scholarly journals Construction and use of a zebrafish heart voltage and calcium optical mapping system, with integrated electrocardiogram and programmable electrical stimulation

2015 ◽  
Vol 308 (9) ◽  
pp. R755-R768 ◽  
Author(s):  
Eric Lin ◽  
Calvin Craig ◽  
Marcel Lamothe ◽  
Marinko V. Sarunic ◽  
Mirza Faisal Beg ◽  
...  
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Large Scale ◽  
Optical Mapping ◽  
Rate Dependence ◽  
P Wave ◽  
Calcium Dynamics ◽  
Mapping System ◽  
Electrical Stimulator ◽  
Zebrafish Heart

Zebrafish are increasingly being used as a model of vertebrate cardiology due to mammalian-like cardiac properties in many respects. The size and fecundity of zebrafish make them suitable for large-scale genetic and pharmacological screening. In larger mammalian hearts, optical mapping is often used to investigate the interplay between voltage and calcium dynamics and to investigate their respective roles in arrhythmogenesis. This report outlines the construction of an optical mapping system for use with zebrafish hearts, using the voltage-sensitive dye RH 237 and the calcium indicator dye Rhod-2 using two industrial-level CCD cameras. With the use of economical cameras and a common 532-nm diode laser for excitation, the rate dependence of voltage and calcium dynamics within the atrial and ventricular compartments can be simultaneously determined. At 140 beats/min, the atrial action potential duration was 36 ms and the transient duration was 53 ms. With the use of a programmable electrical stimulator, a shallow rate dependence of 3 and 4 ms per 100 beats/min was observed, respectively. In the ventricle the action potential duration was 109 ms and the transient duration was 124 ms, with a steeper rate dependence of 12 and 16 ms per 100 beats/min. Synchronous electrocardiograms and optical mapping recordings were recorded, in which the P-wave aligns with the atrial voltage peak and R-wave aligns with the ventricular peak. A simple optical pathway and imaging chamber are detailed along with schematics for the in-house construction of the electrocardiogram amplifier and electrical stimulator. Laboratory procedures necessary for zebrafish heart isolation, cannulation, and loading are also presented.

Reverse use dependence of calcium sensitizer levosimendan on action potential duration shortening prevents ventricular arrhythmia during therapeutic hypothermia

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
Y.C Hsieh ◽  
C.H Li ◽  
J.C Lin ◽  
C.J Weng ◽  
Y.S Chien ◽  
...  
Keyword(s):  
Ventricular Arrhythmia ◽  
Action Potential ◽  
Therapeutic Hypothermia ◽  
Action Potential Duration ◽  
Heart Failure Treatment ◽  
Novel Approach ◽  
Mapping System ◽  
Diastolic Interval ◽  
K Current ◽  
Calcium Sensitizer

Abstract Background Therapeutic hypothermia (TH) increases the risk of ventricular arrhythmia (VA) by prolonging action potential duration (APD) and steepening the APD restitution (APDR). The calcium sensitizer levosimendan, a medication for heart failure treatment, has been reported to shorten APD by enhancing ATP-sensitive K current and affect the APDR. Purpose We hypothesized that levosimendan might shorten the already prolonged APD particularly at long pacing cycle length (PCL), thus decreases the maximal slope of APDR, and prevent VA during TH. Methods Langendorff-perfused isolated rabbit hearts were subjected to 15-min TH (30°C) followed by 30-min treatment with levosimendan (0.5 μM, n=9) or vehicle (n=8). Using an optical mapping system, APD was evaluated by S1 pacing and APDR curve was plotted using APD70 versus diastolic interval. Ventricular fibrillation (VF) inducibility was evaluated by burst pacing for 30 s at the shortest PCL that achieved 1:1 ventricular capture. Results The APD was shortened from 259±8 ms at TH to 241±18 ms after levosimendan infusion at long PCL of 400 ms (p=0.024). However, at short PCL of 280 ms, the APD was not changed before (194±19) and after (188±23) levosimendan during TH (p=0.61). Levosimendan decreases the maximal slope of APDR curve from 1.99±0.65 at TH to 1.41±0.32 after adding levosimendan (p=0.034). The VF inducibility was decreased by levosimendan from 39±30% at 30°C to 14±12% with levosimendan (p=0.023). In control hearts, the maximal slope of APDR (p=0.75) and VF inducibility (p=0.12) were not changed by vehicle during TH. Conclusion Levosimendan might protect the hearts against VA during TH by shortening APD at long PCL and flattening the APDR. Enhancing ATP-sensitive K current with levosimendan during TH might be a novel approach to prevent VA during TH. Funding Acknowledgement Type of funding source: None

scholarly journals Optical mapping of the electrical activity of isolated adult zebrafish hearts: acute effects of temperature

