Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.

• MeSH
• chronická nemoc MeSH
• fibróza MeSH
• guanosinmonofosfát cyklický metabolismus   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• morfoliny MeSH
• oxidační stres * účinky léků   MeSH
• potkani Sprague-Dawley * MeSH
• potkani transgenní MeSH
• pyridiny farmakologie   terapeutické užití   MeSH
• pyrimidiny MeSH
• remodelace komor účinky léků   MeSH
• rozpustná guanylátcyklasa * metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• srdeční selhání * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

This state-of-the-art review aimed to synthesize evidence from various sex-stratified studies on aortic stenosis (AS), focusing on the difference in clinical presentation, anatomical characteristics, pathophysiology, and management of AS. In comparison to men, women with AS are present at later stages, are older, more symptomatic, frailer, and exhibit higher operative risk [Society of Thoracic Surgeons (STS) score]. Women tend to have smaller aortic valve (AV) areas and left ventricular (LV) outflow tract, leading to lower stroke volumes (SVs) than men and have a higher prevalence of paradoxical, low-flow, low-gradient AS. In women, chronic pressure overload due to AS results in concentric LV remodelling and hypertrophy, characterized by reduced LV cavities, higher filling pressures, lower wall stress, and more diastolic dysfunction. Conversely, men exhibit more dilated eccentric LV remodelling and hypertrophy. AVs in women are less calcified but more fibrotic. Moreover, women are often underdiagnosed, have severity underestimated, and experience delays or receive fewer referrals for AV replacement (AVR). However, women tend to benefit from transcatheter AVR (TAVR) with a long-term survival advantage over men, although the incidence of vascular complications and bleeding events in 30 days after TAVR is higher in women. Surgical AVR (SAVR) in women has high operative risk, is technically demanding and has poorer outcomes with increased mortality at 30 days compared to men. According to the STS score and EuroSCORE, the female sex itself is considered a risk factor for SAVR. Therefore, addressing sex-related disparities in AS and increasing awareness among physicians promises improved diagnosis and treatment, facilitating equitable care and the development of sex-specific personalized medicine.

• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Chae, S, McDowell, KW, Baur, ML, Long, SA, Tufano, JJ, and Stone, MH. Accentuated eccentric loading and alternative set structures: A narrative review for potential synergies in resistance training. J Strength Cond Res 38(11): 1987-2000, 2024-As athletes become adapted to training over time, it becomes more difficult to develop their strength and power. In a conventional resistance training strategy, volume or load may be increased to provide novel stimuli to break through a plateau. However, physiological stress markers increase with increased volume or load, which is an innate shortcoming. In that case, practitioners strive to develop unconventional strategies that could increase training stimuli while adjusting fatigue. Two programming tactics, accentuated eccentric loading (AEL) using eccentric overload and alternative set structures (AS) using intraset rests, have been reported to increase training stimuli and alleviate fatigue, respectively. Importantly, when merging AEL and AS in various contexts, the 2 benefits could be accomplished together. Because AEL and AS cause different outcomes, it is important to deal with when and how they may be integrated into periodization. Moreover, prescribing eccentric overload and intraset rests requires logistical considerations that need to be addressed. This review discusses the scientific and practical aspects of AEL and AS to further optimize strength and power adaptations. This review discusses (a) scientific evidence as to which tactic is effective for a certain block, (b) potential practical applications, and (c) related discussions and future research directions.

• MeSH
• kosterní svaly fyziologie   MeSH
• lidé MeSH
• odporový trénink * metody   MeSH
• sportovci MeSH
• sportovní výkon fyziologie   MeSH
• svalová síla * fyziologie   MeSH
• svalová únava fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: Heart failure (HF) is a frequent cause of morbidity and mortality of end-stage kidney disease (ESKD) patients on hemodialysis. It is not easy to distinguish HF from water overload. The traditional HF definition has low sensitivity and specificity in this population. Moreover, many patients on hemodialysis have exercise limitations unrelated to HF. Therefore, we postulated two new HF definitions ((1) Modified definition of the Acute Dialysis Quality Improvement working group; (2) Hemodynamic definition based on the calculation of the effective cardiac output). We hypothesize that the newer definitions will better identify patients with higher number of endpoints and with more advanced structural heart disease. METHODS: Cohort, observational, longitudinal study with recording predefined endpoints. Patients (n = 300) treated by hemodialysis in six collaborating centers will be examined centrally in a tertiary cardiovascular center every 6-12 months lifelong or till kidney transplantation by detailed expert echocardiography with the calculation of cardiac output, arteriovenous dialysis fistula flow volume calculation, bio-impedance, and basic laboratory analysis including NTproBNP. Effective cardiac output will be measured as the difference between measured total cardiac output and arteriovenous fistula flow volume and systemic vascular resistance will be also assessed non-invasively. In case of water overload during examination, dry weight adjustment will be recommended, and the patient invited for another examination within 6 weeks. A composite major endpoint will consist of (1) Cardiovascular death; (2) HF worsening/new diagnosis of; (3) Non-fatal myocardial infarction or stroke. The two newer HF definitions will be compared with the traditional one in terms of time to major endpoint analysis. DISCUSSION: This trial will differ from others by: (1) detailed repeated hemodynamic assessment including arteriovenous access flow and (2) by careful assessment of adequate hydration to avoid confusion between HF and water overload.

