scholarly journals Real-Time Closed-Loop Suppression of Repolarization Alternans Reduces Arrhythmia Susceptibility In Vivo

2020 ◽  
Vol 13 (6) ◽  
Author(s):  
Faisal M. Merchant ◽  
Omid Sayadi ◽  
Kwanghyun Sohn ◽  
Eric H. Weiss ◽  
Dheeraj Puppala ◽  
...  

Background: Repolarization alternans (RA) has been implicated in the pathogenesis of ventricular arrhythmias and sudden cardiac death. Methods: We have developed a real-time, closed-loop system to record and analyze RA from multiple intracardiac leads, and deliver dynamically R-wave triggered pacing stimuli during the absolute refractory period. We have evaluated the ability of this system to control RA and reduce arrhythmia susceptibility, in vivo. Results: R-wave triggered pacing can induce RA, the magnitude of which can be modulated by varying the amplitude, pulse width, and size of the pacing vector. Using a swine model (n=9), we demonstrate that to induce a 1 µV change in the alternans voltage on the body surface, coronary sinus and left ventricle leads, requires a delivered charge of 0.04±0.02, 0.05±0.025, and 0.06±0.033 µC, respectively, while to induce a one unit change of the K score , requires a delivered charge of 0.93±0.73, 0.32±0.29, and 0.33±0.37 µC, respectively. For all body surface and intracardiac leads, both Δ(alternans voltage) and ΔK score between baseline and R-wave triggered paced beats increases consistently with an increase in the pacing pulse amplitude, pulse width, and vector spacing. Additionally, we show that the proposed method can be used to suppress spontaneously occurring alternans (n=7), in the presence of myocardial ischemia. Suppression of RA by pacing during the absolute refractory period results in a significant reduction in arrhythmia susceptibility, evidenced by a lower S rank score during programmed ventricular stimulation compared with baseline before ischemia. Conclusions: We have developed and evaluated a novel closed-loop method to dynamically modulate RA in a swine model. Our data suggest that suppression of RA directly reduces arrhythmia susceptibility and reinforces the concept that RA plays a critical role in the pathophysiology of arrhythmogenesis.

Author(s):  
Yehong Fang ◽  
Shu Han ◽  
Xiaoxue Li ◽  
Yikuan Xie ◽  
Bing Zhu ◽  
...  

Abstract Pain on the body surface can accompany disorders in the deep tissue or internal organs. However, the anatomical and physiological mechanisms are obscure. Here, we provided direct evidence of axon bifurcation in primary C-nociceptive neurons that innervate both the skin and a visceral organ. Double-labeled dorsal root ganglion (DRG) neurons and Evans blue extravasation were observed in 3 types of chemically-induced visceral inflammation (colitis, urocystitis, and acute gastritis) rat models. In the colitis model, mechanical hypersensitivity and spontaneous activity were recorded in vivo from double-labeled C-nociceptive neurons in S1 or L6 DRGs. These neurons showed significantly enhanced responses to both somatic stimulation and colorectal distension. Our findings suggest that the branching of C-nociceptor axons contribute to cutaneous hypersensitivity in visceral inflammation. Cutaneous hypersensitivity on certain locations of the body surface might serve as an indicator of pathological conditions in the corresponding visceral organ.


2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
K Garrott ◽  
A Sugrue ◽  
J Laughner ◽  
J Bush ◽  
S Gutbrod ◽  
...  

Abstract Catheter-tissue coupling is crucial for effective delivery of radiofrequency (RF) energy during catheter ablation. Force sensing catheters provide a metric of mechanical tissue contact and catheter stability, while local impedance has been shown to provide sensitive information on real-time tissue heating. The complementary use of force and local impedance during RF ablation procedures could provide an advantage over the use of one metric alone. This study evaluates a prototype ablation catheter that measures both contact force (CF) using inductive sensors and local catheter impedance (LI) using only catheter electrodes. The complementary nature was assessed with discrete lesions in vitro and an intercaval line in vivo. A force-sensing catheter with LI was evaluated in explanted swine hearts (n=14) in an in vivo swine model (n=9, 50–70kg) using investigational electroanatomical mapping software. In vitro, discrete lesions were created in ventricular tissue at a range of forces (0–40g) controlled externally. RF energy was applied at a range of powers (20W, 30W, and 40W), durations (10s-60s), and catheter orientations (0°, 45°, and 90°). Lesions were stained with TTC and measured. LI drop relative to baseline during RF in the bench studies was used to inform the in vivo study. In a separate subset of animals in vivo, an intercaval line was created in three experimental groups: LI blinded, 20Ω ΔLI, and 30Ω ΔLI. CF was maintained between 15 and 25g in all groups. All ablations were performed with a power of 30W. In the LI blinded group, all lesions were delivered for 30s. In the 20Ω ΔLI group, the investigator ablated until a 20Ω drop or 30 seconds was achieved. Likewise, in the 30Ω ΔLI, the investigator ablated until a 30Ω drop or 30 seconds was achieved. In vitro, 137 discrete ventricular lesions were created. LI drop during ablation correlated strongly with lesion depth using a monoexponential fit (R=0.84) while force time integral (FTI) did not correlate as strongly (R=0.56). In the intercaval LI blinded group, starting LI ranged from 126–163Ω with a median of 138Ω. LI drops ranged from 13Ω-44Ω, with a median of 26Ω. In the 20Ω ΔLI group, starting LI ranged from 137–211Ω with a median of 161Ω and LI drop ranged from 7Ω-35Ω, with a median of 22Ω. In the 30Ω ΔLI group, starting LI ranged from 130–256Ω with a median of 171Ω and LI drop ranged from 20Ω-52Ω, with a median of 31Ω. Notably, RF time for the LI blinded group was 13±0.1 minutes while RF time in the 20Ω ΔLI group was 6.4±1.9 minutes and 7.5±0.7 minutes in the 30Ω ΔLI group. A catheter incorporating CF-sensing and LI capabilities provides a powerful tool for RF ablation. Bench studies demonstrate a strong correlation between LI drop and lesion dimensions, which guided the use of LI in vivo. In vivo, the confirmation of stable mechanical contact and viewing of real-time LI drops enabled a significant reduction in RF time while creating a continuous intercaval line. Acknowledgement/Funding This study was funded by Boston Scientific.


1960 ◽  
Vol 44 (2) ◽  
pp. 415-432 ◽  
Author(s):  
A. J. Brady ◽  
B. C. Abbott ◽  
W. F. H. M. Mommaerts

The application of a train of supramaximal stimuli during the absolute refractory period of a cardiac muscle preparation has two effects: a depression of the contraction during which it is applied, and a large potentiation of subsequent contractions. The former is ascribed to a direct effect upon the cell membrane, and is an indication of the continued control of the contractile event by this membrane. The latter is explained as a sudden liberation of norepinephrine by a stimulation of embedded nerve elements, which norepinephrine then distributes itself through the tissue and finally diffuses away.


2019 ◽  
Vol 66 (11) ◽  
pp. 3212-3219
Author(s):  
Viksit Kumar ◽  
Minako Katayama ◽  
Rachael Peavler ◽  
Azra Alizad ◽  
Marek Belohlavek ◽  
...  

1966 ◽  
Vol 14 (4) ◽  
pp. 280-289
Author(s):  
W.T. Binnerts

Cows were inoculated i/v and i/m with Cu-64 and the radioactivity of the liver was measured in vivo and P.M. The absolute and relative errors of the in vivo measurements were calculated. Studies also included the geometry of the body related to the counting system, and the position of the counter, its shielding and the value of background readings. (Abstract retrieved from CAB Abstracts by CABI’s permission)


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