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Bulletin of Experimental Biology and... Jun 2024A number of pharmacological drugs have side effects that contribute to the occurrence of atrial fibrillation, the most common type of cardiac rhythm disorders. The...
Suprastin (Chloropyramine) Causes Proarrhythmic Deterioration of Excitation Conduction, Depolarization and Potentiates Adrenergic Automaticity in the Pulmonary Veins Myocardium.
A number of pharmacological drugs have side effects that contribute to the occurrence of atrial fibrillation, the most common type of cardiac rhythm disorders. The clinical use of antihistamines is widespread; however, information regarding their anti- and/or proarrhythmic effects is contradictory. In this work, we studied the effects and mechanisms of the potential proarrhythmic action of the first-generation antihistamine chloropyramine (Suprastin) in the atrial myocardium and pulmonary vein (PV) myocardial tissue. In PV, chloropyramine caused depolarization of the resting potential and led to reduction of excitation wave conduction. These effects are likely due to suppression of the inward rectifier potassium current (IK1). In presence of epinephrine, chloropyramine induced spontaneous automaticity in the PV and could not be suppressed by atrial pacing. Chloropyramine change functional characteristics of PV and contribute to occurrence of atrial fibrillation. It should be noted that chloropyramine does not provoke atrial tachyarrhythmias, but create conditions for their occurrence during physical exercise and sympathetic stimulation.
PubMed: 38896318
DOI: 10.1007/s10517-024-06104-0 -
International Journal of Molecular... May 2024Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement... (Review)
Review
Cirrhotic cardiomyopathy (CCM) is defined as cardiac dysfunction associated with cirrhosis in the absence of pre-existing heart disease. CCM manifests as the enlargement of cardiac chambers, attenuated systolic and diastolic contractile responses to stress stimuli, and repolarization changes. CCM significantly contributes to mortality and morbidity in patients who undergo liver transplantation and contributes to the pathogenesis of hepatorenal syndrome/acute kidney injury. There is currently no specific treatment. The traditional management for non-cirrhotic cardiomyopathies, such as vasodilators or diuretics, is not applicable because an important feature of cirrhosis is decreased systemic vascular resistance; therefore, vasodilators further worsen the peripheral vasodilatation and hypotension. Long-term diuretic use may cause electrolyte imbalances and potentially renal injury. The heart of the cirrhotic patient is insensitive to cardiac glycosides. Therefore, these types of medications are not useful in patients with CCM. Exploring the therapeutic strategies of CCM is of the utmost importance. The present review summarizes the possible treatment of CCM. We detail the current status of non-selective beta-blockers (NSBBs) in the management of cirrhotic patients and discuss the controversies surrounding NSBBs in clinical practice. Other possible therapeutic agents include drugs with antioxidant, anti-inflammatory, and anti-apoptotic functions; such effects may have potential clinical application. These drugs currently are mainly based on animal studies and include statins, taurine, spermidine, galectin inhibitors, albumin, and direct antioxidants. We conclude with speculations on the future research directions in CCM treatment.
Topics: Humans; Liver Cirrhosis; Cardiomyopathies; Animals; Adrenergic beta-Antagonists; Antioxidants
PubMed: 38892040
DOI: 10.3390/ijms25115849 -
Scientific Reports Jun 2024Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and...
Binge drinking (BD) contributes strongly to the harms of alcohol use disorder. Most rodent models do not result in binge-level blood alcohol concentrations (BACs), and to better understand individual and sex differences in neurobiological mechanisms related to BD, the use of outbred rat strains would be valuable. Here, we developed a novel BD model where after 3+ months of intermittent access to 20% alcohol Wistar rats drank, twice a week, with two 5-min intake (what we called Two-shot) separated by a 10-min break. Our findings showed during Two-Shot that most animals reached ≥ 80 mg% BAC levels (when briefly food-restricted). However, when increasing alcohol concentrations from 20 to 30%, 40%, or 50%, rats titrated to similar intake levels, suggesting rapid sensing of alcohol effects even when front-loading. Two-Shot drinking was reduced in both sexes by naltrexone (1 mg/kg), validating intake suppression by a clinical therapeutic agent for human problem drinking. Further, both propranolol (β-adrenergic receptor antagonist) and prazosin (α1-adrenergic receptor antagonist) reduced female but not male BD at the lower dose. Thus, our results provide a novel model for BD in outbred rats and suggest that female binging is more sensitive to adrenergic modulation than males, perhaps providing a novel sex-related therapy.
Topics: Animals; Female; Binge Drinking; Male; Rats; Disease Models, Animal; Rats, Wistar; Ethanol; Adrenergic Antagonists; Naltrexone; Propranolol; Sex Factors; Alcohol Drinking
PubMed: 38890353
DOI: 10.1038/s41598-024-64565-9 -
Analytical Chemistry Jul 2024Hepatic toxicity is a leading cause of the termination of clinical trials and the withdrawal of therapeutics following regulatory approval. The detection of drug-induced...
Hepatic toxicity is a leading cause of the termination of clinical trials and the withdrawal of therapeutics following regulatory approval. The detection of drug-induced liver injury (DILI) is therefore of importance to ensure patient safety and the effectiveness of novel small molecules and drugs. DILI encompasses drug-induced steatosis (DIS) and drug-induced phospholipidosis (DIPL) which involve the accumulation of excess intracellular lipids. Here, we develop hyperspectral stimulated Raman scattering (SRS) microscopy as a label-free methodology for discriminating DIS and DIPL in mammalian cell culture. We demonstrate that hyperspectral SRS imaging in tandem with spectral phasor analysis is capable of discriminating DIS and DIPL based on the nature and distribution of intracellular lipids resulting from each process. To demonstrate the practical application of this methodology, we develop a panel of alkyne-tagged propranolol analogues that display varying DILI effects. Using hyperspectral SRS imaging together with spectral phasor analysis, our label-free methodology corroborated the standard fluorescence-based assay for DILI. As a label-free screening method, it offers a convenient and expedient methodology for visualizing hepatotoxicity in cell cultures which could be integrated into the early stages of the drug development process for screening new chemical entities for DILI.
Topics: Chemical and Drug Induced Liver Injury; Humans; Nonlinear Optical Microscopy; Spectrum Analysis, Raman; Propranolol; Hep G2 Cells
PubMed: 38889191
DOI: 10.1021/acs.analchem.4c01285 -
Annals of Noninvasive Electrocardiology... Jul 2024This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and...
OBJECTIVES
This study aimed to retrospectively assess cardiac autonomic activity in children with LQTS, considering genotype, symptoms, sex, age, and beta-blocker therapy (BB) and compare it to healthy controls.
METHODS
Heart rate variability (HRV), using power spectrum analysis, was analyzed in 575 Holter recordings from 116 children with LQTS and in 69 healthy children. The data were categorized into four age-groups and four heart rate (HR) ranges.
RESULTS
In LQT1 and LQT2, increasing HR corresponded to significantly lower low (LF) and high frequency (HF) compared to controls. Total power (PTOT) was lower in all LQT1 age-groups compared to controls at HR 120-140 bpm (1-15 years: p < .01; 15-18 years: p = .03). At HR 80-100, LQT1 patients aged 1-10 years had lower HF than LQT2 patients (1-5 years: p = .05; 5-10 years: p = .02), and LQT2 patients aged 15-18 years had lower HF than LQT1 patients (p < .01). Symptomatic patients aged 10-15 years had lower PTOT at HR 100-120 bpm than asymptomatic patients (p = .04). LQT1 girls aged 10-15 and 15-18 years had a lower PTOT (10-15 years: p = .04; 15-18 years: p = .02) than boys.
CONCLUSION
This study shows a correlation between HR and changes in HRV parameters. At higher HRs, LQTS patients generally had lower HRV values than controls, suggesting an abnormal autonomic response. These results may strengthen the link between physical activity and arrhythmias in LQTS.
Topics: Humans; Adolescent; Female; Child; Male; Heart Rate; Electrocardiography, Ambulatory; Long QT Syndrome; Retrospective Studies; Child, Preschool; Infant; Case-Control Studies; Adrenergic beta-Antagonists
PubMed: 38888254
DOI: 10.1111/anec.13132 -
Vascular Health and Risk Management 2024Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the... (Review)
Review
Kaposiform hemangioendothelioma(KHE) without Kasabach-Merritt phenomenon is a rare tumor primarily observed in pediatric patients; however, its documentation in the literature remains limited. We reported about a 1-year-old boy diagnosed with superficial KHE who received oral propranolol in combination with topical sirolimus and reviewed relevant reports and treatment of superficial KHE.
Topics: Humans; Infant; Male; Administration, Oral; Biopsy; Hemangioendothelioma; Propranolol; Sarcoma, Kaposi; Sirolimus; Treatment Outcome
PubMed: 38883398
DOI: 10.2147/VHRM.S461505 -
The Journal of the Association of... May 2024Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All...
Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective β1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.
