Retencia tekutín s kongesciou, hypervolémiou a objemovým preťažením srdca je pravidelnou súčasťou syndrómu pokročilého srdcového zlyhávania. Podstatou účinku diuretík je zvýšenie tvorby moču v dôsledku zásahu do transportných pochodov chloridov, nátria, kália a vody na úrovni tubulov a zberných kanálikov v obličkách. Článok sa zaoberá patofyziologickými a klinickými dôsledkami kongescie, taktikou diuretickej liečby a jej vplyvom na morbiditu a mortalitu pacientov so srdcovým zlyhávaním.

Retention of fluid with congestion, hypervolemia, and volume overload of heart are regular components of syndrome of advanced heart failure. The principle of the diuretic effect is the increase of urine formation as a consequence of the interference with transport mechanisms of chlorides, sodium, potassium and water on the level of tubuli and collecting ducts in kidneys. The article discusses pathophysiological and clinical consequences of congestion, strategies of diuretic therapy and its influence on morbidity and mortality of patients with heart failure.

• MeSH
• diuretika farmakokinetika   farmakologie   klasifikace   MeSH
• inhibitory symportérů pro chlorid sodný farmakokinetika   MeSH
• lidé MeSH
• osmotická diuretika farmakokinetika   klasifikace   MeSH
• srdeční selhání farmakoterapie   MeSH
• Check Tag
• lidé MeSH

Mechanisms of right ventricular (RV) dysfunction in heart failure (HF) are poorly understood. RV response to volume overload (VO), a common contributing factor to HF, is rarely studied. The goal was to identify interventricular differences in response to chronic VO. Rats underwent aorto-caval fistula (ACF)/sham operation to induce VO. After 24 weeks, RV and left ventricular (LV) functions, gene expression and proteomics were studied. ACF led to biventricular dilatation, systolic dysfunction and hypertrophy affecting relatively more RV. Increased RV afterload contributed to larger RV stroke work increment compared to LV. Both ACF ventricles displayed upregulation of genes of myocardial stress and metabolism. Most proteins reacted to VO in a similar direction in both ventricles, yet the expression changes were more pronounced in RV (pslope: < 0.001). The most upregulated were extracellular matrix (POSTN, NRAP, TGM2, CKAP4), cell adhesion (NCAM, NRAP, XIRP2) and cytoskeletal proteins (FHL1, CSRP3) and enzymes of carbohydrate (PKM) or norepinephrine (MAOA) metabolism. Downregulated were MYH6 and FAO enzymes. Therefore, when exposed to identical VO, both ventricles display similar upregulation of stress and metabolic markers. Relatively larger response of ACF RV compared to the LV may be caused by concomitant pulmonary hypertension. No evidence supports RV chamber-specific regulation of protein expression in response to VO.

• MeSH
• extracelulární matrix - proteiny genetika   metabolismus   MeSH
• krysa rodu rattus MeSH
• molekuly buněčné adheze genetika   metabolismus   MeSH
• myokard metabolismus   MeSH
• potkani Sprague-Dawley MeSH
• protein-glutamin:amin-gama-glutamyltransferasa 2 MeSH
• proteom genetika   metabolismus   MeSH
• pyruvátkinasa genetika   metabolismus   MeSH
• remodelace komor * MeSH
• srdeční komory metabolismus   patologie   patofyziologie   MeSH
• srdeční selhání metabolismus   patologie   patofyziologie   MeSH
• tepový objem MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chronic volume overload leads to cardiac hypertrophy and later to heart failure (HF), which are both associated with increased risk of cardiac arrhythmias. The goal of this study was to describe changes in myocardial morphology and to characterize arrhythmogenic substrate in rat model of developing HF due to volume overload. An arteriovenous fistula (AVF) was created in male Wistar rats between the inferior vena cava and abdominal aorta using needle technique. Myocardial morphology, tissue fibrosis, and connexin43 distribution, localization and phosphorylation were examined using confocal microscopy and Western blotting in the stage of compensated hypertrophy (11 weeks), and decompensated HF (21 weeks). Heart to body weight (BW) ratio was 89% and 133% higher in AVF rats at 11 and 21 weeks, respectively. At 21 weeks but not 11 weeks, AVF rats had pulmonary congestion (increased lung to BW ratio) indicating presence of decompensated HF. The myocytes in left ventricular midmyocardium were significantly thicker (+8% and +45%) and longer (+88% and +97%). Despite extensive hypertrophy, there was no excessive fibrosis in the AVF ventricles. Distribution and localization of connexin43 were similar between groups, but its phosphorylation was significantly lower in AVF hearts at 21st week, but not 11th week, suggesting that HF, rather than hypertrophy contributes to the connexin43 hypophosphorylation. In conclusion, volume overload leads to extensive eccentric hypertrophy, but not to myocardial fibrosis. Increased vulnerability to arrhythmia in this HF model is possibly related to gap junction remodeling with hypophosphorylation of connexin43.

