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Aging Jun 2024This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia.... (Meta-Analysis)
Meta-Analysis
This meta-analysis aimed to describe the efficacy of bumetanide in improving infarct volume, brain edema, and behavioral outcomes in animal models of cerebral ischemia. Embase, PubMed and Web of Science databases were searched from their inception to February 2024 (INPLASY:202430023). Data on the animal species, stroke model, drug dose, time of treatment, method of administration, study quality, and outcomes were extracted and pooled in a meta-analysis. The combined standardized mean difference (SMD) or mean difference (MD) estimates and 95% confidence intervals (CIs) were calculated using random- or fixed-effects models. Thirteen eligible studies involving >200 animals fulfilled the inclusion criteria and were included in this meta-analysis. Meta-analyses demonstrated that bumetanide treatment significantly reduced cerebral infarct volume (SMD: -0.42; 95% CI: -0.75, -0.09; < 0.01; = 186 animals) and consistently relieved brain edema (SMD: -1.39; 95% CI: -2.06, -0.72; < 0.01; = 64 animals). Subgroup analyses demonstrated that bumetanide treatment reduced infarct volume in transient but not permanent cerebral ischemia models. When administered after the stroke, it was more effective than treatment initiation before the stroke. Eight studies assessed the effect of bumetanide on behavioral function and the results showed that bumetanide treatment significantly improved neurobehavioral deficits (SMD: -2.35; 95% CI: -2.72, -1.97; < 0.01; = 250 animals). We conclude that bumetanide appears to be effective in reducing infarct volume and brain edema and improving behavioral recovery in animal models of cerebral ischemia. This mechanism needs to be confirmed through further investigation.
Topics: Bumetanide; Animals; Ischemic Stroke; Disease Models, Animal; Brain Edema; Sodium Potassium Chloride Symporter Inhibitors; Neuroprotective Agents
PubMed: 38850525
DOI: 10.18632/aging.205910 -
Journal of Clinical Hypertension... Jun 2024The study aimed to investigate differences in hypertensive- and cardio-preventive pharmacotherapy depending on if patients with hypertension received lifestyle...
The study aimed to investigate differences in hypertensive- and cardio-preventive pharmacotherapy depending on if patients with hypertension received lifestyle counseling or not, including the difference between men and women. Data from the Region Stockholm VAL database was used to identify all patients with a hypertension diagnosis and had visited a primary health care center within the past five years. Data included registered diagnoses, pharmacotherapy, and codes for lifestyle counseling. Logistic regression adjusted for age and comorbidity (diabetes, stroke, coronary heart disease, atrial fibrillation, gout, obesity, heart failure) was used, presenting results as odds ratios (OR) with 99% confidence interval (CI). The study included 130,030 patients with hypertension; 63,402 men and 66,628 women. Patients receiving recommended lifestyle counseling were more frequently treated with three or more hypertensive drugs: women OR 1.38 (1.31, 1.45) and men = 1.36 (1.30, 1.43); certain drug classes: calcium antagonists: women 1.09 (1.04, 1.14) and men 1.11 (1.06, 1.16); thiazide diuretics: women 1.26 (1.20, 1.34) and men 1.25 (1.19, 1.32); and aldosterone antagonists: women 1.25 (1.12, 1.41) and men 1.49 (1.34, 1.65). Patients receiving recommended level of lifestyle counseling with concomitant coronary heart disease, atrial fibrillation, diabetes, or stroke were more frequently treated with statins than those who did not. Further, recommended lifestyle counseling was significantly associated with anticoagulant treatment in patients with atrial fibrillation. Lifestyle counseling according to recommendations in national guidelines was significantly associated with a more thorough pharmacological treatment of hypertension, statins, and antithrombotic drugs as well as anticoagulants, in both men and women.
PubMed: 38850281
DOI: 10.1111/jch.14852 -
The Journal of Pharmacology and... Jun 2024Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and...