Topics: Humans; Renal Insufficiency, Chronic; Sodium-Glucose Transporter 2 Inhibitors; India; Bisoprolol; Angiotensin Receptor Antagonists; Consensus; Adrenergic beta-1 Receptor Antagonists
PubMed: 38881115
DOI: 10.59556/japi.72.0543 -
The Journal of the Association of... Apr 2024The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic... (Observational Study)
Observational Study
Effect of α-blockers on Handgrip Test Response of Diastolic Blood Pressure in Hypertensive, Benign Hypertrophy of Prostate Patients in a Therapeutics Clinic, Kolkata: A Cross-sectional Study.
BACKGROUND
The isometric handgrip (IHG) test is commonly used to detect sympathetic autonomic dysfunction. Tamsulosin, approved for the management of symptomatic benign prostatic hyperplasia (BPH), acts as an antagonist for α1-adrenergic receptors (α1-AR), whereas prazosin, an α receptor blocker, being less selective than tamsulosin, is used as an antihypertensive agent clinically. Our objective was to investigate if there is a distinction in blood pressure (BP) increase during IHG exercise between individuals with essential hypertension taking tamsulosin compared to those taking prazosin.
MATERIALS AND METHODS
A cross-sectional observational study was performed on 50 subjects receiving tablet prazosin and 47 subjects receiving tamsulosin, who were asked to undergo an IHG test. Pre- and posttest BP was recorded for both the groups, and the difference in diastolic BP (DBP) (delta DBP) was compared between the groups and to their respective baseline values.
RESULTS
Post-IHG test, mean DBP was found to be 93.98 ± 9.13 mm Hg in the prazosin group and 101.00 ± 12.05 mm Hg in the tamsulosin group, respectively. The change of delta DBP in the tamsulosin group was significant, but the prazosin group showed an insignificant rise in DBP.
CONCLUSION
Prazosin, being less selective than tamsulosin in terms of α1 receptor antagonism, showed suppression of BP during IHG. Tamsulosin demonstrates high selectivity for prostatic receptors while showing minimal affinity for vascular receptors. As a result, its impact on BP is expected to be minimal.
Topics: Humans; Male; Cross-Sectional Studies; Prostatic Hyperplasia; Prazosin; Tamsulosin; Middle Aged; Adrenergic alpha-1 Receptor Antagonists; Blood Pressure; Hypertension; Hand Strength; Aged; Antihypertensive Agents; India
PubMed: 38881078
DOI: 10.59556/japi.72.0501 -
The American Journal of the Medical... Jun 2024Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines... (Review)
Review
Incomplete decongestion is the main cause of readmission in the early post-discharge period of a hospitalization for acute heart failure. Recent heart failure guidelines have highlighted initiation and rapid up-titration of quadruple therapy with angiotensin receptor neprilysin inhibitor, beta adrenergic receptor blocker, mineralocorticoid receptor antagonist, and sodium glucose cotransporter 2 inhibitor to prevent hospitalizations for heart failure with reduced ejection fraction. However, full decongestion remains the foremost therapeutic goal of hospitalization for heart failure. While early addition of sodium glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists may be helpful, the value of the other therapeutics comes after decongestion is complete.
PubMed: 38880301
DOI: 10.1016/j.amjms.2024.06.002 -
Parkinsonism & Related Disorders Jun 2024We review the epidemiologic literature on potential protective and risk factors in Parkinson's Disease (PD). Prior research identified numerous possible protective and... (Review)
Review
We review the epidemiologic literature on potential protective and risk factors in Parkinson's Disease (PD). Prior research identified numerous possible protective and risk factors. Potential protective factors include tobacco abuse, physical activity, urate levels, NSAID use, calcium channel blocker use, statin use, and use of some α1-adrenergic antagonists. Some potential protective factors could be products of reverse causation, including increased serum urate, tobacco abuse, and coffee-tea-caffeine consumption. Potential risk factors include traumatic brain injury, pesticide exposure, organic solvent exposure, lead exposure, air pollution, Type 2 Diabetes, some dairy products, cardiovascular disease, and some infections including Hepatitis C, H. pylori, and COVID-19. Potential non-environmental risk factors include bipolar disorder, essential tremor, bullous pemphigoid, and inflammatory bowel disease. There is an inverse relationship with PD and risk of most cancers. Though many potential protective and risk factors for PD were identified, research has not yet led to unique, rigorous prevention trials or successful disease-modifying interventions. While efforts to reduce exposure to some industrial toxicants are well justified, PD incidence might be most effectively reduced by mitigation of risks, such as Type 2 Diabetes, air pollution, traumatic brain injury, or physical inactivity, that are general public health intervention targets.
PubMed: 38879999
DOI: 10.1016/j.parkreldis.2024.107026