• MeSH
• arteriovenózní píštěl komplikace   metabolismus   patologie   MeSH
• chronická nemoc MeSH
• fosforylace MeSH
• kardiomegalie komplikace   metabolismus   patologie   MeSH
• konexin 43 biosyntéza   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• potkani Wistar MeSH
• srdeční arytmie etiologie   metabolismus   patologie   MeSH
• srdeční selhání metabolismus   patologie   MeSH
• tepový objem fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• srovnávací studie MeSH

BACKGROUND: There are only few studies documenting the long-term outcome of aorto-caval fistula (ACF) in rats, a model of volume overload heart failure (HF). The aim of the present study was to describe HF-related morbidity and mortality, and to examine the relation between cardiac hypertrophy and survival. METHODS: Adult male Wistar rats underwent needle ACF or sham operation and 71 animals surviving the acute procedure with patent ACF were followed for 52 weeks. RESULTS: By the end of the study, 72% of the ACF animals deceased and 82% developed HF signs. Of the HF rats, 65% died (median: 3 weeks after HF onset). Before death, body weight increased by 9% followed by a final drop. 28% ACF rats died suddenly, without preceding HF. Sudden death occurred earlier and in the rats with a trend to larger hearts (p = 0.07). In the whole ACF cohort, heart weight (heart weight/body weight ratio) was inversely associated with the length of survival (r = -0.51, p < 0.001). CONCLUSION: The median survival of ACF Wistar rats is 43 weeks, longer than reported in other rat strains. Increased heart weight is associated with higher mortality and a significant number of animals die suddenly.

• MeSH
• aorta abdominalis abnormality   MeSH
• arteriovenózní píštěl komplikace   mortalita   patofyziologie   MeSH
• kardiomegalie etiologie   mortalita   patofyziologie   MeSH
• krysa rodu rattus MeSH
• míra přežití trendy   MeSH
• potkani Wistar MeSH
• srdeční selhání etiologie   mortalita   patofyziologie   MeSH
• vena cava inferior abnormality   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Metabolic interactions between adipose tissue and the heart may play an active role in progression of heart failure (HF). The aim of the study was to examine changes in myocardial and adipose tissue metabolism and gene expression in a rat HF model induced by chronic volume overload. HF was induced by volume overload from aorto-caval fistula (ACF) in 3-month-old male Wistar rats and animals were studied in the phase of decompensated HF (22nd week). HF rats showed marked eccentric cardiac hypertrophy, pulmonary congestion, increased LV end-diastolic pressure, and intraabdominal fat depletion. HF rats had preserved glucose tolerance, but increased circulating free fatty acids (FFA) and attenuated insulin response during oral glucose challenge. Isolated organ studies showed preserved responsiveness of adipose tissue lipolysis and lipogenesis to epinephrine and insulin in ACF. The heart of HF animals had markedly reduced triglyceride content (almost to half of controls), attenuated anti-oxidative reserve (GSH/GSSG), upregulated HF markers (ANP, periostin, thrombospondin-4), specific signaling pathways (Wnt, TGF-β), and downregulated enzymes of mitochondrial fatty acid oxidation, citric acid cycle, and respiratory chain. Adipose tissue transcription profiling showed upregulated receptor for gastric inhibitory polypeptide. In conclusion, ACF-induced HF model displays several deregulations of systemic metabolism. Despite elevation of systemic FFAs, myocardial triglycerides are low and insulin levels are attenuated, arguing against a role of lipotoxicity or insulin resistance in this model. Attenuated postprandial insulin response and relative lack of its antilipolytic effects may facilitate intraabdominal fat depletion observed in ACF-HF animals.