2014 ◽  
Vol 306 (11) ◽  
pp. R823-R836 ◽  
Author(s):  
Eric Lin ◽  
Amanda Ribeiro ◽  
Weiguang Ding ◽  
Leif Hove-Madsen ◽  
Marinko V. Sarunic ◽  
...  
Keyword(s):  
Action Potential ◽  
Electrical Activity ◽  
Cardiac Electrophysiology ◽  
Optical Mapping ◽  
Cooling System ◽  
Effect Of Temperature ◽  
Adult Zebrafish ◽  
Depth Analysis ◽  
Zebrafish Heart ◽  
Av Delay

The zebrafish ( Danio rerio) has emerged as an important model for developmental cardiovascular (CV) biology; however, little is known about the cardiac function of the adult zebrafish enabling it to be used as a model of teleost CV biology. Here, we describe electrophysiological parameters, such as heart rate (HR), action potential duration (APD), and atrioventricular (AV) delay, in the zebrafish heart over a range of physiological temperatures (18–28°C). Hearts were isolated and incubated in a potentiometric dye, RH-237, enabling electrical activity assessment in several distinct regions of the heart simultaneously. Integration of a rapid thermoelectric cooling system facilitated the investigation of acute changes in temperature on critical electrophysiological parameters in the zebrafish heart. While intrinsic HR varied considerably between fish, the ex vivo preparation exhibited impressively stable HRs and sinus rhythm for more than 5 h, with a mean HR of 158 ± 9 bpm (means ± SE; n = 20) at 28°C. Atrial and ventricular APDs at 50% repolarization (APD50) were 33 ± 1 ms and 98 ± 2 ms, respectively. Excitation originated in the atrium, and there was an AV delay of 61 ± 3 ms prior to activation of the ventricle at 28°C. APD and AV delay varied between hearts beating at unique HRs; however, APD and AV delay did not appear to be statistically dependent on intrinsic basal HR, likely due to the innate beat-to-beat variability within each heart. As hearts were cooled to 18°C (by 1°C increments), HR decreased by ∼40%, and atrial and ventricular APD50 increased by a factor of ∼3 and 2, respectively. The increase in APD with cooling was disproportionate at different levels of repolarization, indicating unique temperature sensitivities for ion currents at different phases of the action potential. The effect of temperature was more apparent at lower levels of repolarization and, as a whole, the atrial APD was the cardiac parameter most affected by acute temperature change. In conclusion, this study describes a preparation enabling the in-depth analysis of transmembrane potential dynamics in whole zebrafish hearts. Because the zebrafish offers some critical advantages over the murine model for cardiac electrophysiology, optical mapping studies utilizing zebrafish offer insightful information into the understanding and treatment of human cardiac arrhythmias, as well as serving as a model for other teleosts.

scholarly journals P478Cardiac response to live music performance: effect of large-scale musical structure on action potential duration

EP Europace ◽  
2020 ◽  
Vol 22 (Supplement_1) ◽  
Author(s):  
E Chew ◽  
P Taggart ◽  
P Lambiase
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Large Scale ◽  
Electrical Response ◽  
Music Performance ◽  
Intracardiac Electrogram ◽  
Live Music ◽  
Before And After ◽  
The Impact ◽  
Live Music Performance