Acute Kidney Injury (AKI) is characterized by an abrupt decline in kidney function and has been associated with excess risks of death, kidney disease progression, and cardiovascular events. The kidney has a high energetic demand with mitochondrial health being essential to renal function and damaged mitochondria has been reported across AKI subtypes. 5' adenosine monophosphate-activated protein kinase (AMPK) activation preserves cellular energetics through improvement of mitochondrial function and biogenesis when ATP levels are low such as under ischemia-induced AKI. We developed a selective potent small molecule pan AMPK activator, compound , and tested its ability to increase AMPK activity and preserve kidney function during ischemia/reperfusion injury in rats. A single administration of caused sustained activation of AMPK for at least 24 hours, protected against acute tubular necrosis, and reduced clinical markers of tubular injury such as NephroCheck and Fractional Excretion of Sodium (FENa). Reduction in plasma creatinine and increased Glomerular Filtration Rate (GFR) indicated preservation of kidney function. Surprisingly, we observed a strong diuretic effect of AMPK activation associated with natriuresis both with and without AKI. Our findings demonstrate that activation of AMPK leads to protection of tubular function under hypoxic/ischemic conditions which holds promise as a potential novel therapeutic approach for AKI. No approved pharmacological therapies currently exist for acute kidney injury. We developed Compound which dose-dependently activated AMPK in the kidney and protected kidney function and tubules after ischemic renal injury in the rat. This was accompanied by natriuresis in injured as well as uninjured rats.
PubMed: 38849142
DOI: 10.1124/jpet.124.002120 -
European Journal of Case Reports in... 2024Studies have shown major cardiovascular effects associated with ketamine use disorder including dose-dependent negative inotropic effects. Preoperative ketamine use has...
BACKGROUND
Studies have shown major cardiovascular effects associated with ketamine use disorder including dose-dependent negative inotropic effects. Preoperative ketamine use has been linked to ketamine-induced stress cardiomyopathy.
CASE PRESENTATION
A 28-year-old female with a history of recurrent cystitis and ketamine use disorder (twice weekly for 14 years) presented with bilateral lower extremity oedema and shortness of breath for 3 months. She was tachycardic with a troponin level of 0.07 ng/ml and a B-type natriuretic peptide (BNP) level of 2511 pg/ml. Electrocardiogram showed normal sinus rhythm and transthoracic echocardiography (TTE) showed left ventricular ejection fraction (EF) of 15%, dilated left ventricle, and severe tricuspid and mitral regurgitation. Computed tomography (CT) scan of the chest and abdomen showed bilateral pleural effusions with congestive hepatopathy and ascites. The patient was started on intravenous furosemide, metoprolol, and sacubitril/valsartan. Rheumatological workup including complement levels, and antinuclear anti-double-stranded DNA was negative. A repeat TTE 2 weeks later revealed an EF of 25% and moderate tricuspid regurgitation. Four months later, the EF was 54% with normal left ventricular cavity size.
CONCLUSION
Although ketamine use disorder is increasing, data on long-term side effects is minimal. Screening for ketamine use disorders should be considered in patients presenting with acute systolic heart failure. Long-term studies are needed to evaluate the benefits of adding ketamine screening to standard urine toxicology.
LEARNING POINTS
Ketamine use disorder can lead to severe cardiovascular complications, including acute systolic heart failure, likely due to its direct negative inotropic effects and dose-dependent impact on cardiac function.Clinicians should consider screening for ketamine use disorder in young adults presenting with acute systolic heart failure, especially when other common aetiologies have been ruled out.Early recognition and prompt treatment of ketamine-induced heart failure with diuretics and guideline-directed medical therapy can lead to significant improvement in cardiac function, but long-term management should also focus on ensuring cessation of ketamine use disorder.
PubMed: 38846645
DOI: 10.12890/2024_004470 -
Medecine Tropicale Et Sante... Mar 2024Reducing blood pressure after stroke is important to prevent recurrent stroke, but we have no data about the control of blood pressure in our context. The purpose of...
INTRODUCTION
Reducing blood pressure after stroke is important to prevent recurrent stroke, but we have no data about the control of blood pressure in our context. The purpose of this study was to assess management of hypertension among post-stroke patients in a neurology department.
METHOD
It was a retrospective study involving hypertensive stroke patients. They were followed up at 1, 3, 6 and 12 months after discharge.
RESULTS
141 patients fulfilled the inclusion criteria. The mean age was 61 years. Almost all patients (94.3%) received a dual antihypertensive therapy combining mainly an ACE inhibitor and a diuretic (70.2%). During follow-up, only 76 patients were assessed at M1, 50 at M3, 44 at M6 and 42 at M12. The average monthly cost of antihypertensive treatment was 13,771 CFA francs (21 euros). Non-adherence to antihypertensive medication were mostly noted in widows, patients without occupation, those with low education and no health insurance. At one year, blood pressure was controlled in 80% of the 42 patients still present. Non-control of blood pressure was related to poor therapeutic compliance (p<0.05).
CONCLUSION
This study highlights follow-up issues in hypertensive post-stroke patients with a high number of lost to follow-up. Blood pressure was controlled in patients who were regularly followed and adherent to antihypertensive treatment.
Topics: Humans; Hypertension; Female; Male; Middle Aged; Stroke; Cote d'Ivoire; Retrospective Studies; Antihypertensive Agents; Aged; Neurology; Hospital Departments; Medication Adherence; Follow-Up Studies
PubMed: 38846129
DOI: 10.48327/mtsi.v4i1.2024.366 -
Journal of the American Heart... Jun 2024The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal...
BACKGROUND
The mineralocorticoid receptor plays a significant role in the development of chronic kidney disease (CKD) and associated cardiovascular complications. Classic steroidal mineralocorticoid receptor antagonists are a therapeutic option, but their use in the clinic is limited due to the associated risk of hyperkalemia in patients with CKD. Finerenone is a nonsteroidal mineralocorticoid receptor antagonist that has been recently investigated in 2 large phase III clinical trials (FIDELIO-DKD [Finerenone in Reducing Kidney Failure and Disease Progression in Diabetic Kidney Disease] and FIGARO-DKD [Finerenone in Reducing Cardiovascular Mortality and Morbidity in Diabetic Kidney Disease]), showing reductions in kidney and cardiovascular outcomes.
METHODS AND RESULTS
We tested whether finerenone improves renal and cardiac function in a preclinical nondiabetic CKD model. Twelve weeks after 5/6 nephrectomy, the rats showed classic signs of CKD characterized by a reduced glomerular filtration rate and increased kidney weight, associated with left ventricular (LV) diastolic dysfunction and decreased LV perfusion. These changes were associated with increased cardiac fibrosis and reduced endothelial nitric oxide synthase activating phosphorylation (ser 1177). Treatment with finerenone prevented LV diastolic dysfunction and increased LV tissue perfusion associated with a reduction in cardiac fibrosis and increased endothelial nitric oxide synthase phosphorylation. Curative treatment with finerenone improves nondiabetic CKD-related LV diastolic function associated with a reduction in cardiac fibrosis and increased cardiac phosphorylated endothelial nitric oxide synthase independently from changes in kidney function. Short-term finerenone treatment decreased LV end-diastolic pressure volume relationship and increased phosphorylated endothelial nitric oxide synthase and nitric oxide synthase activity.
CONCLUSIONS
We showed that the nonsteroidal mineralocorticoid receptor antagonist finerenone reduces renal hypertrophy and albuminuria, attenuates cardiac diastolic dysfunction and cardiac fibrosis, and improves cardiac perfusion in a preclinical nondiabetic CKD model.
Topics: Animals; Mineralocorticoid Receptor Antagonists; Renal Insufficiency, Chronic; Naphthyridines; Ventricular Dysfunction, Left; Male; Disease Models, Animal; Fibrosis; Nitric Oxide Synthase Type III; Glomerular Filtration Rate; Ventricular Function, Left; Diastole; Kidney; Phosphorylation; Myocardium; Rats, Sprague-Dawley; Rats; Nephrectomy
PubMed: 38842271
DOI: 10.1161/JAHA.123.032971 -
Clinical Liver Disease 2024
Review
PubMed: 38841197
DOI: 10.1097/CLD.0000000000000090 -
Clinical profiling of patients admitted with acute heart failure: a comprehensive survival analysis.Frontiers in Cardiovascular Medicine 2024In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival...
BACKGROUND
In heart failure (HF), not all episodes of decompensation are alike. The study aimed to characterize the clinical groups of decompensation and perform a survival analysis.
METHODS
A retrospective study was conducted on patients consecutively admitted for HF from 2018 to 2023. Patients who died during admission were excluded (final number 1,668). Four clinical types of HF were defined: low cardiac output (:83), pulmonary congestion (:1,044), mixed congestion (:353), and systemic congestion (:188).
RESULTS
The low output group showed a higher prevalence of reduced left ventricular ejection fraction (93%) and increased biventricular diameters ( < 0.01). The systemic congestion group exhibited a greater presence of tricuspid regurgitation with dilatation and right ventricular dysfunction (:0.0001), worse renal function, and higher uric acid and CA125 levels (:0.0001). Diuretics were more commonly used in the mixed and, especially, systemic congestion groups (:0.0001). The probability of overall survival at 5 years was 49%, with higher survival in pulmonary congestion and lower in systemic congestion (:0.002). Differences were also found in survival at 1 month and 1 year (:0.0001).
CONCLUSIONS
Mortality in acute HF is high. Four phenotypic profiles of decompensation differ clinically, with distinct characteristics and varying prognosis in the short, medium, and long term.
PubMed: 38836065
DOI: 10.3389/fcvm.2024.1381514 -
Frontiers in Cardiovascular Medicine 2024Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B...
BACKGROUND
Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B (CVB) fulminant myocarditis successfully treated with veno-arterial extracorporeal membrane oxygenation (V-A ECMO).
CASE PRESENTATION
A previously healthy 7-day-old boy presented with fever for 4 days. Progressive cardiac dysfunction (weak heart sounds, hepatomegaly, pulmonary edema, ascites, and oliguria), decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS), transient ventricular fibrillation, dramatically elevated creatine kinase-MB (405.8 U/L), cardiac troponin I (25.85 ng/ml), and N-terminal pro-brain natriuretic peptide (NT-proBNP > 35,000 ng/L), and positive blood CVB ribonucleic acid indicated neonatal CVB fulminating myocarditis. It was refractory to mechanical ventilation, fluid resuscitation, inotropes, corticosteroids, intravenous immunoglobulin, and diuretics during the first 4 days of hospitalization (DOH 1-4). The deterioration was suppressed by V-A ECMO in the next 5 days (DOH 5-9), despite the occurrence of bilateral grade III intraventricular hemorrhage on DOH 7. Within the first 4 days after ECMO decannulation (DOH 10-13), he continued to improve with withdrawal of mechanical ventilation, LVEF > 60%, and FS > 30%. In the subsequent 4 days (DOH 14-17), his LVEF and FS decreased to 52% and 25%, and further dropped to 37%-38% and 17% over the next 2 days (DOH 18-19), respectively. There was no other deterioration except for cardiomegaly and paroxysmal tachypnea. Through strengthening fluid restriction and diuresis, and improving cardiopulmonary function, he restabilized. Finally, notwithstanding NT-proBNP elevation (>35,000 ng/L), cardiomegaly, and low LVEF (40%-44%) and FS (18%-21%) levels, he was discharged on DOH 26 with oral medications discontinued within 3 weeks postdischarge. In nearly three years of follow-up, he was uneventful, with interventricular septum hyperechogenic foci and mild mitral/tricuspid regurgitation.
CONCLUSIONS
Dynamic cardiac function monitoring via real-time echocardiography is useful for the diagnosis and treatment of NM/NEM. As a lifesaving therapy, ECMO may improve the survival rate of patients with NM/NEM. However, the "honeymoon period" after ECMO may cause the illusion of recovery. Regardless of whether the survivors of NM/NEM have undergone ECMO, close long-term follow-up is paramount to the prompt identification and intervention of abnormalities.
PubMed: 38836060
DOI: 10.3389/fcvm.2024.1364289 -
Federal Practitioner : For the Health... Feb 2024Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system...
BACKGROUND
Regardless of age, first-line therapy for uncomplicated hypertension includes thiazide diuretics, long-acting calcium channel blockers, and renin-angiotensin system inhibitors. Even though older adults are often at increased risk of adverse drug events, specific guidelines for choosing between different classes of antihypertensives are lacking. Given the prevalence of hypertension in older adults, clinicians should be aware of the increased risk of electrolyte disorders after the initiation of thiazide diuretics in this population.
CASE PRESENTATION
A patient aged > 90 years fell getting out of his bed 2 weeks following initiation of hydrochlorothiazide 25 mg daily medication therapy. Laboratory tests revealed a urine sodium of 35 mmol/L most consistent with hypovolemic hypoosmotic hyponatremia secondary to thiazide initiation. Hydrochlorothiazide was discontinued and sodium gradually normalized over the next 2 weeks without any other intervention.
CONCLUSIONS
Despite being recommended as first-line therapy for uncomplicated hypertension, thiazide diuretics may cause more harm than good in older adults with risk factors for thiazide-induced hyponatremia, which should be considered before initiation.
PubMed: 38835924
DOI: 10.12788/fp.0443