• MeSH
• aorta chirurgie   MeSH
• arteriovenózní píštěl MeSH
• arteriovenózní zkrat MeSH
• biologické markery metabolismus   MeSH
• epididymis metabolismus   patologie   MeSH
• glukózový toleranční test MeSH
• glutathion metabolismus   MeSH
• hemodynamika MeSH
• inzulin krev   MeSH
• játra patologie   MeSH
• kardiomyocyty metabolismus   patologie   MeSH
• krysa rodu rattus MeSH
• kyseliny mastné neesterifikované krev   MeSH
• látky reagující s kyselinou thiobarbiturovou metabolismus   MeSH
• ledviny patologie   MeSH
• metabolismus lipidů MeSH
• myokard metabolismus   patologie   MeSH
• oxidační stres MeSH
• plíce patologie   MeSH
• potkani Wistar MeSH
• remodelace komor MeSH
• srdce patofyziologie   MeSH
• srdeční selhání metabolismus   patologie   patofyziologie   MeSH
• stanovení celkové genové exprese MeSH
• superoxiddismutasa metabolismus   MeSH
• tuková tkáň metabolismus   patologie   MeSH
• velikost orgánu MeSH
• venae cavae chirurgie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Advanced HF (heart failure) is associated with altered substrate metabolism. Whether modification of substrate use improves the course of HF remains unknown. The antihyperglycaemic drug MET (metformin) affects substrate metabolism, and its use might be associated with improved outcome in diabetic HF. The aim of the present study was to examine whether MET would improve cardiac function and survival also in non-diabetic HF. Volume-overload HF was induced in male Wistar rats by creating ACF (aortocaval fistula). Animals were randomized to placebo/MET (300 mg·kg(-1) of body weight·day(-1), 0.5% in food) groups and underwent assessment of metabolism, cardiovascular and mitochondrial functions (n=6-12/group) in advanced HF stage (week 21). A separate cohort served for survival analysis (n=10-90/group). The ACF group had marked cardiac hypertrophy, increased LVEDP (left ventricular end-diastolic pressure) and lung weight confirming decompensated HF, increased circulating NEFAs (non-esterified 'free' fatty acids), intra-abdominal fat depletion, lower glycogen synthesis in the skeletal muscle (diaphragm), lower myocardial triacylglycerol (triglyceride) content and attenuated myocardial (14)C-glucose and (14)C-palmitate oxidation, but preserved mitochondrial respiratory function, glucose tolerance and insulin sensitivity. MET therapy normalized serum NEFAs, decreased myocardial glucose oxidation, increased myocardial palmitate oxidation, but it had no effect on myocardial gene expression, AMPK (AMP-activated protein kinase) signalling, ATP level, mitochondrial respiration, cardiac morphology, function and long-term survival, despite reaching therapeutic serum levels (2.2±0.7 μg/ml). In conclusion, MET-induced enhancement of myocardial fatty acid oxidation had a neutral effect on cardiac function and survival. Recently reported cardioprotective effects of MET may not be universal to all forms of HF and may require AMPK activation or ATP depletion. No increase in mortality on MET supports its safe use in diabetic HF.

• MeSH
• analýza přežití MeSH
• glykogen metabolismus   MeSH
• hemodynamika účinky léků   MeSH
• hypoglykemika krev   terapeutické užití   MeSH
• krevní glukóza metabolismus   MeSH
• krysa rodu rattus MeSH
• metabolismus lipidů účinky léků   MeSH
• metformin krev   terapeutické užití   MeSH
• modely nemocí na zvířatech MeSH
• myokard metabolismus   patologie   MeSH
• plíce patologie   MeSH
• potkani Wistar MeSH
• preklinické hodnocení léčiv MeSH
• proteinkinasy metabolismus   MeSH
• srdeční mitochondrie fyziologie   MeSH
• srdeční selhání farmakoterapie   patofyziologie   ultrasonografie   MeSH
• tělesná hmotnost účinky léků   MeSH
• velikost orgánu účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články 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

PURPOSE OF REVIEW: A substantial proportion of patients with heart failure have preserved ejection fraction. Though patients with preserved ejection fraction experience a substantial burden of morbidity and mortality, the understanding of heart failure pathophysiology in this group remains incomplete and evidence-based therapeutic options are limited. RECENT FINDINGS: The prevalence of heart failure in patients with preserved ejection fraction is increasing and prognosis in this population remains poor despite modern medical therapy. Though diastolic dysfunction is typically present, increasing evidence suggests that extracardiac factors such as renal dysfunction and enhanced central aortic stiffness may play an important role in the development and progression of heart failure symptoms. Results of the first randomized, controlled clinical trials in this population suggest a possible therapeutic role for renin-angiotensin system blockade in reducing heart failure-associated morbidity, but there is still no evidence-supported strategy for reducing mortality in this population. SUMMARY: Though the epidemiology and impact of heart failure with preserved ejection fraction are increasingly clear, consensus regarding pathophysiology and the optimal therapeutic approach is still lacking. Pending completion of additional therapeutic trials in this population, treatment remains largely empiric and focused on optimizing myocardial performance in diastole by control of blood pressure, restoration or maintenance of sinus rhythm, and relief of volume overload.

• MeSH
• diastola MeSH
• lidé MeSH
• srdeční selhání diagnóza   patofyziologie   terapie   MeSH
• tepový objem MeSH
• Check Tag
• lidé MeSH

Extracorporeal life support (ECLS) is a treatment modality that provides prolonged blood circulation, gas exchange and can partially support or fully substitute functions of heart and lungs in patients with severe but potentially reversible cardiopulmonary failure refractory to conventional therapy. Due to high-volume bypass, the extracorporeal flow is interacting with native cardiac output. The pathophysiology of circulation and ECLS support reveals significant effects on arterial pressure waveforms, cardiac hemodynamics, and myocardial perfusion. Moreover, it is still subject of research, whether increasing stroke work caused by the extracorporeal flow is accompanied by adequate myocardial oxygen supply. The left ventricular (LV) pressure-volume mechanics are reflecting perfusion and loading conditions and these changes are dependent on the degree of the extracorporeal blood flow. By increasing the afterload, artificial circulation puts higher demands on heart work with increasing myocardial oxygen consumption. Further, this can lead to LV distention, pulmonary edema, and progression of heart failure. Multiple methods of LV decompression (atrial septostomy, active venting, intra-aortic balloon pump, pulsatility of flow) have been suggested to relieve LV overload but the main risk factors still remain unclear. In this context, it has been recommended to keep the rate of circulatory support as low as possible. Also, utilization of detailed hemodynamic monitoring has been suggested in order to avoid possible harm from excessive extracorporeal flow.

• MeSH
• fyziologická adaptace fyziologie   MeSH
• hemodynamika MeSH
• lidé MeSH
• mimotělní membránová oxygenace metody   MeSH
• podpůrné srdeční systémy * MeSH
• srdce fyziologie   MeSH
• srdeční selhání patofyziologie   terapie   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