• MeSH
• chronická renální insuficience * komplikace   MeSH
• chronické selhání ledvin * diagnóza   terapie   komplikace   MeSH
• dialýza ledvin škodlivé účinky   MeSH
• lidé MeSH
• longitudinální studie MeSH
• pozorovací studie jako téma MeSH
• srdeční selhání * diagnóza   etiologie   terapie   MeSH
• voda MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• protokol klinické studie MeSH
• Geografické názvy
• Česká republika MeSH

Sodium is the main osmotically active ion in the extracellular fluid and its concentration goes hand in hand with fluid volume. Under physiological conditions, homeostasis of sodium and thus amount of fluid is regulated by neural and humoral interconnection of body tissues and organs. Both heart and kidneys are crucial in maintaining volume status. Proper kidney function is necessary to excrete regulated amount of water and solutes and adequate heart function is inevitable to sustain renal perfusion pressure, oxygen supply etc. As these organs are bidirectionally interconnected, injury of one leads to dysfunction of another. This condition is known as cardiorenal syndrome. It is divided into five subtypes regarding timeframe and pathophysiology of the onset. Hemodynamic effects include congestion, decreased cardiac output, but also production of natriuretic peptides. Renal congestion and hypoperfusion leads to kidney injury and maladaptive activation of renin-angiotensin-aldosterone system and sympathetic nervous system. In cardiorenal syndromes sodium and water excretion is impaired leading to volume overload and far-reaching negative consequences, including higher morbidity and mortality of these patients. Keywords: Cardiorenal syndrome, Renocardiac syndrome, Volume overload, Sodium retention.

• MeSH
• homeostáza * fyziologie   MeSH
• kardiorenální syndrom * metabolismus   patofyziologie   MeSH
• ledviny metabolismus   patofyziologie   MeSH
• lidé MeSH
• sodík * metabolismus   MeSH
• voda metabolismus   MeSH
• vodní a elektrolytová nerovnováha metabolismus   patofyziologie   MeSH
• vodní a elektrolytová rovnováha * fyziologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

While phosphodiesterase-5 inhibition (PED5i) may prevent hypertrophy and failure in pressure-overloaded heart in an experimental model, the impact of PDE5i on volume-overload (VO)-induced hypertrophy is unknown. It is also unclear whether the hypertrophied right ventricle (RV) and left ventricle (LV) differ in their responsiveness to long-term PDE5i and if this therapy affects renal function. The goal of this study was to elucidate the effect of PDE5i treatment in VO due to aorto-caval fistula (ACF) and to compare PDE5i treatment with standard heart failure (HF) therapy with angiotensin-converting enzyme inhibitor (ACEi). ACF/sham procedure was performed on male HanSD rats aged 8 weeks. ACF animals were randomized for PDE5i sildenafil, ACEi trandolapril, or placebo treatments. After 20 weeks, RV and LV function (echocardiography, pressure-volume analysis), myocardial gene expression, and renal function were studied. Separate rat cohorts served for survival analysis. ACF led to biventricular eccentric hypertrophy (LV: +68%, RV: +145%), increased stroke work (LV: 3.6-fold, RV: 6.7-fold), and reduced load-independent systolic function (PRSW, LV: -54%, RV: -51%). Both ACF ventricles exhibited upregulation of the genes of myocardial stress and glucose metabolism. ACEi but not PDE5i attenuated pulmonary congestion, LV remodeling, albuminuria, and improved survival (median survival in ACF/ACEi was 41 weeks vs. 35 weeks in ACF/placebo, p = .02). PDE5i increased cyclic guanosine monophosphate levels in the lungs, but not in the RV, LV, or kidney. PDE5i did not improve survival rate and cardiac and renal function in ACF rats, in contrast to ACEi. VO-induced HF is not responsive to PDE5i therapy.

