ventricular arrhythmogenesis
Recently Published Documents


TOTAL DOCUMENTS

65
(FIVE YEARS 19)

H-INDEX

16
(FIVE YEARS 2)

2021 ◽  
Vol 12 ◽  
Author(s):  
Aulia Khamas Heikhmakhtiar ◽  
Abrha Abebe Tekle ◽  
Ki Moo Lim

Myocardial fibrosis is an integral component of most forms of heart failure. Clinical and computational studies have reported that spatial fibrosis pattern and fibrosis amount play a significant role in ventricular arrhythmogenicity. This study investigated the effect of the spatial distribution of fibrosis and fibrosis amount on the electrophysiology and mechanical performance of the human ventricles. Seventy-five fibrosis distributions comprising diffuse, patchy, and compact fibrosis types that contain 10–50% fibrosis amount were generated. The spatial fibrosis distribution was quantified using the fibrosis entropy (FE) metric. Electrical simulations under reentry conditions induced using the S1–S2 protocol were conducted to investigate the fibrosis arrhythmogenicity. We also performed mechanical simulations to examine the influence of the fibrosis amount and the spatial distribution of fibrosis on the pumping efficacy of the LV. We observed that the mean FE of the compact type is the largest among the three types. The electrical simulation results revealed that the ventricular arrhythmogenicity of diffuse fibrosis depends on the fibrosis amount and marginally on the spatial distribution of fibrosis. Meanwhile, the ventricular arrhythmogenicity of the compact and patchy fibrosis pattern is more reliant on the spatial distribution of fibrosis than on the fibrosis amount. The average number of phase singularities (PSs) in the compact fibrosis pattern was the highest among the three patterns of fibrosis. The diffuse type of fibrosis has the lowest average number of PSs than that in the patchy and compact fibrosis. The reduction in the stroke volume (SV) showed high influence from the electrical instabilities induced by the fibrosis amount and pattern. The compact fibrosis exhibited the lowest SV among the three patterns except in the 40% fibrosis amount. In conclusion, the fibrosis pattern is as crucial as the fibrosis amount for sustaining and aggravating ventricular arrhythmogenesis.


2021 ◽  
Vol 116 (1) ◽  
Author(s):  
Dongze Zhang ◽  
Wenfeng Hu ◽  
Huiyin Tu ◽  
Bryan T. Hackfort ◽  
Bin Duan ◽  
...  

AbstractCardiac sympathetic overactivation is involved in arrhythmogenesis in patients with chronic heart failure (CHF). Inflammatory infiltration in the stellate ganglion (SG) is a critical factor for cardiac sympathoexcitation in patients with ventricular arrhythmias. This study aims to investigate if macrophage depletion in SGs decreases cardiac sympathetic overactivation and ventricular arrhythmogenesis in CHF. Surgical ligation of the coronary artery was used for induction of CHF. Clodronate liposomes were microinjected into bilateral SGs of CHF rats for macrophage depletion. Using cytokine array, immunofluorescence staining, and Western blot analysis, we found that macrophage expansion and expression of TNFα and IL-1β in SGs were markedly increased in CHF rats. Flow cytometry data confirmed that the percentage of macrophages in SGs was higher in CHF rats than that in sham rats. Clodronate liposomes significantly reduced CHF-elevated proinflammatory cytokine levels and macrophage expansion in SGs. Clodronate liposomes also reduced CHF-increased N-type Ca2+ currents and excitability of cardiac sympathetic postganglionic neurons and inhibited CHF-enhanced cardiac sympathetic nerve activity. ECG data from 24-h, continuous telemetry recording in conscious rats demonstrated that clodronate liposomes not only restored CHF-induced heterogeneity of ventricular electrical activities, but also decreased the incidence and duration of ventricular tachycardia/fibrillation in CHF. Macrophage depletion with clodronate liposomes attenuated CHF-induced cardiac sympathetic overactivation and ventricular arrhythmias through reduction of macrophage expansion and neuroinflammation in SGs.


2021 ◽  
Author(s):  
Zhenwei Pan ◽  
Gen-Long Xue ◽  
Yang Zhang ◽  
Jiming Yang ◽  
Ying Yang ◽  
...  

Abstract Dystrophin is a critical interacting protein of Nav1.5 that determines its membrane anchoring in cardiomyocytes. The study aims to explore whether lncRNA-DACH1(lncDACH1) can regulate the distribution of Nav1.5 by binding to dystrophin and participate in ventricular arrhythmogenesis. LncDACH1 was confirmed to bind to dystrophin. Cardiomyocyte-specific transgenic overexpression of lncDACH1(lncDACH1-TG) reduced the membrane distribution of dystrophin and Nav1.5 in cardiomyocytes. The opposite data were collected from lncDACH1 cardiomyocyte conditional knockout (lncDACH1-CKO) mice. Moreover, increased ventricular arrhythmia susceptibility was observed in lncDACH1-TG mice in vivo and ex vivo. The conservative fragment of lncDACH1 inhibited membrane distribution of dystrophin and Nav1.5 and promoted the inducibility of ventricular arrhythmia. Upregulation of dystrophin in lncDACH1-TG mice rescued the impaired membrane distribution of dystrophin and Nav1.5. The human homologue of lncDACH1 inhibited the membrane distribution of Nav1.5 in human iPS-differentiated cardiomyocytes. Collectively, lncDACH1 regulates Nav1.5 membrane distribution by binding to dystrophin and participates in ventricular arrhythmogenesis.


2021 ◽  
Vol 134 (3) ◽  
pp. 405-420
Author(s):  
Yukiko Omura ◽  
Jasmine P. Kipke ◽  
Siamak Salavatian ◽  
Andrew Shea Afyouni ◽  
Christian Wooten ◽  
...  

Background Cardiac sympathoexcitation leads to ventricular arrhythmias. Spinal anesthesia modulates sympathetic output and can be cardioprotective. However, its effect on the cardio-spinal reflexes and network interactions in the dorsal horn cardiac afferent neurons and the intermediolateral nucleus sympathetic neurons that regulate sympathetic output is not known. The authors hypothesize that spinal bupivacaine reduces cardiac neuronal firing and network interactions in the dorsal horn–dorsal horn and dorsal horn–intermediolateral nucleus that produce sympathoexcitation during myocardial ischemia, attenuating ventricular arrhythmogenesis. Methods Extracellular neuronal signals from the dorsal horn and intermediolateral nucleus neurons were simultaneously recorded in Yorkshire pigs (n = 9) using a 64-channel high-density penetrating microarray electrode inserted at the T2 spinal cord. Dorsal horn and intermediolateral nucleus neural interactions and known markers of cardiac arrhythmogenesis were evaluated during myocardial ischemia and cardiac load–dependent perturbations with intrathecal bupivacaine. Results Cardiac spinal neurons were identified based on their response to myocardial ischemia and cardiac load–dependent perturbations. Spinal bupivacaine did not change the basal activity of cardiac neurons in the dorsal horn or intermediolateral nucleus. After bupivacaine administration, the percentage of cardiac neurons that increased their activity in response to myocardial ischemia was decreased. Myocardial ischemia and cardiac load–dependent stress increased the short-term interactions between the dorsal horn and dorsal horn (324 to 931 correlated pairs out of 1,189 pairs, P < 0.0001), and dorsal horn and intermediolateral nucleus neurons (11 to 69 correlated pairs out of 1,135 pairs, P < 0.0001). Bupivacaine reduced this network response and augmentation in the interactions between dorsal horn–dorsal horn (931 to 38 correlated pairs out of 1,189 pairs, P < 0.0001) and intermediolateral nucleus–dorsal horn neurons (69 to 1 correlated pairs out of 1,135 pairs, P < 0.0001). Spinal bupivacaine reduced shortening of ventricular activation recovery interval and dispersion of repolarization, with decreased ventricular arrhythmogenesis during acute ischemia. Conclusions Spinal anesthesia reduces network interactions between dorsal horn–dorsal horn and dorsal horn–intermediolateral nucleus cardiac neurons in the spinal cord during myocardial ischemia. Blocking short-term coordination between local afferent–efferent cardiac neurons in the spinal cord contributes to a decrease in cardiac sympathoexcitation and reduction of ventricular arrhythmogenesis. Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New


2021 ◽  
Vol 4 ◽  
pp. 125-134
Author(s):  
Gary Tse ◽  
Guoliang Hao ◽  
Sharen Lee ◽  
Jiandong Zhou ◽  
Qingpeng Zhang ◽  
...  

2020 ◽  
Vol 4 (Issue 3) ◽  
Author(s):  
Osman Can Yontar

Objective: Ventricular arrhythmia episodes are not infrequent in patients with atrial septal defect (ASD). Disturbance in cardiac volume and pressures may lead to enlargement and fibrosis in heart. An interatrial volume displacement through septal defect, briefly interatrial shunt, is the major reason for this complication. Prolongation of the interval between the peak and end of the T wave (Tpeak to Tend, Tp-e) on the 12-lead electrocardiogram (ECG), is utilized as a marker of ventricular arrhythmogenesis during last years. The aim of this study was to assess if there is an impact of shunt ratio on ventricular repolarization in patients with ASD by using Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. Methods: Patient records of Samsun Training and Research Hospital were retrospectively analyzed. Electrocardiograms of 133 patients, who were diagnosed as ASD between January 2016 and December 2019 were obtained and scanned. ECG intervals were measured. Shunt ratios, right ventricle diameters and volumes were also acquired. Patients were grouped into two by their calculated shunt ratio, ratio of ≥2.0 is accepted as a high shunt group and <2.0 as a low shunt group. Results: Both groups’ baseline characteristics were similar. Right ventricular dimensions and systolic pulmonary artery pressure were higher in high shunt group. Furthermore, ASD patients with higher shunt ratio had significantly higher ECG measurements than controls, Tp-e: 103.0 (22.1) vs 76.2 (10.2); Tp-e/QT: 0.25 (0.03) vs 0.21 (0.02); Tp-e/QTc: 0.22 (0.03)  vs, 0.17 (0.02); for all p<0.001). Of all ECG parameters; Tp-e (r=0.631, p<0.001), Tp-e/QT (r=0.531, p<0.001) and Tp-e/QTc (r=0.614, p<0.001) had moderate correlation with shunt ratio. Conclusion: T wave peak-to-end interval is a measure of transmural dispersion of repolarization and accepted as a surrogate for increased ventricular arrhythmogenesis risk. Our findings show that ASD patients whose shunt ratio are ≥2.0 show increased risk for arrhythmias. Key words: atrial septal defect, electrocardiogram, ventricular arrhythmia, risk, ventricular repolarization


Sign in / Sign up

Export Citation Format

Share Document