scholarly journals NS5806 Induces Electromechanically Discordant Alternans and Arrhythmogenic Voltage-Calcium Dynamics in the Isolated Intact Rabbit Heart

2019 ◽  
Vol 10 ◽  
Author(s):  
Sufen Wang ◽  
Moisés Rodríguez-Mañero ◽  
Sergio H. Ibarra-Cortez ◽  
Bahij Kreidieh ◽  
Laura Valderrábano ◽  
...  
Keyword(s):  
Rabbit Heart ◽  
Calcium Dynamics ◽  
Intact Rabbit

Effect of Cold on the Isolated and Intact Rabbit Heart

1958 ◽  
Vol 13 (3) ◽  
pp. 422-424 ◽  
Author(s):  
Benjamin G. Covino ◽  
W. R. Beavers
Keyword(s):  
Rabbit Heart ◽  
Intact Rabbit

Electrophysiologic evaluation of cardiovascular agents in the isolated intact rabbit heart

1991 ◽  
Vol 25 (3) ◽  
pp. 205-213 ◽  
Author(s):  
Scott M. Balderston ◽  
Kenneth E. Johnson ◽  
Michael J. Reiter
Keyword(s):  
Rabbit Heart ◽  
Cardiovascular Agents ◽  
Intact Rabbit

scholarly journals Role of Reduced Sarco-Endoplasmic Reticulum Ca2+-ATPase Function on Sarcoplasmic Reticulum Ca2+ Alternans in the Intact Rabbit Heart

2021 ◽  
Vol 12 ◽  
Author(s):  
Lianguo Wang ◽  
Rachel C. Myles ◽  
I-Ju Lee ◽  
Donald M. Bers ◽  
Crystal M. Ripplinger
Keyword(s):  
Endoplasmic Reticulum ◽  
Sarcoplasmic Reticulum ◽  
Optical Mapping ◽  
Cyclopiazonic Acid ◽  
Rabbit Heart ◽  
Intracellular Ca ◽  
Cardiac Alternans ◽  
Intact Rabbit ◽  
Rapid Ventricular Pacing ◽  
Serca Inhibition

Sarcoplasmic reticulum (SR) Ca2+ cycling is tightly regulated by ryanodine receptor (RyR) Ca2+ release and sarco-endoplasmic reticulum Ca2+-ATPase (SERCA) Ca2+ uptake during each excitation–contraction coupling cycle. We previously showed that RyR refractoriness plays a key role in the onset of SR Ca2+ alternans in the intact rabbit heart, which contributes to arrhythmogenic action potential duration (APD) alternans. Recent studies have also implicated impaired SERCA function, a key feature of heart failure, in cardiac alternans and arrhythmias. However, the relationship between reduced SERCA function and SR Ca2+ alternans is not well understood. Simultaneous optical mapping of transmembrane potential (Vm) and SR Ca2+ was performed in isolated rabbit hearts (n = 10) using the voltage-sensitive dye RH237 and the low-affinity Ca2+ indicator Fluo-5N-AM. Alternans was induced by rapid ventricular pacing. SERCA was inhibited with cyclopiazonic acid (CPA; 1–10 μM). SERCA inhibition (1, 5, and 10 μM of CPA) resulted in dose-dependent slowing of SR Ca2+ reuptake, with the time constant (tau) increasing from 70.8 ± 3.5 ms at baseline to 85.5 ± 6.6, 129.9 ± 20.7, and 271.3 ± 37.6 ms, respectively (p < 0.05 vs. baseline for all doses). At fast pacing frequencies, CPA significantly increased the magnitude of SR Ca2+ and APD alternans, most strongly at 10 μM (pacing cycle length = 220 ms: SR Ca2+ alternans magnitude: 57.1 ± 4.7 vs. 13.4 ± 8.9 AU; APD alternans magnitude 3.8 ± 1.9 vs. 0.2 ± 0.19 AU; p < 0.05 10 μM of CPA vs. baseline for both). SERCA inhibition also promoted the emergence of spatially discordant alternans. Notably, at all CPA doses, alternation of SR Ca2+ release occurred prior to alternation of diastolic SR Ca2+ load as pacing frequency increased. Simultaneous optical mapping of SR Ca2+ and Vm in the intact rabbit heart revealed that SERCA inhibition exacerbates pacing-induced SR Ca2+ and APD alternans magnitude, particularly at fast pacing frequencies. Importantly, SR Ca2+ release alternans always occurred before the onset of SR Ca2+ load alternans. These findings suggest that even in settings of diminished SERCA function, relative refractoriness of RyR Ca2+ release governs the onset of intracellular Ca2+ alternans.

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