Abstract Funding Acknowledgements This work has received funding from the ERC under the EU’s Horizon 2020 R&I programme (Grant agreement No. 788960) Background Strong emotions can trigger cardiac arrhythmias, but the heart-brain mechanism by which they do so is not well understood. Music induces strong emotions, precipitated by musical changes and intensified during live performance; it thus serves as a powerful tool through which to investigate heart-brain interaction. However, existing studies use short, artificial or pre-recorded music excerpts, out of context and classified into singular, simple emotion classes over which aggregate response are reported, ignoring the range of responses possible for the same music stimulus. None has considered electrical response to music as measured from the heart muscles.  Purpose To evaluate the impact on action potential duration due to musical changes at large-scale structural boundaries in live music performance.  Methods Patients implanted with biventricular pacemakers/ICDs are invited to a live classical piano concert. Prior to the concert, the patients’ pacemakers are programmed from CRT to dual chamber pacing at 80 bpm or ten above their intrinsic heart rate. Following a ten-minute adjustment period, they listen to three pieces lasting 15 minutes; this was subsequently expanded to five lasting 30 minutes. Continuous recordings of the intracardiac electrogram (EGM) signals are downloaded from the ICD lead connected to the left ventricle whilst the patients listen to the music. The pacemakers are returned to their original settings after the concert. The patients further provide annotations for perceived change boundaries and tension, as well as information on their music training/experience. We approximate the action potential duration (APD) using the action recovery interval (ARI) extracted from the EGM signal, and compare the ARIs before and after each structural boundary indicated in the music score.  Results We analyze the ARI data surrounding 24 music structural boundaries. The first results are for the three patients (two male; one female) from the initial study day. We perform a two-sample t-test to assess the population means in ARI values before and after each of the 24 structural boundaries. The figure attached shows the statistically significant changes across structural boundaries for α = 0.05; the bar plots show the sample means and 95% confidence intervals (CI) for the 80 ARIs before and after a boundary, and report the p-values of the t-tests. Patients 1 and 3 each reacted significantly to three out of the 24 boundaries (12.5%), sometimes in opposite directions, and Patient 2 to 15 out of the 24 boundaries (62.5%). The CIs for the significant differences spanned the range (–4.4896,4.8745).  Conclusions We show that structural boundaries, where music features change or transition, can produce significant changes in APD. A range of significant responses are observed, including contradictory ones, that span a nearly 10ms range, which could play a contributory role to clinical understanding of arrhythmias and emotion responses. Abstract Figure.

scholarly journals Ventricular gradient and nondipolar repolarization components increase at higher heart rate

2004 ◽  
Vol 286 (1) ◽  
pp. H131-H136 ◽  
Author(s):  
Peter Smetana ◽  
Velislav N. Batchvarov ◽  
Katerina Hnatkova ◽  
A. John Camm ◽  
Marek Malik
Keyword(s):  
Heart Rate ◽  
Action Potential ◽  
Action Potential Duration ◽  
Rate Dependence ◽  
Rr Intervals ◽  
Heart Rates ◽  
Qt Intervals ◽  
Ion Channel Properties ◽  
Transmural Dispersion ◽  
Relationship Of

Differences in action potential duration reflect differences in ion channel properties. These properties also determine rate dependence of action potential duration, and transmural dispersion was confirmed experimentally to increase with cycle length. While several electrocardiographic indexes characterizing repolarization abnormalities have been proposed, studies of their heart rate dependence are missing. This study therefore investigated rate relationship of two repolarization descriptors, namely, the so-called total cosine of the QRS-T angle (TCRT), proposed to characterize global repolarization heterogeneity, and the so-called relative T wave residuum (TWR), linked to regional repolarization dispersion. During 24-h holter recordings in 60 healthy subjects (27 males), a 12-lead ECG was obtained every 30 s. RR intervals, QT intervals, and TCRT and TWR were calculated in each ECG and averaged over RR interval bins ranging from 550 to 1,150 ms in 10-ms steps. Women had uniformly greater TCRT and TWR values than men did over the entire range of investigated RR intervals. Whereas the TCRT in both sexes showed marked rate dependence with higher values at long RR intervals (550 vs. 1,150 ms: women, 0.46 ± 0.31 vs. 0.76 ± 0.18, P = 9 × 10–7; men, 0.08 ± 0.45 vs. 0.49 ± 0.35, P = 9 × 10–8), the rate dependence of TWR was more marked in women than in men, showing higher values at shorter RR intervals (550 ms vs. 1,150 ms: women: 0.29 ± 0.14% vs. 0.08 ± 0.06%, P = 2 × 10–8; men: 0.14 ± 0.12% vs. 0.04 ± 0.02%, P = 2 × 10–15). This suggests that both global and regional repolarization heterogeneity are increased at faster heart rates. Whereas in women at all heart rates the sequence of repolarization more closely replicates the sequence of depolarization, localized repolarization is more heterogeneous than in men especially at fast heart rates.

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