• MeSH
• inhibitory ACE * farmakologie   MeSH
• inhibitory fosfodiesterasy 5 * farmakologie   MeSH
• kardiomegalie farmakoterapie   MeSH
• krysa rodu rattus MeSH
• remodelace komor * MeSH
• srdeční selhání * farmakoterapie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Valvular heart disease leads to ventricular pressure and/or volume overload. Pressure overload leads to fibrosis, which might regress with its resolution, but the limits and details of this reverse remodeling are not known. To gain more insight into the extent and nature of cardiac fibrosis in valve disease, we analyzed needle biopsies taken from the interventricular septum of patients undergoing surgery for valve replacement focusing on the expression and distribution of major extracellular matrix protein involved in this process. Proteomic analysis performed using mass spectrometry revealed an excellent correlation between the expression of collagen type I and III, but there was little correlation with the immunohistochemical staining performed on sister sections, which included antibodies against collagen I, III, fibronectin, sarcomeric actin, and histochemistry for wheat germ agglutinin. Surprisingly, the immunofluorescence intensity did not correlate significantly with the gold standard for fibrosis quantification, which was performed using Picrosirius Red (PSR) staining, unless multiplexed on the same tissue section. There was also little correlation between the immunohistochemical markers and pressure gradient severity. It appears that at least in humans, the immunohistochemical pattern of fibrosis is not clearly correlated with standard Picrosirius Red staining on sister sections or quantitative proteomic data, possibly due to tissue heterogeneity at microscale, comorbidities, or other patient-specific factors. For precise correlation of different types of staining, multiplexing on the same section is the best approach.

• MeSH
• aortální insuficience metabolismus   patologie   chirurgie   MeSH
• aortální stenóza * metabolismus   patologie   chirurgie   MeSH
• extracelulární matrix - proteiny * metabolismus   analýza   MeSH
• fibróza * metabolismus   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mezikomorová přepážka patologie   metabolismus   MeSH
• senioři MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

The aim was to evaluate the effects of renal denervation (RDN) on autoregulation of renal hemodynamics and the pressure-natriuresis relationship in Ren-2 transgenic rats (TGR) with aorto-caval fistula (ACF)-induced heart failure (HF). RDN was performed one week after creation of ACF or sham-operation. Animals were prepared for evaluation of autoregulatory capacity of renal blood flow (RBF) and glomerular filtration rate (GFR), and of the pressure-natriuresis characteristics after stepwise changes in renal arterial pressure (RAP) induced by aortic clamping. Their basal values of blood pressure and renal function were significantly lower than with innervated sham-operated TGR (p < 0.05 in all cases): mean arterial pressure (MAP) (115 ± 2 vs. 160 ± 3 mmHg), RBF (6.91 ± 0.33 vs. 10.87 ± 0.38 ml.min-1.g-1), urine flow (UF) (11.3 ± 1.79 vs. 43.17 ± 3.24 μl.min-1.g-1) and absolute sodium excretion (UNaV) (1.08 ± 0.27 vs, 6.38 ± 0.76 μmol.min-1.g-1). After denervation ACF TGR showed improved autoregulation of RBF: at lowest RAP level (80 mmHg) the value was higher than in innervated ACF TGR (6.92 ± 0.26 vs. 4.54 ± 0.22 ml.min-1.g-1, p < 0.05). Also, the pressure-natriuresis relationship was markedly improved after RDN: at the RAP of 80 mmHg UF equaled 4.31 ± 0.99 vs. 0.26 ± 0.09 μl.min-1.g-1 recorded in innervated ACF TGR, UNaV was 0.31 ± 0.05 vs. 0.04 ± 0.01 μmol min-1.g-1 (p < 0.05 in all cases). In conclusion, in our model of hypertensive rat with ACF-induced HF, RDN improved autoregulatory capacity of RBF and the pressure-natriuresis relationship when measured at the stage of HF decompensation.

