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An examination of the cardiac actions of PD117,302, a κ-opioid receptor agonist.

These studies examined the opioid and non-opioid in vivo and in vitro actions of PD117,302 (((±)-trans-N-methyl-N-[2-(l-pyrrolidinyl)-cyclohexyl]benzo[b]thiophene-4-acetamide), a kappa (κ)-opioid receptor agonist. PD117,302 selectively labeled the κ-opioid receptor in guinea pig cerebellar membranes and in mice the ED50 for analgesia was 2.3µmol/kg. A non opioid cardiovascular assessment of PD117,302 showed that it dose-dependently increased left-ventricular peak systolic pressure in rat isolated perfused hearts but reduced heart rate and blood pressure in anaesthetized rats. Over the concentr

Troponin I phosphorylation in spontaneously hypertensive rat heart: effect of beta-adrenergic stimulation.

We compared baseline and protein kinase A (PKA)-dependent troponin I (TnI) phosphorylation in 32Pi-labeled left ventricular myocytes from hearts of 26-wk spontaneously hypertensive rats (SHR) and Wistar-Kyoto controls (WKY). TnI phosphorylation was normalized to myosin light chain 2 phosphorylation, which was invariant. There was no difference in baseline TnI phosphorylation in SHR and WKY, but stimulation with isoproterenol, norepinephrine plus prazosin, forskolin, chloroadenosine 3',5'-cyclic monophosphate, or 3-isobutyl-1-methylxanthine caused a greater increase in TnI phosphorylation in th

Cardiac amyloidosis and aortic stenosis: a state-of-the-art review.

Cardiac amyloidosis is caused by the extracellular deposition of amyloid fibrils in the heart, involving not only the myocardium but also any cardiovascular structure. Indeed, this progressive infiltrative disease also involves the cardiac valves and, specifically, shows a high prevalence with aortic stenosis. Misfolded protein infiltration in the aortic valve leads to tissue damage resulting in the onset or worsening of valve stenosis. Transthyretin cardiac amyloidosis and aortic stenosis coexist in patients > 65 years in about 4-16% of cases, especially in those undergoing transcatheter aort

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… Myocardial contraction fraction by M-mode echocardiography is superior to ejection fraction in predicting mortality in transthyretin amyloidosis . … The myocardial contraction fraction is superior to ejection fraction in predicting survival in patients with AL cardiac amyloidosis . …

Roles of PKA, PI3K, and cPLA2 in the NO-mediated negative inotropic effect of beta2-adrenoceptor agonists in guinea pig right papillary muscles.

Although beta(2)-adrenoceptors represent 15-25% of beta-adrenoceptors in the guinea pig heart, their functionality is controversial. We assessed the inotropic effects of beta(2)-adrenoceptor partial agonists in right papillary muscles. Salbutamol induced a small but significant concentration-dependent negative inotropic effect (NIE, -5% at 60 nM) followed by a moderate positive inotropic effect (+36% at 6 microM) due to activation of beta(1)-adrenoceptors. In the presence of 4 microM atenolol, the concentration-dependent NIE (-12% at 6 microM) was biphasic, best described by a double logistic

Loss of PI3Kγ enhances cAMP-dependent MMP remodeling of the myocardial N-cadherin adhesion complexes and extracellular matrix in response to early biomechanical stress.

RATIONALE: Mechanotransduction and the response to biomechanical stress is a fundamental response in heart disease. Loss of phosphoinositide 3-kinase (PI3K)γ, the isoform linked to G protein-coupled receptor signaling, results in increased myocardial contractility, but the response to pressure overload is controversial. OBJECTIVE: To characterize molecular and cellular responses of the PI3Kγ knockout (KO) mice to biomechanical stress. METHODS AND RESULTS: In response to pressure overload, PI3KγKO mice deteriorated at an accelerated rate compared with wild-type mice despite increased basal my

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Cardiac amyloidosis responding to bortezomib: case report and review of literature.

We report a case of a 53-year old patient with symptoms of congestive heart failure in whom a restrictive cardiomyopathy and a kappa-chain monoclonal gammopahty were diagnosed. Treatment with eight cycles of Bortezomib, a proteasome inhibitor, resulted in a significant regression of myocardial amyloid deposition and a notable clinical and hemodynamic improvement. Over the last few years, the management of cardiac amyloidosis has taken advantage of many of the advances of the chemotherapeutic regimens, as well as the wider availability of stem cell transplantation. The management of cardiac amy

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… This is mainly due to the direct effect of amyloid deposition on myocardial contraction and relaxation; a light chain-induced oxidant stress may be also involved as well [ 5 ]. …

An integrative review of nonobvious puzzles of cellular and molecular cardiooncology.

Oncologic patients are subjected to four major treatment types: surgery, radiotherapy, chemotherapy, and immunotherapy. All nonsurgical forms of cancer management are known to potentially violate the structural and functional integrity of the cardiovascular system. The prevalence and severity of cardiotoxicity and vascular abnormalities led to the emergence of a clinical subdiscipline, called cardiooncology. This relatively new, but rapidly expanding area of knowledge, primarily focuses on clinical observations linking the adverse effects of cancer therapy with deteriorated quality of life of

From Clinical Clues to Final Diagnosis: The Return of Detective Work to Clinical Medicine in Cardiac Amyloidosis.

Cardiac amyloidosis is frequently misdiagnosed, denying patients the opportunity for timely and appropriate management of the disease. The purpose of this review and case studies is to raise awareness of the diagnostic "red flags" associated with cardiac amyloidosis and the currently available non-invasive strategies for diagnosis. The review focuses on the identification of one of the two main types of cardiac amyloidosis, transthyretin amyloid cardiomyopathy, and non-invasive tools to distinguish this from light-chain amyloidosis. A diagnostic algorithm centered around the use of non-invasiv

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… . # Echocardiographic, speckle-strain and tissue doppler “red flags”: Heart failure normal or mid-range ejection fraction; increased wall thickness; left atrial enlargement; low stroke volume index; low-flow, low-gradient aortic stenosis (Stage D2); low myocardial contraction fraction; advanced diastolic … contraction fraction; advanced diastolic dysfunction; impaired global longitudinal strain with apical sparing; low mitral annular tissue Doppler S' (average septal and lateral annulus) ( 24 ) . …

Cardiomyopathy: pathogenesis and therapeutic interventions.

Cardiomyopathy is a group of disease characterized by structural and functional damage to the myocardium. The etiologies of cardiomyopathies are diverse, spanning from genetic mutations impacting fundamental myocardial functions to systemic disorders that result in widespread cardiac damage. Many specific gene mutations cause primary cardiomyopathy. Environmental factors and metabolic disorders may also lead to the occurrence of cardiomyopathy. This review provides an in-depth analysis of the current understanding of the pathogenesis of various cardiomyopathies, highlighting the molecular and

Exploring Resting Sinus Tachycardia in Cancer Care: A Comprehensive Review.

Resting sinus tachycardia is frequently encountered in cancer patients. It affects a wide variety of cancer patients and is associated with distressing symptoms. Cancer-associated resting sinus tachycardia varies in its underlying mechanism. It can stem from the tumor burden or the side effects of chemotherapy/radiotherapy, or it can be secondary to paraneoplastic syndrome or the sequalae of cancer itself (infection, anemia, thrombosis, etc.). The clinical significance of resting sinus tachycardia extends beyond mere symptomatology, as it can potentially indicate severe complications which may

Mechanisms and effects of metformin on skeletal muscle disorders.

Skeletal muscle disorders are mostly genetic and include several rare diseases. With disease progression, muscle fibrosis and adiposis occur, resulting in limited mobility. The long course of these diseases combined with limited treatment options affect patients both psychologically and economically, hence the development of novel treatments for neuromuscular diseases is crucial to obtain a better quality of life. As a widely used hypoglycemic drug in clinical practice, metformin not only has anti-inflammatory, autophagy-regulating, and mitochondrial biogenesis-regulating effects, but it has a

Значительное сокращение числа пациентов с несколькими миломами с левой венерической венерической глобальной продольной траекторией: экспериментальный анализ случайной осведомленности.

Множественная миелома (ММ) - это злонамеренный вид, связанный с сердечно-сосудистыми осложнениями. Хотя эхокардиография играет ключевую роль в оценке сердечной функции, ее использование для последующей работы с пациентами, страдающими от болезней, носит ограниченный характер. Для этого описательного анализа мы приводим несколько рекомендуемых объективных показателей систолической функции левого желудочка (LV), пиковой глобальной продольной деформации (PGLS) и систолической функции правого желудочка (RV) 147 Пациенты MM на различных этапах лечения были направлены в нашу эхокардиографическую лаб

Recurrent Syncope, a Clue in Amyloid Cardiomyopathy.

Infiltrative cardiomyopathies include a variety of disorders that lead to myocardial thickening resulting in a constellation of clinical manifestations and eventually heart failure that could be the first clue to reach the diagnosis. Among the more described infiltrative diseases of the heart is amyloid cardiomyopathy. The disease usually presents with subtle, nonspecific symptoms. Herein, we illustrate a case of recurrent syncope as the initial presenting symptom for systemic amyloid with polyneuropathy and cardiomyopathy as a cause of syncope. The article illustrates the role of advanced car

Spatiotemporal dynamics of beta-adrenergic cAMP signals and L-type Ca2+ channel regulation in adult rat ventricular myocytes: role of phosphodiesterases.

Steady-state activation of cardiac beta-adrenergic receptors leads to an intracellular compartmentation of cAMP resulting from localized cyclic nucleotide phosphodiesterase (PDE) activity. To evaluate the time course of the cAMP changes in the different compartments, brief (15 seconds) pulses of isoprenaline (100 nmol/L) were applied to adult rat ventricular myocytes (ARVMs) while monitoring cAMP changes beneath the membrane using engineered cyclic nucleotide-gated channels and within the cytosol with the fluorescence resonance energy transfer-based sensor, Epac2-camps. cAMP kinetics in the tw

Interdisciplinary Multidimensional Assessment of Transthyretin Amyloidosis before and after Tafamidis.

BackgroundClinically, there is considerable heterogeneity in the presentation of transthyretin amyloidosis (ATTR), which ranges from primarily cardiac and primarily neurologic to mixed disease, among other manifestations. Because of this complex presentation, the diagnosis and management of patients with ATTR are often challenging and should be performed in interdisciplinary centers specialized in amyloidosis. Here, we aimed to increase awareness of ATTR detection and pathophysiology through a multidimensional multiorgan approach.Case reportWe reported on a 60-year-old man with wild-type ATTR

Cardiac amyloidosis: From diagnosis to therapeutics breakthroughs.

Cardiac amyloidosis (CA) is a progressive infiltrative cardiomyopathy resulting from the deposition of misfolded amyloid fibrils in the myocardium and heart valves, with the main forms being amyloid light-chain (AL), transthyretin-related (ATTR) (wild-type or hereditary), and amyloid A amyloidosis. Although historically underdiagnosed, recent advances in non-invasive imaging techniques such as cardiac magnetic resonance imaging and bone scintigraphy have significantly improved its recognition. This review outlines the current diagnostic approaches and therapeutic advancements in CA, emphasizin

Всеобъемлющая эхокардиография левого атриума и левого вентрила, использующая современные методы, помогает лучше разоблачать испытательный фибрилляция у пациентов с гипертрофической кардиомиопатией

Предварительная фибрилляция (AF) — важная аритмия в гипертрофической кардиомиопатии (HCM). Мы стремились выяснить, повышает ли сложная оценка левого желудочка (LV) с использованием современных методов эхокардиографии, помимо левого предсердия (LA), вероятность диагностирования АФ. Стандартная эхокардиография, 2D и 3D спекл, была проведена для оценки LA и LV у пациентов HCM и здоровых добровольцев. Из 128 Первоначально квалифицированные пациенты из HCM, 60 К числу выполненных критериев относятся критерии, из которых 43 У него была история AF, и 17 были без AF. Индекс объема LA и пиковый штамм,

Resistant Ventricular Arrhythmia and the Role of Overdrive Pacing in the Suppression of the Electrical Storm.

Ventricular arrhythmia storm is a state of cardiac instability characterized by multiple ventricular arrhythmias or multiple ICD therapies within a 24-hour duration. Management of this life-threatening state depends on the reversal of the cause besides either electrical or medical management of the arrhythmia. We report a case of a 54-year-old male who underwent a percutaneous coronary intervention following massive acute myocardial infarction. Afterwards, he developed frequent life-threatening ventricular arrhythmias that required multiple shocks and antiarrhythmic medications. Despite all th