Optical pacing of the adult rabbit heart.
Ontology highlight
ABSTRACT:
SUBMITTER: Jenkins MW
PROVIDER: S-EPMC3771833 | biostudies-other | 2013
REPOSITORIES: biostudies-other
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Project description:Light has been used to noninvasively alter the excitability of both neural and cardiac tissue 1-10. Recently, pulsed laser light has been shown to be capable of eliciting action potentials in peripheral nerves and in cultured cardiomyocytes 7-10. Here, we demonstrate for the first time optical pacing (OP) of an intact heart in vivo. Pulsed 1.875 ?m infrared laser light was employed to lock the heart rate to the pulse frequency of the laser. A laser Doppler velocimetry (LDV) signal was used to verify the pacing. At low radiant exposures, embryonic quail hearts were reliably paced in vivo without detectable damage to the tissue, indicating that OP has great potential as a tool to study embryonic cardiac dynamics and development. In particular, OP can be utilized to control the heart rate, and thereby alter stresses and mechanically transduced signaling.
| S-EPMC3059323 | biostudies-other
Project description:AimsMechanical stimulation (MS) represents a readily available, non-invasive means of pacing the asystolic or bradycardic heart in patients, but benefits of MS at higher heart rates are unclear. Our aim was to assess the maximum rate and sustainability of excitation by MS vs. electrical stimulation (ES) in the isolated heart under normal physiological conditions.Methods and resultsTrains of local MS or ES at rates exceeding intrinsic sinus rhythm (overdrive pacing; lowest pacing rates 2.5±0.5 Hz) were applied to the same mid-left ventricular free-wall site on the epicardium of Langendorff-perfused rabbit hearts. Stimulation rates were progressively increased, with a recovery period of normal sinus rhythm between each stimulation period. Trains of MS caused repeated focal ventricular excitation from the site of stimulation. The maximum rate at which MS achieved 1:1 capture was lower than during ES (4.2±0.2 vs. 5.9±0.2 Hz, respectively). At all overdrive pacing rates for which repetitive MS was possible, 1:1 capture was reversibly lost after a finite number of cycles, even though same-site capture by ES remained possible. The number of MS cycles until loss of capture decreased with rising stimulation rate. If interspersed with ES, the number of MS to failure of capture was lower than for MS only.ConclusionIn this study, we demonstrate that the maximum pacing rate at which MS can be sustained is lower than that for same-site ES in isolated heart, and that, in contrast to ES, the sustainability of successful 1:1 capture by MS is limited. The mechanism(s) of differences in MS vs. ES pacing ability, potentially important for emergency heart rhythm management, are currently unknown, thus warranting further investigation.
| S-EPMC5400084 | biostudies-literature
Project description:Dantrolene was reported to suppress ventricular fibrillation (VF) in failing hearts with acute myocardial infarction, but its antiarrhythmic efficacy in regional ischemia-reperfusion (IR) hearts remains debatable. Heart failure (HF) was induced by right ventricular pacing. The IR rabbit model was created by coronary artery ligation for 30 min, followed by reperfusion for 15 min in vivo in both HF and non-HF groups (n = 9 in each group). Simultaneous voltage and intracellular Ca(2+) (Cai) optical mapping was then performed in isolated Langendorff-perfused hearts. Electrophysiological studies were conducted and VF inducibility was evaluated by dynamic pacing. Dantrolene (10 μM) was administered after baseline studies. The HF group had a higher VF inducibility than the control group. Dantrolene had both antiarrhythmic (prolonged action potential duration (APD) and effective refractory period) and proarrhythmic effects (slowed conduction velocity, steepened APD restitution slope, and enhanced arrhythmogenic alternans induction) but had no significant effects on ventricular premature beat (VPB) suppression and VF inducibility in both groups. A higher VF conversion rate in the non-HF group was likely due to greater APD prolonging effects in smaller hearts compared to the HF group. The lack of significant effects on VPB suppression by dantrolene suggests that triggered activity might not be the dominant mechanism responsible for VPB induction in the IR model.
| S-EPMC4350948 | biostudies-literature
Project description:BackgroundBecause of the optical features of heart tissue, optical and electrical action potentials are only moderately associated, especially when near-infrared dyes are used in optical mapping (OM) studies.ObjectiveBy simultaneously recording transmural electrical action potentials (APs) and optical action potentials (OAPs), we aimed to evaluate the contributions of both electrical and optical influences to the shape of the OAP upstroke.Methods and resultsA standard glass microelectrode and OM, using an near-infrared fluorescent dye (di-4-ANBDQBS), were used to simultaneously record transmural APs and OAPs in a Langendorff-perfused rabbit heart during atrial, endocardial, and epicardial pacing. The actual profile of the transmural AP upstroke across the LV wall, together with the OAP upstroke, allowed for calculations of the probing-depth constant (k ~2.1 mm, n = 24) of the fluorescence measurements. In addition, the transmural AP recordings aided the quantitative evaluation of the influences of depth-weighted and lateral-scattering components on the OAP upstroke. These components correspond to the components of the propagating electrical wave that are transmural and parallel to the epicardium. The calculated mean values for the depth-weighted and lateral-scattering components, whose sum comprises the OAP upstroke, were (in ms) 10.18 ± 0.62 and 0.0 ± 0.56 for atrial stimulation, 9.37 ± 1.12 and 3.01 ± 1.30 for endocardial stimulation, and 6.09 ± 0.79 and 8.16 ± 0.98 for epicardial stimulation; (n = 8 for each). For this dye, 90% of the collected fluorescence originated up to 4.83 ± 0.18 mm (n = 24) from the epicardium.ConclusionsThe co-registration of OM and transmural microelectrode APs enabled the probing depth of fluorescence measurements to be calculated and the OAP upstroke to be divided into two components (depth-weighted and lateral-scattering), and it also allowed the relative strengths of their effects on the shape of the OAP upstroke to be evaluated.
| S-EPMC4400155 | biostudies-literature
Project description:Adult New Zealand White rabbits (2-2.5 kg) mRNA quantification.
2018-08-01 | GSE115605 | GEO
Project description:BackgroundLeft bundle branch pacing (LBBP) has emerged as an alternative to biventricular pacing (BVP) for delivering cardiac resynchronization therapy. We sought to compare the acute improvement of electrical and mechanical synchrony, and hemodynamics between LBBP and BVP in patients with heart failure and left bundle branch block.MethodsLBBP and BVP were performed and compared in a crossover fashion in patients with heart failure and left bundle branch block undergoing cardiac resynchronization therapy implantation. Electrical synchrony was assessed by QRS duration and area, mechanical synchrony by the SD of time to peak velocity of 12 left ventricular segments (Ts-SD) and interventricular mechanical delay, and hemodynamics by the maximum rate of left ventricular pressure rise (dP/dtmax).ResultsTwenty-one patient with heart failure and left bundle branch block (mean age 67±10 years, 48% male, and 90% nonischemic cause) were included. Both LBBP and BVP provided significant improvements in electrical and mechanical synchrony, and hemodynamics compared to the baseline. Compared with BVP, LBBP achieved a larger reduction in QRS duration (-11 ms [95% CI, -17 to -4 ms]; P=0.003) and QRS area (-85 µVs [95% CI, -113 to -56 µVs]; P<0.001); LBBP achieved a greater decrease in Ts-SD (-14 ms [95% CI, -21 to -7 ms]; P=0.001), with no significant difference in interventricular mechanical delay (-2 ms [95% CI, -13 to 8 ms]; P=0.63). The increase in dP/dtmax from LBBP was significantly higher than that from BVP (6% [95% CI, 2%-9%]; P=0.002).ConclusionsLBBP delivers greater acute electrical and mechanical resynchronization and hemodynamic improvement than BVP in predominantly nonischemic heart failure patients with left bundle branch block.RegistrationURL: https://www.Clinicaltrialsgov; Unique identifier: NCT04505384.
| S-EPMC9665950 | biostudies-literature
Project description:Tachycardia-induced atrial fibrosis is a hallmark of the structural remodeling of atrial fibrillation (AF). The mechanisms underlying tachycardia-induced atrial fibrosis remain unclear. In our previous study, we found that Smad7-downregulation promoted the development of atrial fibrosis in AF. Fibroblasts are enriched in microRNA-21 (miR-21), which contributes to the development of fibrosis and heart failure in the cardiovascular system. Our study was designed to test the hypothesis that miR-21 reinforces the TGF-β1/Smad signaling pathway in AF-induced atrial fibrosis by down-regulating Smad7. Rapid atrial pacing (RAP, 1000 ppm) was applied to the left atrium of the rabbit heart to induce atrial fibrillation and fibrosis. qRT-PCR and northern blot analysis revealed that RAP caused a marked increase in the expression of miR-21. Transfection with a miR-21 inhibitor significantly increased the expression of Smad7, while the expression of collagen I/III significantly decreased. These changes were implicated in the AF-induced release of miR-21 and down-regulation of Smad7. Adult rat cardiac fibroblasts treated with TGF-β1 showed increased miR-21 expression and decreased Smad7 expression. Pretreatment with a TGF-β1 inhibitor reduced the TGF-β1-induced up-regulation of miR-21. Pretreatment with pre-miR-21 and a miR-21 inhibitor significantly decreased and increased Smad7 expression, respectively. This result was negatively correlated with the expression of collagen I/III in fibroblasts. Moreover, the results of a luciferase activity assay suggest that Smad7 is a validated miR-21 target in CFs. Our results provide compelling evidence that the miR-21 specific degradation of Smad7 may decrease the inhibitory feedback regulation of TGF-β1/Smad signaling and serves as a new insight of the mechanism of atrial fibrosis in atrial fibrillation.
| S-EPMC5043001 | biostudies-literature
Project description:AimsLeft bundle branch area pacing (LBBAP) has been shown to be effective and safe. Limited data are available on LBBAP in the congenital heart disease (CHD) population. This study aims to describe the feasibility and safety of LBBAP in CHD patients compared with non-CHD patients.Methods and resultsThis is a single-centre, non-randomized observational study recruiting consecutive patients with bradycardia indication. Demographic data, ECGs, imaging, and procedural data including lead parameters were recorded. A total of 39 patients were included: CHD group (n = 13) and non-CHD group (n = 26). Congenital heart disease patients were younger (55 ± 14.5 years vs. 73.2 ± 13.1, P < 0.001). Acute success was achieved in all CHD patients and 96% (25/26) of non-CHD patients. No complications were encountered in either group. The procedural time for CHD patients was comparable (96.4 ± 54 vs. 82.1 ± 37.9 min, P = 0.356). Sheath reshaping was required in 7 of 13 CHD patients but only in 1 of 26 non-CHD patients, reflecting the complex and distorted anatomy of the patients in this group. Lead parameters were similar in both groups; R wave (11 ± 7 mV vs. 11.5 ± 7.5, P = 0.881) and pacing threshold (0.6 ± 0.3 V vs. 0.7 ± 0.3, P = 0.392). Baseline QRS duration was longer in the CHD group (150 ± 28.2 vs. 118.6 ± 26.6 ms, P = 0.002). Despite a numerically greater reduction in QRS and a similar left ventricular activation time (65.9 ± 6.2 vs. 67 ± 16.8 ms, P = 0.840), the QRS remained longer in the CHD group (135.5 ± 22.4 vs. 106.9 ± 24.7 ms, P = 0.005).ConclusionLeft bundle branch area pacing is feasible and safe in CHD patients as compared to that in non-CHD patients. Procedural and fluoroscopy times did not differ between both groups. Lead parameters were satisfactory and stable over a short-term follow-up.
| S-EPMC9935007 | biostudies-literature
Project description:Optogenetic methods for pacing of cardiac tissue can be realized by direct genetic modification of the cardiomyocytes to express light-sensitive actuators, such as channelrhodopsin-2, ChR2, or by introduction of light-sensitized non-myocytes that couple to the cardiac cells and yield responsiveness to optical pacing. In this study, we engineer three-dimensional "spark cells" spheroids, composed of ChR2-expressing human embryonic kidney cells (from 100 to 100,000 cells per spheroid), and characterize their morphology as function of cell density and time. These "spark-cell" spheroids are then deployed to demonstrate site-specific optical pacing of human stem-cell-derived cardiomyocytes (hiPSC-CMs) in 96-well format using non-localized light application and all-optical electrophysiology with voltage and calcium small-molecule dyes or genetically encoded sensors. We show that the spheroids can be handled using liquid pipetting and can confer optical responsiveness of cardiac tissue earlier than direct viral or liposomal genetic modification of the cardiomyocytes, with 24% providing reliable stimulation of the iPSC-CMs within 6 h and >80% within 24 h. Moreover, our data show that the spheroids can be frozen in liquid nitrogen for long-term storage and transportation, after which they can be deployed as a reagent on site for optical cardiac pacing. In all cases, optical stimulation was achieved at relatively low light levels (<0.15 mW/mm2) when 5 ms or longer pulses were used. Our results demonstrate a scalable, cost-effective method with a cryopreservable reagent to achieve contactless optical stimulation of cardiac cell constructs without genetically modifying the myocytes, that can be integrated in a robotics-amenable workflow for high-throughput drug testing.
| S-EPMC8249938 | biostudies-literature
Project description:Human cardiac myocytes derived from pluripotent stem cells (hCM) have invigorated interest in genetic disease mechanisms and cardiac safety testing; however, the technology to fully assess electrophysiological function in an assay that is amenable to high throughput screening has lagged. We describe a fully contactless system using optical pacing with an infrared (IR) laser and multi-site high fidelity fluorescence imaging to assess multiple electrophysiological parameters from hCM monolayers in a standard 96-well plate. Simultaneous multi-site action potentials (FluoVolt) or Ca2+ transients (Fluo4-AM) were measured, from which high resolution maps of conduction velocity and action potential duration (APD) were obtained in a single well. Energy thresholds for optical pacing were determined for cell plating density, laser spot size, pulse width, and wavelength and found to be within ranges reported previously for reliable pacing. Action potentials measured using FluoVolt and a microelectrode exhibited the same morphology and rate of depolarization. Importantly, we show that this can be achieved accurately with minimal damage to hCM due to optical pacing or fluorescence excitation. Finally, using this assay we demonstrate that hCM exhibit reproducible changes in repolarization and impulse conduction velocity for Flecainide and Quinidine, two well described reference compounds. In conclusion, we demonstrate a high fidelity electrophysiological screening assay that incorporates optical pacing with IR light to control beating rate of hCM monolayers.
| S-EPMC5570338 | biostudies-literature