Combination of chronic kidney disease (CKD) and heart failure (HF) results in extremely high morbidity and mortality. The current guideline-directed medical therapy is rarely effective and new therapeutic approaches are urgently needed. The study was designed to examine if renal denervation (RDN) will exhibit long-standing beneficial effects on the HF- and CKD-related morbidity and mortality. Fawn-hooded hypertensive rats (FHH) served as a genetic model of CKD and fawn-hooded low-pressure rats (FHL) without CKD served as controls. HF was induced by creation of aorto-caval fistula (ACF). RDN was performed 28 days after creation of ACF and the follow-up period was 70 days. ACF FHH subjected to sham-RDN had survival rate of 34 % i.e. significantly lower than 79 % observed in sham-denervated ACF FHL. RDN did not improve the condition and the final survival rate, both in ACF FHL and in ACF FHH. In FHH basal albuminuria was markedly higher than in FHL, and further increased throughout the study. RDN did not lower albuminuria and did not reduce renal glomerular damage in FHH. In these rats creation of ACF resulted in marked bilateral cardiac hypertrophy and alterations of cardiac connexin-43, however, RDN did not modify any of the cardiac parameters. Our present results further support the notion that kidney damage aggravates the HF-related morbidity and mortality. Moreover, it is clear that in the ACF FHH model of combined CKD and HF, RDN does not exhibit any important renoprotective or cardioprotective effects and does not reduce mortality. Key words Chronic kidney disease, Heart failure, Renal denervation, Fawn-hooded hypertensive rats.
- MeSH
- denervace MeSH
- hypertenze * chirurgie MeSH
- kardiorenální syndrom * etiologie patofyziologie MeSH
- krysa rodu rattus MeSH
- ledviny * inervace MeSH
- modely nemocí na zvířatech MeSH
- srdeční selhání MeSH
- sympatektomie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata 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
Renální sympatická denervace (RDN) je metodou, která zažila svůj vzestup i částečný pád v léčbě farmakologicky nekontrolovatelné arteriální hypertenze a jejíž pevné místo v léčebném schématu tohoto onemocnění nebylo stále ještě definováno. Ovlivnění sympatické aktivity se však nachází v centru zájmu i při léčbě řady dalších kardiovaskulárních onemocnění. Patofyziologicky zcela jistě u chronického srdečního selhání, fibrilace síní, některých komorových arytmií a (do větší či menší míry) u některých dalších onemocnění. Cílem této stati je shrnout současné poznatky o přínosu RDN v léčbě výše zmíněných onemocnění.
Renal sympathetic denervation (RDN) is a method that has experienced its rise and fall in the treatment of pharmacologically-resistant essential arterial hypertension, and its firm indications for the treatment of this disease have not been defined yet. Modification of sympathetic activity, however, is in the centre of attention in the treatment of some other pathological conditions. From the pathophysiologic point of view, it is certainly so in the treatment of heart failure, atrial fibrillation, and some types of ventricular arrhythmias, as well as in the case of some other diseases, to a greater or lesser extent. The aim of this article is to review the present knowledge on the contribution of RDN in the treatment of the above-mentioned diseases.
- MeSH
- denervace metody MeSH
- hypertenze chirurgie terapie MeSH
- kardiovaskulární nemoci chirurgie etiologie MeSH
- katetrizační ablace metody MeSH
- ledviny * inervace MeSH
- lidé MeSH
- nemoci srdce chirurgie etiologie MeSH
- noradrenalin krev MeSH
- sympatektomie * metody MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Kašel je nejčastějším příznakem onemocnění dýchacích cest, ale je také jedním z nedůležitějším obranných mechanismů lidského organismu. Často je obtížné stanovit, kdy tento obranný reflex přestane plnit svou fyziologickou úlohu a stane se patologickým. Kašel není diagnózou, je symptomem různých onemocnění a jejich kombinací a je nejčastějším příznakem chorob respiračního ústrojí. Často se definice chronického kašle zaměňuje s definici chronické bronchitidy. Chronická bronchitida je chronické, progresivní onemocnění, terapeuticky obtížně ovlivnitelné. Navzdory veškerému úsilí zůstávají pacienti vysoce symptomatičtí. V současné době je zkoumána řada nových bronchoskopických léčebných postupů: použití kryospreje, bronchiální rheoplastika, balónková desobstrukce a cílená plicní denervace. Cílem těchto metod je zničení hyperplastických pohárkových buněk, nadbytečných submukózních žláz a regulace tonu hladkého svalstva. Tyto léčebné modality jsou v rané fází klinického výzkumu, ale prokázaly zlepšení příznaků chronické bronchitidy a snížení frekvence exacerbací. K vyhodnocení trvanlivosti léčby jsou ale zapotřebí větší randomizované kontrolované studie.
Cough is the most common symptom of respiratory diseases, but it is also one of the most important defense mechanisms of human body. It is often difficult to determine when this defensive reflex ceases to fulfill its physiological role and becomes pathological. Cough is not a diagnosis, it is just a symptom of various diseases and their combination, it is the most common symptom of diseases of the respiratory system. Often the definition of chronic cough is confused with the definition of chronic bronchitis. Chronic bronchitis is a chronic, progressive disease that is difficult to influence with therapeutics. Despite great efforts, patients remain highly symptomatic. Several new bronchoscopic treatments are currently being investigated: the use of cryospray, bronchial rheoplasty, balloon desobstruction and targeted pulmonary denervation. The aim of these methods is the destruction of hyperplastic goblet cells, redundant submucosal glands and regulation of smooth muscle tone. These treatment modalities are in the early stages of clinical research but have been shown to improve symptoms of chronic bronchitis and reduce the frequency of exacerbations. However, larger randomized controlled trials are needed to evaluate the durability of treatment.
OBJECTIVES: This study sought to determine the impact of adjunctive renal sympathetic denervation to catheter ablation in patients with atrial fibrillation (AF) and history of hypertension. BACKGROUND: There are limited data regarding the impact of upstream adjunctive renal sympathetic denervation (RSDN) to pulmonary vein isolation (PVI) in patients with symptomatic atrial fibrillation (AF) and hypertension. METHODS: The data for this study were obtained from 2 prospective randomized pilot studies, the HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-1 (n = 30) and HFIB (Adjunctive Renal Denervation to Modify Hypertension and Sympathetic tone as Upstream Therapy in the Treatment of Atrial Fibrillation)-2 (n = 50) studies, and we performed a meta-analysis including all published studies comparing RSDN+PVI versus PVI alone up to January 25, 2020, in patients with AF and hypertension. RESULTS: At 24 months, AF recurrence occurred in 53% and 38% in the PVI and PVI+RSDN groups (p = 0.43) in the HFIB-1 study, respectively, and 27% and 25% in the PVI and PVI+RSDN groups (p = 0.80) in the HFIB-2 study, respectively. When combined in a meta-analysis including 6 studies (n = 725), adjunctive RSDN significantly decreased the risk of AF recurrence (risk ratio [RR]: 0.68; 95% confidence interval [CI]: 0.55 to 0.83; p = 0.0002; I2 = 0%) when compared with PVI. Six renal artery complications occurred in the HFIB-1 study and none occurred in the HFIB-2 study with RSDN. However, in the meta-analysis, there were no significant differences in overall complications between both groups (RR: 1.43; 95% CI: 0.63 to 3.22; p = 0.40; I2 = 7%). When compared with baseline, RDSN significantly reduced the systolic blood pressure (-12.1 mm Hg; 95% CI: -20.9 to -3.3 mm Hg; p < 0.007; I2 = 99%) and diastolic blood pressure (-5.60 mm Hg; 95% CI: -10.05 to -1.10 mm Hg; p = 0.01; I2 = 98%) on follow-up. CONCLUSIONS: The pilot HFIB-1 and HFIB-2 studies did not demonstrate a benefit with RSDN as an adjunctive upstream therapy during PVI. However, in the meta-analysis, adjunctive RSDN to PVI appears to be safe, and improves clinical outcomes in AF patients with a history of hypertension.
- MeSH
- fibrilace síní * chirurgie MeSH
- katetrizační ablace * MeSH
- lidé MeSH
- pilotní projekty MeSH
- prospektivní studie MeSH
- randomizované kontrolované studie jako téma MeSH
- recidiva MeSH
- sympatektomie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
- práce podpořená grantem MeSH
- MeSH
- ablace škodlivé účinky MeSH
- acitretin aplikace a dávkování MeSH
- amputace MeSH
- angioplastika MeSH
- antiflogistika nesteroidní terapeutické užití MeSH
- biologická terapie * MeSH
- cyklosporin aplikace a dávkování MeSH
- dermatologické látky aplikace a dávkování MeSH
- dospělí MeSH
- etanercept aplikace a dávkování MeSH
- fototerapie MeSH
- gangréna chirurgie MeSH
- humanizované monoklonální protilátky aplikace a dávkování MeSH
- inhibitory agregace trombocytů terapeutické užití MeSH
- klindamycin terapeutické užití MeSH
- komorbidita MeSH
- lidé MeSH
- methotrexát aplikace a dávkování škodlivé účinky MeSH
- neúspěšná terapie MeSH
- obezita komplikace MeSH
- palec nohy chirurgie patologie MeSH
- progrese nemoci MeSH
- psoriáza * farmakoterapie komplikace terapie MeSH
- rizikové faktory MeSH
- sympatektomie chemická MeSH
- výsledek terapie MeSH
- zarostlé nehty chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
Background: The coincidence of congestive heart failure (CHF) and chronic kidney disease (CKD) results in poor survival rate. The aim of the study was to examine if renal denervation (RDN) would improve the survival rate in CHF induced by creation of aorto-caval fistula (ACF).Methods: Fawn-hooded hypertensive rats (FHH), a genetic model of spontaneous hypertension associated with CKD development, were used. Fawn-hooded low-pressure rats (FHL), without CKD, served as controls. RDN was performed 4 weeks after creation of ACF and the follow-up period was 10 weeks.Results: We found that intact (non-denervated) ACF FHH exhibited survival rate of 58.8% (20 out of 34 rats), significantly lower than in intact ACF FHL (81.3%, 26/32 rats). In intact ACF FHL albuminuria remained stable throughout the study, whereas in ACF FHH it increased significantly, up to a level 40-fold higher than the basal values. ACF FHL did not show increases in renal glomerular and tubulointerstitial injury as compared with FHL, while ACF FHH exhibited marked increases in kidney injury as compared with FHH. RDN did not improve the survival rate in either ACF FHL or ACF FHH and did not alter the course of albuminuria in ACF FHL. RDN attenuated the albuminuria, but did not reduce the kidney injury in ACF FHH.Conclusions: Our present results support the notion that even modest CKD increases CHF-related mortality. RDN did not attenuate CHF-dependent mortality in ACF FHH, it delayed the progressive rise in albuminuria, but it did not reduce the degree of kidney injury.
OBJECTIVE: We examined if renal denervation (RDN) attenuates the progression of aortocaval fistula (ACF)-induced heart failure or improves renal hemodynamics in Ren-2 transgenic rats (TGR), a model of angiotensin II (ANG II)-dependent hypertension. METHODS: Bilateral RDN was performed 1 week after creation of ACF. The animals studied were ACF TGR and sham-operated controls, and both groups were subjected to RDN or sham denervation. In separate groups, renal artery blood flow (RBF) responses were determined to intrarenal ANG II (2 and 8 ng), norepinephrine (NE) (20 and 40 ng) and acetylcholine (Ach) (10 and 40 ng) 3 weeks after ACF creation. RESULTS: In nondenervated ACF TGR, the final survival rate was 10 versus 50% in RDN rats. RBF was significantly lower in ACF TGR than in sham-operated TGR (6.2 ± 0.3 vs. 9.7 ± 0.5 mL min-1 g-1, p < 0.05), the levels unaffected by RDN. Both doses of ANG II decreased RBF more in ACF TGR than in sham-operated TGR (-19 ± 3 vs. -9 ± 2% and -47 ± 3 vs. -22 ± 2%, p < 0.05 in both cases). RDN did not alter RBF responses to the lower dose, but increased it to the higher dose of ANG II in sham-operated as well as in ACF TGR. NE comparably decreased RBF in ACF TGR and sham-operated TGR, and RDN increased RBF responsiveness. Intrarenal Ach increased RBF significantly more in ACF TGR than in sham-operated TGR (29 ± 3 vs. 17 ± 3%, p < 0.05), the changes unaffected by RDN. ACF creation induced marked bilateral cardiac hypertrophy and lung congestion, both attenuated by RDN. In sham-operated but not in ACF TGR, RDN significantly decreased mean arterial pressure. CONCLUSION: The results show that RDN significantly improved survival rate in ACF TGR; however, this beneficial effect was not associated with improvement of reduced RBF or with attenuation of exaggerated renal vascular responsiveness to ANG II.
- MeSH
- angiotensin II metabolismus MeSH
- arteriovenózní píštěl komplikace MeSH
- hypertenze komplikace genetika metabolismus MeSH
- krysa rodu rattus MeSH
- ledviny inervace chirurgie MeSH
- potkani Sprague-Dawley MeSH
- potkani transgenní MeSH
- renin genetika MeSH
- srdeční selhání komplikace genetika metabolismus terapie MeSH
- sympatektomie * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
