010 were studied prospectively.Only 528 patients were observed completely,including 266 of the control group and 262 of the treatment group.There was no statistical difference in age,gender,medical history,admission situation,and treatment between the two groups(P>0.05).The preventive effects of spironolactone on cardiac remodeling,left ventricular function,renal function and blood levels of potassium were evaluated by echocardiography,serum potassium and serum creatinine at one-month and one-year follow-up.RESULTS:The echocardiography indicators such as LVESD,LVEDD,LVEF,LAD-ML and LADSI were significantly improved in the treatment group compared with the control group at one year(P<0.05).In the treatment group,LVESD,LVEDD,LVPWT,LVEF,LAD-ML and LAD-SI were more significantly improved at one year than one month(P<0.05,P=0.007 to LVEF),and in the control group LVEF was more significantly improved at one year than one month(P=0.0277).There were no significant differences in serum potassium and serum creatinine levels between the two groups.CONCLUSION:On the basis of conventional treatment,the early combination of low-dose spironolactone(20 mg/d) could inhibit cardiac remodeling at late stage and prevent heart fadure.

Co-amorphous solid dispersion systems of lacidipine-spironolactone with improved dissolution rate and enhanced physical stability

Co-amorphous solid dispersion(C-ASD)systems have attracted great attention to improve the solubility of poorly soluble drugs,but the selection of an appropriate stabilizer to stabilize amorphous forms is still a huge challenge.Herein,C-ASD system of two clinical combined used drugs(lacidipine(LCDP)and spironolactone(SPL))as stabilizers to each other,was prepared by solvent evaporation method.The effects of variation in molar ratio of LCDP and SPL(3:1,1:1,1:3,1:6,and 1:9)on the drug release characteristics were explored.Polarized light microscopy(PLM),powder X-ray diffraction(PXRD),differential scanning calorimetry(DSC)and thermogravimetric analysis(TGA)were employed to evaluate the solid states.Prepared C-ASDs were further studied for their stability under the high humidity(RH 92.5%).Further analysis of C-ASDs via Fourier-transform infrared spectroscopy(FTIR)and Raman spectroscopy confirmed that hydrogen bond interactions between the two drugs played a significant role in maintaining the stability of the C-ASDs systems.Moreover,molecular dynamic(MD)simulations provided a clear insight into the stability mechanism at the molecular level.This study demonstrated the novel drug-drug C-ASDs systems is a promising formulation strategy for improved dissolution rate and enhanced physical stability of poorly soluble drugs.

Clinical research of fenofibrate and spironolactone for acute central serous chorioretinopathy

AIM：To compare the effectiveness of combined fenofibrate and spironolactone with fenofibrate alone for treatment of central serous chorioretinopathy（CSCR）.METHODS： Totally 60 patients（60 eyes） with a history of acute CSCR were randomed into two groups： group A with combination of fenofibrate（200 mg） and spironolactone（100 mg）,and group B with only fenofibrate（200 mg）.They were taken half an hour before meals and once per day for 8wk.The changes of the visual acuity,subjective symptom,ocular surface disease index（OSDI）,the tear film and optical coherence tomography were observed at 2,4,6,and 8wk before and after treatment.RESULTS： The best corrected visual acuity（BCVA,log MAR） was improved to 0.22 and 0.27 after treatment from baseline of 0.35 and 0.36 in groups A and B（P 〈0.05）,respectively.After 8wk treatment,the central subfield thickness（CST）,and subretinal fluid volumn（SFV） decreased significantly to 49.5% and 78.8% in group A,37.0% and 57.2% in group B.There were significant differences of CST and SFV in both groups（all P 〈0.05）.CONCLUSION：Fenofibratecombinedwithspironolactone may have more clinical efficacy in the treatment of CSCR than fenofibrate only.

Study the Effect of Spironolactone in Airway Resistance with Impulse Oscillometry in Patients with Congestive Heart Failure

Background: CHF (Congestive Heart Failure) is one of the most important causes of mortality and morbidity in the world. Diuretics such as spironolactone can decrease pulmonary congestion and reduce the amount of fibrosis in CHF patients. The goal was to assess whether spironolactone can decrease air way resistance and can we follow up the effect of diuretic therapy in patients of heart failure quantitatively by means of impulse oscillometry. Methods: It was clinical trial which performed in Ahvaz teaching hospital. 24 patients with congestive heart failure (CHF) which was classified as functional class II-IV and had EF Result: The age of patient was 61 ± 10 and the age of control was 57 ± 7 years old. The data of oscillometry before and after spironolactone were X5 (&minus;0.14 ± 0.05 vs &minus;0.14 ± 0.05, P: 0.93), R5 (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35), X20 (&minus;0.04 ± 0.06 vs &minus;0.06 ± 0.06, P: 0.37), R20 (0.04 ± 0.03 vs 0.06 ± 0.06, P: 0.37), Zrs (0.39 ± 0.21 vs 0.39 ± 0.15, P: 0.35). Conclusion: There was a trend toward reduction of peripheral airway resistances in CHF patients than controls with use of 1 month of spironolactone. Although there was not significant change in the number of X5, R5, X20, R20 occurred the trend toward reduction of number triggers the point that oscillometry can be used for quantitative follow up of CHF patients.

Analysis of spironolactone residues in industrial wastewater and in drug formulations by cathodic stripping voltammetry

The redox behavior of spironolactone（SP） drug in Britton-Robinson（BR） buffer of pH 2-11 was investigated by differential pulse cathodic stripping voltammetry（DPCSV） and cyclic voltammetry（CV） at hanging mercury dropping electrode（HMDE）.At pH 9-10.5,the DPCSV of SP drug showed two cathodic peaks at1.15 and1.38 V at the HMDE vs.Ag/AgCl reference electrode.In the CV,at pH 9-10,the dependence of the cathodic peak current,Ip,c and peak potential,Ep,c of the second peak（Ep,c2） on the scan rate（n） and on the depolizer（SP） concentrations was typical of an electrode coupled（EC） chemical reaction type mechanism.The plot of Ip,cat 1.380 V of the DPCSV vs.SP concentration at pH 9 was linear over the concentration range of 1.2×1010-9.6×107 M.The lower limit of detection（LLOD） and limit of quantification（LOQ） of the drug were 1.1×1011 and 4.14×1011 M,respectively.The method was successfully applied for the analysis of SP residues in industrial wastewater,in pure form（98.273.1%） and in drug formulations e.g.Aldactones tablet（98.3572.9%）.The method was validated by comparison with HPLC and the official data methods.

Application Effect Evaluation of Telmisartan combined with Spironolactone after Catheter Ablation of Patients with Paroxysmal Atrial Fibrillation

Objective:To evaluate the application effect of telmisartan combined with spironolactone after catheter ablation of patients with paroxysmal atrial fibrillation.Methods:80 cases of patients with paroxysmal atrial fibrillation who received radiofrequency catheter ablation treatment from March 2013 to March 2016 in our hospital were randomly selected,these patients were divided into two groups according to the treatment methods,namely,the telmisartan with Spironolactone treatment group(combined treatment group,n=40)and the conventional therapy group(n=40).The hs-CRP,NT-proBNP,LAD and recurrence of the two groups were analyzed.Results:The hs-CRP,NT-proBNP levels after 3 months of the combined treatment group were significantly lower(P<0.05),the recurrence rate 10.0%(4/40)was significantly lower than the conventional therapy group 27.5%(11/40)(P<0.05),the time to recurrence was significantly longer than the conventional therapy group(P<0.05).Conclusion:The application effects of telmisartan combined with spironolactone after catheter ablation in the treatment of patients with paroxysmal atrial fibrillation are better than conventional therapy.

Dapagliflozin and Spironolactone Improved Clinical Symptoms and CV Outcomes in Patient with HF Preserved Ejection Fraction (HFpEF) in Hard-to-Reach Rural African Population: A Case Series

Objective: To observe the benefit of mineralocorticoid receptor antagonist and sodium-glucose co-transport 2 inhibitor (SGLT2 inhibitor) in heart failure preserved ejection (HFpEF) in rural Tanzania. Background and Result: The use of spironolactone and dapagliflozin was shown to be effective in improving the clinical outcome and reducing CV hospitalization rate and CV mortality in patients with heart failure preserved left ventricular ejection fraction (HFpEF). This is the case presentation of one patient with HFpEF with diastolic dysfunction grade 3, obesity grade 3, Type 2 Diabetes, and Atrial Fibrillation (permanent). In the case of a 76-year-old female after previous ineffective treatment, the initiation of Spironolactone and Dapagliflozin led to a rapid and marked improvement in the clinical conditions. Diastolic dysfunction was improved from stage III to stage I. Moreover, the initiation of spironolactone and dapagliflozin therapy avoided a referral for surgical intervention and interrupted a long series of hospitalizations for acute HF and prevented CV death. Conclusion: Based on our experience, we conclude that the treatment with spironolactone and dapagliflozin allows for better treatment optimization with a positive impact on the control of clinical outcomes and preventing CV death and CV hospitalization in HFpEF and related comorbidities in the African population, which is underrepresented in most of the trials.

