What is the clinical evidence from this study?

Population: Ventricular arrhythmias (n=23). Intervention: Isoproterenol vs. NaCl (0.9%, 5 ml/kg body weight, i.p.). Primary outcome: Occurrence of ventricular arrhythmias (p=<0.05).

January 29, 2018Scientific ReportsOpen Access

Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation

Q: What are the key findings of this study?

Following beta-adrenergic stimulation with isoproterenol, Balb/c mice developed a significantly higher burden of ventricular arrhythmias compared to BS, C57Bl/6, and FVB mice.

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Key result

Following beta-adrenergic stimulation with isoproterenol, Balb/c mice developed a significantly higher burden of ventricular arrhythmias compared to BS, C57Bl/6, and FVB mice.

Structured PICO

Population

23 healthy male mice from 4 genetic strains (Balb/c, C57Bl/6, BS, FVB) aged 7-10 weeks were evaluated for susceptibility to ventricular arrhythmias following beta-adrenergic stimulation.

Intervention

β-adrenergic stimulation with isoproterenol (2 mg/kg body weight, i.p.) and β-adrenergic blockade with metoprolol (100 mg/kg body weight per day, p.o.)

Comparator

Sham-injection of NaCl

Outcome

Occurrence and complexity of ventricular arrhythmias (premature ventricular beats, coupled beats, ventricular tachycardic events, and ventricular fibrillation) over 5 hours following isoproterenol injectionsurrogate

Main Result

p-value: p=<0.05

Genetic background strongly influences susceptibility to ventricular arrhythmias in mice, which is critical for selecting appropriate strains in cardiovascular research.

Limitations

Translation of background-specific effects into murine models of cardiac disease or patients is not possible without further experiments.
Differences in the coupling and/or downregulation of beta-adrenergic receptors cannot be ruled out.
Did not use knock-out mice lacking beta1- and/or beta2-adrenoceptors to address potential receptor-independent effects.
Translation of the background specific effects into murine models of cardiac disease or into patients is not possible without further experiments
Lack of knock out mice lacking β1- and/or β2-adrenoceptors to address potential effects of isoproterenol which are independent of cardiac β1- and β2-adrenoceptor

Discussion

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Implication

Requires strain-specific controls in murine arrhythmia models; leaves open identification of genetic modifiers for clinical translation.

Cite This Study

Jelinek et al. (2018) studied Ventricular arrhythmias (n=23). Isoproterenol vs. NaCl (0.9%, 5 ml/kg body weight, i.p.) was evaluated on Occurrence of ventricular arrhythmias (p=<0.05). Following beta-adrenergic stimulation with isoproterenol, Balb/c mice developed a significantly higher burden of ventricular arrhythmias compared to BS, C57Bl/6, and FVB mice.

synapsesocial.com/papers/6a96cc1cd45ba51c86b2ebc6 https://doi.org/10.1038/s41598-018-20792-5

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Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

Genetic background dominates the susceptibility to ventricular arrhythmias in a murine model of β-adrenergic stimulation

Structured PICO

Main Result

Limitations

Discussion

Implication

Cite This Study

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