Beneficial Effect of Renal Denervation on Ventricular Premature Complex Induced Cardiomyopathy.
Ontology highlight
ABSTRACT:
SUBMITTER: Yamada S
PROVIDER: S-EPMC5523999 | biostudies-other | 2017 Mar
REPOSITORIES: biostudies-other
Similar Datasets
Project description:BackgroundFrequent premature ventricular contractions (PVCs) are associated with increased risk of sudden cardiac death and can cause secondary cardiomyopathy.ObjectiveWe sought to determine the mechanism(s) responsible for prolonged refractory period and left ventricular (LV) dysfunction demonstrated in our canine model of PVC-induced cardiomyopathy.MethodsSingle myocytes were isolated from LV free wall of PVC and control canines and used for patch-clamp recording, intracellular Ca(2+) measurements, and immunocytochemistry/confocal microscopy. LV tissues adjacent to the area of myocyte isolation were used for the immunoblot quantification of protein expression.ResultsIn the PVC group, LV ejection fraction decreased from 57.6% ± 1.5% to 30.4% ± 3.1% after ≥4 months of ventricular bigeminy. Compared to control myocytes, PVC myocytes had decreased densities of both outward (transient outward current [Ito] and inward rectifier current [IK1]) and inward (L-type Ca current [ICaL]) currents, but no consistent changes in rapid or slow delayed rectifier currents. The reduction in Ito, IK1, and ICaL was accompanied by decreased protein levels of their channel subunits. The extent of reduction in Ito, IK1, and ICaL varied among PVC myocytes, creating marked heterogeneity in action potential configurations and durations. PVC myocytes showed impaired Ca-induced Ca release from the sarcoplasmic reticulum (SR), without increase in SR Ca leak or decrease in SR Ca store. This was accompanied by a decrease in dyad scaffolding protein, junctophilin-2, and loss of Cav1.2 registry with Ca-releasing channels (ryanodine receptor 2).ConclusionPVCs increase dispersion of action potential configuration/duration, a risk factor for sudden cardiac death, because of the heterogeneous reduction in Ito, IK1, and ICaL. The excitation-contraction coupling is impaired because of the decrease in ICaL and Cav1.2 misalignment with respect to ryanodine receptor 2.
| S-EPMC4252777 | biostudies-literature
Project description:BackgroundPremature ventricular complexes (PVCs) are ectopic heartbeats caused by early myocardial depolarizations, previously thought to be benign. Recent studies found high PVC burden above 24% can induce or contribute to cardiomyopathy and heart failure. We present a case of PVC-induced dilated cardiomyopathy (DCM).Case summaryA 68-year-old woman was admitted with pneumonia after an overseas trip with a preceding viral respiratory tract infection. An initial chest X-ray was suggestive of cardiomegaly. A transthoracic echocardiogram (TTE) revealed DCM with global systolic dysfunction (left ventricular ejection fraction <30%) without valvular lesions. Biochemistry and coronary angiography were normal. Clinical deterioration occurred despite medical therapy. A 24-h Holter monitoring detected 27% PVCs, which was thought to have caused DCM. As an alternative to cardiac resynchronization therapy and an implantable cardiac defibrillator for primary prevention, ablation of the PVC focus led to complete suppression of ectopy. Post-procedure TTEs and Holter monitoring showed normalized systolic function and low PVC burden.DiscussionBecause high PVC burden can lead to cardiomyopathy and heart failure, suppression of PVC should be considered to restore ventricular function for patients with structural heart disease and frequent symptomatic PVCs. This case highlights that PVCs may be a modifiable risk factor for heart failure that can be successfully treated with pharmacological therapies or catheter ablation.
| S-EPMC6458864 | biostudies-literature
Project description:BACKGROUND:This study assessed the therapeutic effects of renal sympathetic denervation (RDN) on post-myocardial infarction (MI) ventricular remodeling and sympathetic neural remodeling in dogs. The possible mechanisms and optimal time for treatment are discussed. METHODS:We randomly assigned 30 dogs to five groups: RDN 1 week before MI (RDN1w?+?MI; n?=?6), RDN 1 week after MI (MI1w?+?RDN; n?=?6), RDN 2 weeks after MI (MI2w?+?RDN; n?=?6), control (N; n?=?6), and MI (n?=?6). A canine model of myocardial infarction was established by interventional occlusion with a gelatin sponge via the femoral artery. Brain natriuretic peptide (BNP) and endothelin-1 (ET-1) levels were measured and echocardiography was performed to assess cardiac function and heart size. All dogs were killed at the end of the experiment and samples of cardiac and renal arteries were obtained. The expression of matrix metalloproteinase (MMP)-2 and MMP-9 in cardiac and of tyrosine hydroxylase (TH) in renal arteries was assessed by immunohistochemistry. Sympathetic innervations in the infarction border zone were investigated via Western blotting and real-time PCR. RESULTS:Left ventricular function in the MI group decreased significantly, while plasma BNP and ET-1 levels as well as MMP-2 and MMP-9 expression increased. Compared with the MI group, the RD groups showed significantly reduced MMP?2, MMP?9, TH, and growth-associated protein (GAP) 43 expression in the RDN1w?+?MI, MI1w?+?RDN, and MI2w?+?RDN groups was significantly improved. Additionally, the expression of TH in renal arteries decreased after RDN. CONCLUSION:RDN has preventive and therapeutic effects on post-MI ventricular remodeling and sympathetic neural remodeling. The mechanism of RDN is likely mediated through restraint of renal sympathetic nerve activity.
| S-EPMC6890580 | biostudies-literature
Project description:Mechanisms behind development of premature ventricular contraction (PVC)-induced cardiomyopathy remain unclear. PVCs may adversely modulate the autonomic nervous system to promote development of heart failure. Afferent neurons in the inferior vagal (nodose) ganglia transduce cardiac activity and modulate parasympathetic output. Effects of PVCs on cardiac parasympathetic efferent and vagal afferent neurotransmission are unknown. The purpose of this study was to evaluate effects of PVCs on vagal afferent neurotransmission and compare these effects with a known powerful autonomic modulator, myocardial ischemia. In 16 pigs, effects of variably coupled PVCs on heart rate variability (HRV) and vagal afferent neurotransmission were evaluated. Direct nodose neuronal recordings were obtained in vivo, and cardiac-related afferent neurons were identified based on their response to cardiovascular interventions, including ventricular chemical and mechanical stimuli, left anterior descending (LAD) coronary artery occlusion, and variably coupled PVCs. On HRV analysis before versus after PVCs, parasympathetic tone decreased (normalized high frequency: 83.6?±?2.8 to 72.5?±?5.3; P < 0.05). PVCs had a powerful impact on activity of cardiac-related afferent neurons, altering activity of 51% of neurons versus 31% for LAD occlusion (P < 0.05 vs. LAD occlusion and all other cardiac interventions). Both chemosensitive and mechanosensitive neurons were activated by PVCs, and their activity remained elevated even after cessation of PVCs. Cardiac afferent neural responses to PVCs were greater than any other intervention, including ischemia of similar duration. These data suggest that even brief periods of PVCs powerfully modulate vagal afferent neurotransmission, reflexly decreasing parasympathetic efferent tone.NEW & NOTEWORTHY Premature ventricular contractions (PVCs) are common in many patients and, at an increased burden, are known to cause heart failure. This study determined that PVCs powerfully modulate cardiac vagal afferent neurotransmission (exerting even greater effects than ventricular ischemia) and reduce parasympathetic efferent outflow to the heart. PVCs activated both mechano- and chemosensory neurons in the nodose ganglia. These peripheral neurons demonstrated adaptation in response to PVCs. This study provides additional data on the potential role of the autonomic nervous system in PVC-induced cardiomyopathy.
| S-EPMC6766725 | biostudies-literature
Project description:Premature ventricular contractions (PVCs) commonly coexist with cardiomyopathy. Recently, PVCs have been identified as a possible cause of cardiomyopathy. We developed a PVC-induced cardiomyopathy animal model using a novel premature pacing algorithm to assess timeframe and reversibility of this cardiomyopathy and examine the associated histopathologic abnormalities.Thirteen mongrel dogs were implanted with a specially programmed pacemaker capable of simulating ventricular extrasystoles. Animals were randomly assigned to either 12 weeks of bigeminal PVCs (n = 7) or no PVCs (control, n = 6). Continuous 24-hour Holter monitoring corroborated ventricular bigeminy in the PVC group (PVC, 49.8% versus control, < 0.01%; P<0.0001). After 12 weeks, only the PVC group had cardiomyopathy, with a significant reduction in left ventricular ejection fraction (PVC, 39.7 ± 5.4% versus control, 60.7 ± 3.8%; P < 0.0001) and an increase in left ventricular end-systolic dimension (PVC, 33.3 ± 3.5 mm versus control, 23.7 ± 3.6 mm; P < 0.001). Ventricular effective refractory period showed a trend to prolong in the PVC group. PVC-induced cardiomyopathy was resolved within 2 to 4 weeks after discontinuation of PVCs. No inflammation, fibrosis, or changes in apoptosis and mitochondrial oxidative phosphorylation were observed with PVC-induced cardiomyopathy.This novel PVC animal model demonstrates that frequent PVCs alone can induce a reversible form of cardiomyopathy in otherwise structurally normal hearts. PVC-induced cardiomyopathy lacks gross histopathologic and mitochondrial abnormalities seen in other canine models of cardiomyopathy.
| S-EPMC3175603 | biostudies-literature
Project description:BACKGROUND:Frequent premature ventricular contractions (PVCs) have been associated with PVC-induced cardiomyopathy (CM) in some patients. OBJECTIVE:The purpose of this study was to understand the cardiac consequences of different PVC burdens and the minimum burden required to induce left ventricular (LV) dysfunction. METHODS:Right ventricular apical PVCs at a coupling interval of 240 ms were introduced at different PVC burdens in 9 mongrel canines. A stepwise increase in PVC burden was implemented every 8 weeks from 0% (baseline), 7%, 14%, 25%, 33% to 50% using our premature pacing algorithm. Echocardiogram and 24-hour Holter were obtained at 4- and 8-week period for each PVC burden with a single blinded reader assessing all echocardiographic parameters including those assessed by speckle tracking imaging (EchoPAC workstation, General Electric). CM was defined as left ventricular ejection fraction (LVEF) <50% or LVEF drop >10% points. Interleukin-6 and pro-brain natriuretic peptide levels were obtained at the end of each PVC burden. RESULTS:The mean LVEF (mean heart rate) at 8 weeks for each PVC burden (0%, 7%, 14%, 33%, and 50%) were 57% ± 2.9% (85 ± 13 beats/min), 54.4% ± 3% (81 ± 10 beats/min), 53.3% ± 5% (77 ± 12 beats/min), 51.1% ± 4.2% (79 ± 14 beats/min), 47.7% ± 3.8% (80 ± 14 beats/min), and 44.7% ± 1.9% (157 ± 43 beats/min). PVC-induced CM was present in 11.1%, 44.4%, and 100% of animals with 25%, 33%, and 50% PVC burden, respectively. E/A ratio and radial strain decreased while left atrial size increased beyond 33% PVC burden. No changes in pro-brain natriuretic peptide and interleukin-6 levels were noted at any PVC burden. CONCLUSION:LV systolic function (LVEF and radial strain) declined linearly as PVC burden increased. PVC-induced CM developed in some canines with 25% and 33% PVC burden, but developed in all animals with 50% PVC burden.
| S-EPMC4762722 | biostudies-literature
Project description:Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.
| S-EPMC4686968 | biostudies-other
Project description:BACKGROUND:The presence and significance of neural remodeling in premature ventricular contraction-induced cardiomyopathy (PVC-CM) remain unknown. OBJECTIVES:This study aimed to characterize cardiac sympathovagal balance and proarrhythmia in a canine model of PVC-CM. METHODS:In 12 canines, the investigators implanted epicardial pacemakers and radiotelemetry units to record cardiac rhythm and nerve activity (NA) from the left stellate ganglion (SNA), left cardiac vagus (VNA), and arterial blood pressure. Bigeminal PVCs (200 ms coupling) were applied for 12 weeks to induce PVC-CM in 7 animals then disabled for 4 weeks to allow complete recovery of left ventricular ejection fraction (LVEF), versus 5 sham controls. RESULTS:After 12 weeks of PVCs, LVEF (p = 0.006) and dP/dT (p = 0.007) decreased. Resting SNA (p = 0.002) and VNA (p = 0.04), exercise SNA (p = 0.01), SNA response to evoked PVCs (p = 0.005), heart rate (HR) at rest (p = 0.003), and exercise (p < 0.04) increased, whereas HR variability (HRV) decreased (p = 0.009). There was increased spontaneous atrial (p = 0.02) and ventricular arrhythmias (p = 0.03) in PVC-CM. Increased SNA preceded both atrial (p = 0.0003) and ventricular (p = 0.009) arrhythmia onset. Clonidine suppressed SNA and abolished all arrhythmias. After disabling PVC for 4 weeks, LVEF (p = 0.01), dP/dT (p = 0.047), and resting VNA (p = 0.03) recovered to baseline levels. However, SNA, resting HR, HRV, and atrial (p = 0.03) and ventricular (p = 0.03) proarrhythmia persisted. There was sympathetic hyperinnervation in stellate ganglia (p = 0.02) but not ventricles (p = 0.2) of PVC-CM and recovered animals versus sham controls. CONCLUSIONS:Neural remodeling in PVC-CM is characterized by extracardiac sympathetic hyperinnervation and sympathetic neural hyperactivity that persists despite normalization of LVEF. The altered cardiac sympathovagal balance is an important trigger and substrate for atrial and ventricular proarrhythmia.
| S-EPMC7006705 | biostudies-literature
Project description:BackgroundLeft ventricular (LV) dyssynchrony caused by premature ventricular contractions (PVCs) has been proposed as a mechanism of PVC-induced cardiomyopathy. We sought to understand the impact of different PVC locations and coupling intervals (prematurity) on LV regional mechanics and global function of the PVC beat itself.Methods and resultsUsing our premature pacing algorithm, pentageminal PVCs at coupling intervals of 200 to 375 ms were delivered from the epicardial right ventricular apex, RV outflow tract, and LV free wall, as well as premature atrial contractions, from the left atrial appendage at a coupling interval of 200 ms in 7 healthy canines. LV short-axis echocardiographic images, LV stroke volume, and dP/dtmax were obtained during all ectopic beats and ventricular pacing. LV dyssynchrony was assessed by dispersion of QRS-to-peak strain (earliest-last QRS-to-peak strain) between 6 different LV segments during each of the aforementioned beats (GE, EchoPac). LV dyssynchrony was greater during long-coupled rather than short-coupled PVCs and PVCs at 375 ms compared with rapid ventricular pacing at 400 ms (P<0.0001), whereas no difference was found between PVC locations. Longer PVC coupling intervals were associated with greater stroke volume and dP/dtmax despite more pronounced dyssynchrony (P<0.001).ConclusionsPVCs with longer coupling intervals demonstrate more pronounced LV dyssynchrony, whereas PVC location has minimal impact. LV dyssynchrony cannot be attributed to prematurity or abnormal ventricular activation alone, but rather to a combination of both. This study suggests that late-coupled PVCs may cause a more severe cardiomyopathy if dyssynchrony is the leading mechanism responsible for PVC-induced cardiomyopathy.
| S-EPMC4618025 | biostudies-literature
Project description:ObjectivesRecent progress in understanding the pathogenesis of premature ventricular contraction (PVC)-induced cardiomyopathy (PIC) has suggested a key role for inflammation. The aim of this study was to evaluate the expression of messenger RNAs (mRNAs) and the protein production of interleukin-6 (IL-6), IL-10, tumor necrosis factor alpha (TNF-α) and interferon-γ (IFN-γ) and two circulating micro-RNAs related to inflammation and cardiovascular disease; miR-155 and miR-146.Materials and methodsThe study population was comprised 25 patients with PIC and 25 patients with normal left ventricular ejection fraction despite frequent PVCs. TNF-α, IL-6, IL10, and IFN-γ levels were evaluated in peripheral blood mononuclear cells (PBMCs) by flow cytometry and their mRNAs were assessed by real time PCR. We analyzed circulating levels of these cytokines by enzyme linked immunosorbent assay (ELISA). Two circulating micro-RNAs, miR-155 and miR-146a, were also investigated.ResultsThe flow cytometry findings showed that the median fluorescence intensity (MFI) of antibodies reacted with the IL-6 and TNF-α were higher in PIC group than the control group (P-value<0.001). In ELISA, the levels of IL-6 (P-value<0.001) and TNF-α (P-value <0.001) and in RT-PCR the relative expression levels of IL-6 (P-value<0.001) and TNF-α (P-value<0.001) were significantly higher in the PIC group. The relative expression levels of miR-155 and miR-146a were not significantly different between 2 groups (P-value>0.05).ConclusionIn our patients with PIC, there was an elevation in the expression levels of IL-6 and TNF-α in PBMCs. This finding may provide further insights into the inflammatory pathways involved in PIC.
| S-EPMC6885395 | biostudies-literature