Effects of azumolene on arrhythmia substrate in a model of recurrent long-duration ventricular fibrillation

Chakraborty, Praloy; Massé, Stéphane; Azam, Muhammad; Thollon, Catherine; Niri, Ahmed; Lai, Patrick F.H.; Bouly, Muriel; Riazi, Sheila; Nanthakumar, Kumaraswamy

doi:10.1016/j.bbrc.2022.02.031

Cited by 3 publications

(1 citation statement)

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“… 24 Like APD‐ALT, APA‐ALT is also linked to ventricular arrhythmogenesis. 39 APA‐ALT is reported to follow more severe APD‐ALT, and the magnitude of APA‐ALT is known to correlate with ventricular fibrillation inducibility. 39 , 40 …”

Section: Discussionmentioning

confidence: 99%

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Zhao,

Du,

Chakraborty

et al. 2024

JAHA

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Background We recently demonstrated that acute administration of ibrutinib, a Bruton's tyrosine kinase inhibitor used in chemotherapy for blood malignancies, increases ventricular arrhythmia (VA) vulnerability. A pathway of ibrutinib‐induced vulnerability to VA that can be modulated for cardioprotection remains unclear. Methods and Results The effects of ibrutinib on cardiac electrical activity and Ca 2+ dynamics were investigated in Langendorff‐perfused hearts using optical mapping. We also conducted Western blotting analysis to evaluate the impact of ibrutinib on various regulatory and Ca 2+ ‐handling proteins in rat cardiac tissues. Treatment with ibrutinib (10 mg/kg per day) for 4 weeks was associated with an increased VA inducibility (72.2%±6.3% versus 38.9±7.0% in controls, P <0.002) and shorter action potential durations during pacing at various frequencies ( P <0.05). Ibrutinib also decreased heart rate thresholds for beat–to–beat duration alternans of the cardiac action potential ( P <0.05). Significant changes in myocardial Ca 2+ transients included lower amplitude alternans ratios ( P <0.05), longer times‐to‐peak ( P <0.05), and greater spontaneous intracellular Ca 2+ elevations ( P <0.01). We also found lower abundance and phosphorylation of myocardial AMPK (5′‐adenosine monophosphate‐activated protein kinase), indicating reduced AMPK activity in hearts after ibrutinib treatment. An acute treatment with the AMPK activator 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside ameliorated abnormalities in action potential and Ca 2+ dynamics, and significantly reduced VA inducibility (37.1%±13.4% versus 72.2%±6.3% in the absence of 5‐aminoimidazole‐4‐carboxamide‐1‐β‐D‐ribofuranoside, P <0.05) in hearts from ibrutinib‐treated rats. Conclusions VA vulnerability inflicted by ibrutinib may be mediated in part by an impairment of myocardial AMPK activity. Pharmacological activation of AMPK may be a protective strategy against ibrutinib‐induced cardiotoxicity.

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Section: Discussionmentioning

confidence: 99%

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Zhao,

Du,

Chakraborty

et al. 2024

JAHA

Self Cite

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Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia

Chakraborty,

Aggarwal,

Nair

et al. 2023

Heart Rhythm

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Acute effects of dantrolene on the mechanical performance of myopathic human hearts

Chakraborty,

Bokhari,

Massé

et al. 2024

Heart Rhythm

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Effects of azumolene on arrhythmia substrate in a model of recurrent long-duration ventricular fibrillation

Cited by 3 publications

References 42 publications

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia

Acute effects of dantrolene on the mechanical performance of myopathic human hearts

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Effects of azumolene on arrhythmia substrate in a model of recurrent long-duration ventricular fibrillation

Cited by 3 publications

References 42 publications

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca 2+ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca 2+ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Restoration of calcium release synchrony: A novel target for heart failure and ventricular arrhythmia

Acute effects of dantrolene on the mechanical performance of myopathic human hearts

Contact Info

Product

Resources

About

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability

Impaired Cardiac AMPK (5′‐Adenosine Monophosphate‐Activated Protein Kinase) and Ca ²⁺ ‐Handling, and Action Potential Duration Heterogeneity in Ibrutinib‐Induced Ventricular Arrhythmia Vulnerability