The Effect of Spironolactone Loading on the Properties of 3D-Printed Polycaprolactone/Gold Nanoparticles Composite Scaffolds for Myocardial Tissue Engineering

Engineered cardiac constructs(ECC)aid in the progression of regenerative medicine,disease modeling and targeted drug delivery to adjust and aim the release of remedial combination as well as decrease the side effects of drugs.In this research,polycaprolactone/gold nanoparticles(PCL/GNPs)three-dimensional(3D)composite scaffolds were manufactured by 3D printing using the fused deposition modeling(FDM)method and then coated with gelatin/spironolactone(GEL/SPL).Scanning electron microscopy(SEM)and Fourier transform-infrared spectroscopy(FTIR–ATR)were applied to characterize the samples.Furthermore,drug release,biodegradation,behavior of the myoblasts(H9C2)cell line,and cytotoxicity of the 3D scaffolds were evaluated.The microstructural observation of the scaffolds reported interconnected pores with 150–300µm in diameter.The 3D scaffolds were degraded significantly after 28 days of immersion in stimulated body fluid(SBF),with the maximum rate of GEL-coated 3D scaffolds.SPL release from cross-linked GEL coating demonstrated the excess of drug release over time,and according to the control release systems,the drug delivery systems(DDS)went into balance after the 14th day.In addition,cell culture study showed that with the addition of GNPs,the proliferation of(H9C2)was enhanced,and with GEL/SPL coating the cell attachment and viability were improved significantly.These findings suggested that PCL/GNPs 3D scaffolds coated with GEL/SPL can be an appropriate choice for myocardial tissue engineering.

Effects of spironolactone on electrical and structural remodeling of atrium in congestive heart failure dogs

Background Renin-angiotensin-aldosterone system has been demonstrated to be associated with both congestive heart failure （CHF） and atrial fibrillation （AF）. This study investigated the effects of spironolactone, a kind of aldosterone antagonist, on atrial electrical remodeling and fibrosis in CHF dogs induced by chronic rapid ventricular pacing. Methods Twenty one dogs were randomly divided into sham-operated group, control group, and spironolactone group. In control group and spironolactone group, dogs were ventricular paced at 220 beats per minute for 6 weeks. Additionally, spironolactone at 15 mg.kgl.d1 was given to dogs 1 week before rapid ventricular pacing until pacing stopped. Transthoracic and transoesophageal echocardiographic examinations were performed to detect structural and functional changes of the atrium. Swan2 Ganz floating catheters were used to measure hemadynamics variances. Atrial effective refractory period （AERP）, AERP dispersion （AERPd） conduction velocity （CV） were determined. The inducib atrial fibrosis was quantified with Masson staining. intra- and inter-atrium conduction time （CT） and intra-atrium ity and duration of AF were also measured in all groups. Finally, Results AERP did not change significantly after dogs were ventricular paced for 6 weeks. However, AERPd, intra- and inter-atrium CT increased significantly, and CV decreased apparently, which was negatively correlated to the atrial fibrosis （r=-0.74, P〈0.05）. Simultaneously, left atriums were enlarged and cardiac hemadynamics worsened in pacing dogs. Although spironolactone could not affect cardiac hemadynamics effectively, it can obviously improve left atrial ejection fraction （P〈0.05）. Spironolactone treatment did not alter AERP duration, but this medicine dramatically decreased AERPd （P〈0.05）, shortened intra- and inter-atrium conduction time （P〈0.05）, and increased atrium CV. Moreover, spironolactone decreased the inducibility and duration of AF （P〈0.05）, as well as atrial fibrosis （P〈0.01） induced by chronic rapid ventricular pacing. Conclusion Spironolactone contributes to AF prevention in congestive heart failure dogs induced by chronic rapid ventricular pacing, which is related to atrial fibrosis reduction and independent of hemadynamics.

Spironolactone in preventing hypokalemia following traumatic brain injury

Objective： Hypokalemia is a frequent complication observed after traumatic brain injury （TBI）.We evaluated the effect of spironolactone on preventing hypokalemia following moderate to severe TBI.Methods： Patients with moderate to severe TBI, whose Glasgow Coma Scale （GCS） scores of 9-12 and ＜9,respectively, were equally randomized into intervention and control groups, matching with severity of trauma and baseline serum level of potassium. For the intervention group, we administrated spironolactone （1 mg/kg per day）on the second day of admission or the first day of gavage tolerance and continued it for seven days. No additional intervention was done for controls. Hypokalemia （mild： 3-3.5 mg/L, moderate： 2.5-3 mg/L, and severe： ＜2.5 mg/L serum K＋） and other electrolyte abnormalities were compared between the two groups at the end of the intervention.Results： Sixty-eight patients （58 males and 10 females）were included with mean age=（33.1±11.8） years, and GCS=7.6±2.8. The two groups were similar in baseline characteristics.Patients who received spironolactone were significantly less likely to experience mild, moderate, or severe hypokalemia （8.8%, 2.9%, and 0） compared with controls （29.4%, 11.7%,and 2.9%, respectively, P＜0.05）. No significant difference was observed between the two groups in the occurrence of other electrolyte abnormalities, hyperglycemia or oliguria.Conclusion： Spironolactone within the first week of head injury could prevent the occurrence of late hypokalemia with no severe side effects.

Effect of Treatment of Rosacea in Females by Chibixiao Recipe (赤鼻消方) in Combination with Minocycline and Spironolactone

To observe the clinical efficacy of Chibixiao Recipe （赤鼻消方, CBX） in combination with minocycline and spironolactone in treating rosacea in females. Methods： Sixty-eight women with rosacea were randomly assigned to the treated group （48 cases） and the control group （20 cases）, both of which were treated with minocycline and spironolactone taken orally, but to the treated group, the Chinese herbal recipe, CBX was given additionally. Besides, cryotherapy with liquid nitrogen was applied to those with apparent capillary dilatation. The therapeutic course for both groups was 8 weeks. The levels of serum testosterone before and after treatment were determined by radioimmunoassay （RIA）, and a 4-month followup was conducted. Results： In the treated group the cure-markedly effective rate was 87.5% and the recurrent rate was 6.5 %, while in the control group, they were 45.0 % and 41.2 % respectively. Comparisons in the indexes between the two groups all showed significant difference （both P〈0. 01 ）, with the cure-markedly effective rate higher, and the recurrent rate lower in the treated group. The serum level of testosterone got lowered in both groups （ P〈0. 05 and P〈0. 01 ）, but the lowering in the treated group was more significant, showing significance when compared with that in the control group （ P〈0. 01 ）. Conclusion： CBX in combination with Western medicine has effect in treating rosacea superior to that of Western medicine alone, and could effectively reduce recurrent rate and the serum level of testosterone.

The effect of spironolactone on the levels of GATA4 protein and hypoxia inducible factor-1α in patients receiving coronary stent implantation

In the present study,we aimed to explore the protective effect of spironolactone on cardiac function in patients undergoing coronary stent implantation by determining the serum levels of GATA4 and hypoxia-inducible factor-1α(HIF-1α)proteins before and after the coronary stent implantation.A total of 134 patients undergoing coronary stent implantation in our hospital from March 2019 to March 2020 were retrospectively selected using the propensity score matching(PSM)method.Of the 134 patients,67 patients taking spironolactone were used as a test group,and the other 67 patients without taking spironolactone were used as a control group.In all patients,the levels of serum GATA4,HIF-1α,and troponin I proteins were determined before as well as 24 h and 6 months after the coronary stent implantation.Left ventricular ejection fraction(LVEF)and left ventricular systolic global longitudinal strain(GLS)were determined before and 6 months after the coronary stent implantation.There were no significant differences in the HIF-1αlevel between the two groups before and 6 months after the operation,while the HIF-1αlevel was significantly lower in the test group compared with the control group at 24 h after the operation(P<0.01).There were no significant differences in the GATA4 protein level between the two groups before and 24 h after the operation,while the GATA4 protein level was significantly lower in the test group compared with the control group at 6 months after the operation(P<0.01).There was no significant difference in LVEF between the two groups before and 6 months after the operation.GLS was significantly improved at 6 months after the operation compared with that before the operation in both groups,while GLS was significantly better in the test group compared with the control group at 6 months after the operation(P<0.01).Collectively,spironolactone could protect cardiac function probably by improving myocardial hypoxia and inhibiting myocardial remodeling.

COMBINED THERAPY OF CAPTOPRIL AND SPIRONOLACTONE FOR REFRACTORY CONGESTIVE HEART FAILURE

It is traditionally considered that angiotensin-converting enzyme inhibitor(ACEI) and spironolactone could not be used simultaneously because of the assumed risk of hyperkalemia.

Sequential Combination Diuretic-Therapy for Massive Fluid Overload in Furosemide-Refractory Patients with Diabetic Kidney Disease

Patients with renal disease are at risk of fluid overload which escalates as the disease progresses. In the present study, we evaluated the efficacy of sequential combination diuretic-therapy (SCDT) in management of massive fluid overload in Furosemide-refractory renal patients. The added diuretics were Spironolactone 25 mg daily for 3 days, to those without risk of hyperkalemia, followed by Hydrochlorothiazide 25 mg/Metolazone 5 mg daily for 3 more days. Excluded patients were those with 1) acute renal disease, 2) echocardiographic evidence of: a) left ventricular ejection fraction < 40%, b) significant stenotic or incompetent valvular disease, c) ASD or VSD, d) significant pericardial disease, and 3) significant limb venous disease or on drugs likely to cause limb-oedema. To assess the extent of fluid overload;clinical examination was complemented with radiological imaging as well as echocardiographic measurement of systolic pulmonary arterial pressure (sPAP). SCDT led to significant symptomatic, clinical, and radiological improvement of fluid overload without significant side effects. The latter were limited to hyperkalemia and hyponatremia which improved with dietary compliance. Moreover, hyperkalemia improved after subsequent addition of Thiazide/Metolazone. SCDT led to significant (p < 0.001) increase in fractional excretion of sodium and decrease in body weight and sPAP. In conclusion;SCDT is a safe and efficacious measure to control fluid overload in patients with renal diseases.

Combination Therapy to Treat Asian Female Pattern Hair Loss

Background: Hair loss in women has a various psychosocial impact and effective treatments have been required. Camouflaging products which cover exposed areas on the scalp and hide visible hair loss are common, but medical therapies for female pattern hair loss (FPHL) are not so common. We have treated patients with FPHL using our combination therapy that consists of oral spironolactone, oral and topical minoxidil, and an injectable treatment for six years. Methods: 4568 female patients were treated between the years 2013 and 2018. Our combination therapy consists of 25 mg oral spironolactone once daily, 2.5 mg oral and 5% solution topical minoxidil twice daily, and an injectable treatment once monthly for 6 - 12 months. Digital photographs were taken pre- and post-treatment, and patient assessments were recorded after 6 and 12 months post-treatment. Results: Significant improvement was observed compared to the pre-treatment for all patients in the digital photographs. 95% and 96% of patients reported satisfaction with the results of the treatment after 6 and 12 months post-treatment, respectively. Minor complications were observed in a total of 223 (4.9%) patients, characterized by slight pain and bleeding due to injection, slight palpitation, swelling, hair growth in undesirable areas, headache, dizziness, itching. The seminor complications resolved spontaneously. No treatment-related adverse events were observed. Conclusion: A combination of these therapeutic options offers rapid and highly efficacious treatment for FPHL with minimal complications, and is recommended as an effective treatment for FPHL.

Immobility Responses Affected by Potassium in Old Rats

Four immobility responses (IR): elicited by clamping, bandaging, grasping and inversion, and their modification by potassium and spironolactone was studied in old Wistar rats (body weight, 500 g). When undrugged, only clamping and grasping, but not bandaging and inversion induced an IR in rats. Potassium and spironolactone significantly enhanced the duration of IR induced by clamping but not by grasping. They also induced an immobility response by bandaging, but not by inversion. The data suggest that IR induced by clamping and bandaging are somehow related to changes in the potassium serum levels. Consequently, such a relationship may be a suitable model to study some forms of paralysis in human beings which are related to changes in the potassium serum levels.