Effects of Antiarrhythmics on Cardiac Phenotype and Redox Balance in Spontaneously Hypertensive Rats

Q: What is the clinical evidence from this study?

Population: Arterial hypertension (n=24). Intervention: Class III antiarrhythmic drugs (dronedarone, amiodarone, dofetilide) vs. Saline (untreated SHR group).

Q: What does this research mean for the field?

Class III antiarrhythmic drugs (dronedarone, amiodarone, and dofetilide) differentially modulate cardiac function, redox balance, calcium handling, and myocardial remodeling in hypertensive rats. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Stefan Simović; Ivan Srejović; Goran T. Davidović; M Nikolić; Slobodanka L. Mitrović; Marko Ravic; Marijana Andjić; Marina Nikolić; Katarina G. Mihajlović; Nevena Draginić; Sergey B. Bolevich; Aleksandra S. Orlova; Marina A. Fokina; Sergey E. Mironov; Vladimir Jakovljević; Jovana Novaković

doi:10.3390/ijms27146490

July 21, 2026International Journal of Molecular SciencesOpen Access

Effects of Antiarrhythmics on Cardiac Phenotype and Redox Balance in Spontaneously Hypertensive Rats

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Key result

Dofetilide best preserves myocardial architecture among class III antiarrhythmics in hypertensive rat models.

n=24

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Why the study?

Arterial hypertension is a risk factor for cardiac arrhythmias, and certain antihypertensive agents may create conditions for arrhythmia occurrence, prompting evaluation of selected class III antiarrhythmic drugs in hypertension.

Do class III antiarrhythmic drugs (dronedarone, amiodarone, dofetilide) improve cardiac function, redox balance, and myocardial remodeling in spontaneously hypertensive rats?

Key Points

To evaluate the effects of selected class III antiarrhythmic drugs on cardiac function, myocardial morphology, and oxidative stress status in spontaneously hypertensive rats.
Treated male spontaneously hypertensive rats for 4 weeks with dronedarone, amiodarone, or dofetilide.
Assessed cardiac function in vivo via transthoracic echocardiography and ex vivo using an isolated retrograde Langendorff perfusion model across coronary perfusion pressures of 40–120 cmH 2 O.
Quantified systemic and coronary oxidative stress parameters, examined histological myocardial morphology, and measured HSP70 and SERCA2 protein expression by immunohistochemistry.
At baseline, blood pressure was elevated in all groups (SHR: 173 ± 8/104 ± 4; Dron: 171 ± 6/102 ± 5; Ami: 174 ± 7/101 ± 5; Dof: 174 ± 4/102 ± 6); after 4 weeks, dronedarone produced the most pronounced reduction in systolic and diastolic blood pressure, while amiodarone and dofetilide significantly reduced systolic blood pressure.
Ex vivo, dofetilide significantly increased dp/dt max across all coronary perfusion pressures compared to untreated controls, whereas dronedarone significantly decreased dp/dt max, heart rate, and coronary flow across all pressure levels.
Dofetilide exhibited the lowest myocardial HSP70 immunoreactivity, the highest SERCA2 expression, significantly reduced superoxide levels across all perfusion pressures, and elevated systemic glutathione.

Structured PICO

Do class III antiarrhythmic drugs (dronedarone, amiodarone, dofetilide) improve cardiac function, redox balance, and myocardial remodeling in spontaneously hypertensive rats?

P

Population

24 male spontaneously hypertensive rats, aged 6-8 weeks, were treated for 4 weeks to evaluate the effects of class III antiarrhythmic drugs on cardiac function and oxidative stress.

I

Intervention

Dronedarone 10 mg/kg, amiodarone 10 mg/kg, or dofetilide 10 mg/kg administered daily by oral gavage for 4 weeks.

C

Comparator

Untreated SHR group receiving saline at equivalent dose daily by oral gavage for 4 weeks.

O

Outcome

Cardiac function (in vivo by echocardiography and ex vivo using Langendorff model), oxidative stress markers, myocardial morphology, and HSP70 and SERCA2 expression.surrogate

Class III antiarrhythmics exhibit distinct effects on cardiac function, redox balance, and myocardial remodeling in hypertensive rats, highlighting potential cardioprotective mechanisms beyond ion channel blockade.

Limitations

Use of a genetic model of essential hypertension limits generalizability to other etiological forms of hypertension.
Small sample size (n = 6 per group) may have limited statistical power to detect subtle inter-group differences.
Absence of a normotensive control group.
The Langendorff model does not fully recapitulate in vivo neurohumoral regulation.
The four-week treatment duration may not capture the full extent of long-term remodeling processes.
Lack of direct electrophysiological measurements such as surface ECG recordings or proarrhythmia susceptibility testing.
Small sample size (6 animals per group) limiting statistical power to detect subtle differences

Implication

Should not yet change antiarrhythmic selection in hypertension; leaves open differential class III effects for human translation.

Abstract

Arterial hypertension is a well-known risk factor for cardiac arrhythmias, while certain antihypertensive agents may also create conditions for arrhythmia occurrence. The aim of this study was to evaluate the effects of selected class III antiarrhythmic drugs on cardiac function and structure, as well as on oxidative stress status, in spontaneously hypertensive rats (SHRs). Male SHRs were treated for 4 weeks with dronedarone, amiodarone, or dofetilide. Cardiac function was assessed in vivo by echocardiography and ex vivo using the Langendorff model. Oxidative stress markers, myocardial morphology, and HSP70 and SERCA2 expression were analyzed. All drugs partially improved cardiac function in vivo, with dronedarone exerting the strongest antihypertensive effect. Ex vivo, dofetilide enhanced contractility and dronedarone reduced cardiac performance, whereas amiodarone showed intermediate effects. Oxidative stress was differentially modulated, with dofetilide and amiodarone improving antioxidant defenses, while dronedarone showed heterogeneous effects. Histologically, dofetilide preserved myocardial architecture most effectively, while amiodarone and dronedarone partially attenuated hypertensive remodeling. Treatments decreased HSP70 expression, while increasing SERCA2 expression, particularly in the dofetilide group. Class III antiarrhythmic drugs differentially affect cardiac function, redox balance, calcium handling, and myocardial remodeling in hypertension, which may contribute to their distinct antiarrhythmic and cardioprotective properties.

Discussion

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Cite This Study

Simović et al. (2026) studied Arterial hypertension (n=24). Class III antiarrhythmic drugs (dronedarone, amiodarone, dofetilide) vs. Saline (untreated SHR group) was evaluated. Class III antiarrhythmics differentially modulated cardiac function and redox balance in spontaneously hypertensive rats, with dofetilide most effectively preserving myocardial architecture.

synapsesocial.com/papers/6a61b056faa9903c5116af05 https://doi.org/10.3390/ijms27146490

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Effects of Antiarrhythmics on Cardiac Phenotype and Redox Balance in Spontaneously Hypertensive Rats

Figures

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

Effects of Antiarrhythmics on Cardiac Phenotype and Redox Balance in Spontaneously Hypertensive Rats

Figures

Key Points

Structured PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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