• MeSH
• hodnoty glomerulární filtrace MeSH
• hypertenze * MeSH
• kardiorenální syndrom * MeSH
• krevní tlak MeSH
• krysa rodu rattus MeSH
• ledviny MeSH
• natriuréza MeSH
• píštěle * MeSH
• potkani transgenní MeSH
• renální oběh MeSH
• srdeční selhání * MeSH
• sympatektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Renal nerves play a critical role in cardiorenal interactions. Renal denervation (RDN) improved survival in some experimental heart failure (HF) models. It is not known whether these favorable effects are indirect, explainable by a decrease in vascular afterload, or diminished neurohumoral response in the kidneys, or whether RDN procedure per se has direct myocardial effects in the failing heart. To elucidate mechanisms how RDN affects failing heart, we studied load-independent indexes of ventricular function, gene markers of myocardial remodeling, and cardiac sympathetic signaling in HF, induced by chronic volume overload (aorto-caval fistula, ACF) of Ren2 transgenic rats. Volume overload by ACF led to left ventricular (LV) hypertrophy and dysfunction, myocardial remodeling (upregulated Nppa, MYH 7/6 genes), increased renal and circulating norepinephrine (NE), reduced myocardial NE content, increased monoaminoxidase A (MAO-A), ROS production and decreased tyrosine hydroxylase (+) nerve staining. RDN in HF animals decreased congestion in the lungs and the liver, improved load-independent cardiac function (Ees, PRSW, Ees/Ea ratio), without affecting arterial elastance or LV pressure, reduced adverse myocardial remodeling (Myh 7/6, collagen I/III ratio), decreased myocardial MAO-A and inhibited renal neprilysin activity. RDN increased myocardial expression of acetylcholinesterase (Ache) and muscarinic receptors (Chrm2), decreased circulating and renal NE, but increased myocardial NE content, restoring so autonomic control of the heart. These changes likely explain improvements in survival after RDN in this model. The results suggest that RDN has remote, load-independent and favorable intrinsic myocardial effects in the failing heart. RDN therefore could be a useful therapeutic strategy in HF.

• MeSH
• krysa rodu rattus MeSH
• ledviny * inervace   metabolismus   MeSH
• modely nemocí na zvířatech * MeSH
• myokard * metabolismus   MeSH
• noradrenalin * krev   metabolismus   MeSH
• potkani transgenní * MeSH
• remodelace komor fyziologie   MeSH
• srdce inervace   patofyziologie   MeSH
• srdeční selhání * patofyziologie   metabolismus   MeSH
• sympatektomie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

BACKGROUND AND AIMS: Right bundle branch block (RBBB) and resulting right ventricular (RV) electromechanical discoordination are thought to play a role in the disease process of subpulmonary RV dysfunction that frequently occur post-repair tetralogy of Fallot (ToF). We sought to describe this disease entity, the role of pulmonary re-valvulation, and the potential added value of RV cardiac resynchronization therapy (RV-CRT). METHODS: Two patients with repaired ToF, complete RBBB, pulmonary regurgitation, and significantly decreased RV function underwent echocardiography, cardiac magnetic resonance, and an invasive study to evaluate the potential for RV-CRT as part of the management strategy. The data were used to personalize the CircAdapt model of the human heart and circulation. Resulting Digital Twins were analysed to quantify the relative effects of RV pressure and volume overload and to predict the effect of RV-CRT. RESULTS: Echocardiography showed components of a classic RV dyssynchrony pattern which could be reversed by RV-CRT during invasive study and resulted in acute improvement in RV systolic function. The Digital Twins confirmed a contribution of electromechanical RV dyssynchrony to RV dysfunction and suggested improvement of RV contraction efficiency after RV-CRT. The one patient who underwent successful permanent RV-CRT as part of the pulmonary re-valvulation procedure carried improvements that were in line with the predictions based on his Digital Twin. CONCLUSION: An integrative diagnostic approach to RV dysfunction, including the construction of Digital Twins may help to identify candidates for RV-CRT as part of the lifetime management of ToF and similar congenital heart lesions.

• MeSH
• blokáda Tawarova raménka diagnostické zobrazování   etiologie   terapie   MeSH
• dysfunkce pravé srdeční komory * diagnostické zobrazování   etiologie   terapie   MeSH
• echokardiografie MeSH
• Fallotova tetralogie * diagnostické zobrazování   chirurgie   MeSH
• lidé MeSH
• počítačová simulace MeSH
• srdeční komory MeSH
• srdeční resynchronizační terapie * škodlivé účinky   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH