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
• Chronic Disease MeSH
• Fibrosis MeSH
• Cyclic GMP metabolism   MeSH
• Rats MeSH
• Disease Models, Animal MeSH
• Morpholines MeSH
• Oxidative Stress * drug effects   MeSH
• Rats, Sprague-Dawley * MeSH
• Rats, Transgenic MeSH
• Pyridines pharmacology   therapeutic use   MeSH
• Pyrimidines MeSH
• Ventricular Remodeling drug effects   MeSH
• Soluble Guanylyl Cyclase * metabolism   MeSH
• Signal Transduction drug effects   MeSH
• Heart Failure * drug therapy   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Embolie plodovou vodou je charakterizována náhlým kardiorespiračním kolapsem v peripartálním období. Představujeme bezprostřední management v situaci, kdy je stěžejní adekvátní rychlá reakce. Rozvoj diseminované intravaskulární koagulace potvrzuje, že diagnóza embolie plodovou vodou je vysoce pravděpodobná. Připomínáme podání kyseliny tranexamové a fibrinogenu, který je při hrazení krevních ztrát preferován před podáním plazmy s cílem snížit riziko ho selhání. Hlavními pilíři terapie jsou inotropika a plicní vazodilatancia. Přestože je podání koncentrátu C1 inhibitoru v literatuře navrhováno, reálně je jeho podání v kazuistikách popsáno výjimečně. ECMO podpora může být zvažována i u této diagnózy.

Amniotic fluid embolism is characterized by sudden cardiorespiratory collapse during labor or soon after delivery. We present immediate management when a rapid response is critical. The appearance of disseminated intravascular coagulation confirms high suspicion of the diagnosis plausibly. We remind administration of tranexamic acid and fibrinogen. Fibrinogen is preferred over plasma to minimize the risk of volume overload. Avoidance of fluid overload is an important management principle of pulmonary hypertension and right heart failure. Inotropes and pulmonary vasodilators are the mainstays of therapy. Although the therapeutic application of C1 esterase inhibitor concentrate is proposed in articles, the real application is reported sporadically. Extracorporeal membrane oxygenation can be considered.

• MeSH
• Disseminated Intravascular Coagulation etiology   MeSH
• Embolism, Amniotic Fluid * therapy   MeSH
• Fibrinogen MeSH
• Cardiopulmonary Resuscitation methods   MeSH
• Pregnancy Complications MeSH
• Tranexamic Acid pharmacology   therapeutic use   MeSH
• Humans MeSH
• Extracorporeal Membrane Oxygenation methods   MeSH
• Hypertension, Pulmonary etiology   physiopathology   MeSH
• Heart Failure etiology   MeSH
• Check Tag
• Humans 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
• Renal Insufficiency, Chronic * complications   MeSH
• Kidney Failure, Chronic * diagnosis   therapy   complications   MeSH
• Renal Dialysis adverse effects   MeSH
• Humans MeSH
• Longitudinal Studies MeSH
• Observational Studies as Topic MeSH
• Heart Failure * diagnosis   etiology   therapy   MeSH
• Water MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Clinical Trial Protocol MeSH
• Geographicals
• Czech Republic 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
• Angiotensin-Converting Enzyme Inhibitors * pharmacology   MeSH
• Phosphodiesterase 5 Inhibitors * pharmacology   MeSH
• Cardiomegaly drug therapy   MeSH
• Rats MeSH
• Ventricular Remodeling * MeSH
• Heart Failure * drug therapy   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article 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
• Glomerular Filtration Rate MeSH
• Hypertension * MeSH
• Cardio-Renal Syndrome * MeSH
• Blood Pressure MeSH
• Rats MeSH
• Kidney MeSH
• Natriuresis MeSH
• Fistula * MeSH
• Rats, Transgenic MeSH
• Renal Circulation MeSH
• Heart Failure * MeSH
• Sympathectomy MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article 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
• Rats MeSH
• Kidney * innervation   metabolism   MeSH
• Disease Models, Animal * MeSH
• Myocardium * metabolism   MeSH
• Norepinephrine * blood   metabolism   MeSH
• Rats, Transgenic * MeSH
• Ventricular Remodeling physiology   MeSH
• Heart innervation   physiopathology   MeSH
• Heart Failure * physiopathology   metabolism   MeSH
• Sympathectomy MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

BACKGROUND: Association of congestive heart failure (CHF) and chronic kidney disease (CKD) worsens the patient's prognosis and results in poor survival rate. The aim of this study was to examine if addition of endothelin type A (ETA) receptor antagonist to the angiotensin-converting enzyme inhibitor (ACEi) will bring additional beneficial effects in experimental rats. METHODS: CKD was induced by 5/6 renal mass reduction (5/6 NX) and CHF was elicited by volume overload achieved by creation of aorto-caval fistula (ACF). The follow-up was 24 weeks after the first intervention (5/6 NX). The treatment regimens were initiated 6 weeks after 5/6 NX and 2 weeks after ACF creation. RESULTS: The final survival in untreated group was 15%. The treatment with ETA receptor antagonist alone or ACEi alone and the combined treatment improved the survival rate to 64%, 71% and 75%, respectively, however, the difference between the combination and either single treatment regimen was not significant. The combined treatment exerted best renoprotection, causing additional reduction in albuminuria and reducing renal glomerular and tubulointerstitial injury as compared with ACE inhibition alone. CONCLUSIONS: Our results show that treatment with ETA receptor antagonist attenuates the CKD- and CHF-related mortality, and addition of ETA receptor antagonist to the standard blockade of RAS by ACEi exhibits additional renoprotective actions.

• MeSH
• Endothelin A Receptor Antagonists * pharmacology   therapeutic use   MeSH
• Renal Insufficiency, Chronic * complications   drug therapy   metabolism   MeSH
• Endothelin-1 metabolism   MeSH
• Angiotensin-Converting Enzyme Inhibitors pharmacology   therapeutic use   MeSH
• Rats MeSH
• Kidney MeSH
• Fistula * metabolism   MeSH
• Rats, Transgenic MeSH
• Receptor, Endothelin A metabolism   MeSH
• Renin-Angiotensin System MeSH
• Heart Failure * drug therapy   etiology   metabolism   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Heart failure (HF) is life-threatening disease due to electro-mechanical dysfunction associated with hemodynamic overload, while alterations of extracellular matrix (ECM) along with perturbed connexin-43 (Cx43) might be key factors involved. We aimed to explore a dual impact of pressure, and volume overload due to aorto-caval fistula (ACF) on Cx43 and ECM as well as effect of renin-angiotensin blockade. Hypertensive Ren-2 transgenic rats (TGR) and normotensive Hannover Sprague-Dawley rats (HSD) that underwent ACF were treated for 15-weeks with trandolapril or losartan. Blood serum and heart tissue samples of the right (RV) and left ventricles (LV) were used for analyses. ACF-HF increased RV, LV and lung mass in HSD and to lesser extent in TGR, while treatment attenuated it and normalized serum ANP, BNP-45 and TBARS. Cx43 protein and its ser368 variant along with PKCε were lower in TGR vs HSD and suppressed in both rat strains due to ACF but prevented more by trandolapril. Pro-hypertrophic PKCδ, collagen I and hydroxyproline were elevated in TGR and increased due to ACF in both rat strains. While SMAD2/3 and MMP2 levels were lower in TGR vs HSD and reduced due to ACF in both strains. Findings point out the strain-related differences in response to volume overload. Disorders of Cx43 and ECM signalling may contribute not only to HF but also to the formation of arrhythmogenic substrate. There is benefit of treatment with trandolapril and losartan indicating their pleiotropic anti-arrhythmic potential. It may provide novel input to therapy.

• MeSH
• Extracellular Matrix MeSH
• Hypertension * MeSH
• Connexin 43 genetics   MeSH
• Blood Pressure MeSH
• Rats MeSH
• Losartan pharmacology   MeSH
• Fistula * MeSH
• Rats, Sprague-Dawley MeSH
• Rats, Transgenic MeSH
• Renin MeSH
• Heart Failure * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

OBJECTIVE: Evaluation of the effect of endothelin type A (ET A ) receptor blockade on the course of volume-overload heart failure in rats with angiotensin II-dependent hypertension. METHODS: Ren-2 renin transgenic rats (TGR) were used as a model of hypertension. Heart failure was induced by creating an aorto-caval fistula (ACF). Selective ET A receptor blockade was achieved by atrasentan. For comparison, other rat groups received trandolapril, an angiotensin-converting enzyme inhibitor (ACEi). Animals first underwent ACF creation and 2 weeks later the treatment with atrasentan or trandolapril, alone or combined, was applied; the follow-up period was 20 weeks. RESULTS: Eighteen days after creating ACF, untreated TGR began to die, and none was alive by day 79. Both atrasentan and trandolapril treatment improved the survival rate, ultimately to 56% (18 of 31 animals) and 69% (22 of 32 animals), respectively. Combined ACEi and ET A receptor blockade improved the final survival rate to 52% (17 of 33 animals). The effects of the three treatment regimens on the survival rate did not significantly differ. All three treatment regimens suppressed the development of cardiac hypertrophy and lung congestion, decreased left ventricle (LV) end-diastolic volume and LV end-diastolic pressure, and improved LV systolic contractility in ACF TGR as compared with their untreated counterparts. CONCLUSION: The treatment with ET A receptor antagonist delays the onset of decompensation of volume-overload heart failure and improves the survival rate in hypertensive TGR with ACF-induced heart failure. However, the addition of ET A receptor blockade did not enhance the beneficial effects beyond those obtained with standard treatment with ACEi alone.

• MeSH
• Angiotensin II MeSH
• Atrasentan MeSH
• Endothelin-1 MeSH
• Endothelins MeSH
• Hypertension * complications   drug therapy   MeSH
• Angiotensin-Converting Enzyme Inhibitors pharmacology   MeSH
• Rats MeSH
• Fistula * MeSH
• Rats, Transgenic MeSH
• Receptor, Angiotensin, Type 1 MeSH
• Receptor, Endothelin A MeSH
• Heart Failure * drug therapy   etiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

The pressure-volume (PV) analysis is used for an accurate assessment of load-independent cardiac function and is important for the study of cardiovascular diseases and various therapeutic modalities. PV analysis is often performed on one of the ventricles, or on both ventricles but sequentially. Since both ventricles interact with each other and their functions are mutually interdependent, especially in various disease conditions such as pulmonary hypertension or heart failure, it is important to quantify the function of both ventricles at the same time. Therefore, our aim was to describe a standardized protocol for simultaneous right (RV) and left (LV) ventricle of PV analysis, including an especially controllable preload reduction manoeuver. Our second aim was to test whether simultaneous catheterization of both LV and RV is necessary for the determination of biventricular PV relationship compared to sequential measurement of both ventricles separately. In this article, we showed the feasibility and the value of simultaneous biventricular PV analysis in the measurement of contractility parameters (end-systolic pressure-volume relationship (ESPVR), ventricular pressure over time (dP/dt)max, divided by end-diastolic volume (dP/dt max-EDV)) with a comparison to the sequential measurement of the RV and LV ventricles separately. We described in detail the protocol for simultaneous biventricular PV analysis in rats using a pair of conductance-micromanometer catheters with a preload-reducing manoeuver using balloon catheter inflation in the inferior vena cava. We also described technical tips and show examples of PV loop data obtained in normotensive and hypertensive rats, with and without heart failure due to volume overload. This protocol could be useful for scientists studying hemodynamics and cardiac contractility in various models of cardiovascular diseases with a focus on biventricular differences and ventricular interdependence.

• MeSH
• Hemodynamics MeSH
• Cardiovascular Diseases * MeSH
• Myocardial Contraction physiology   MeSH
• Rats MeSH
• Heart Ventricles MeSH
• Heart Failure * MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH