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The role of acute hyperinsulinemia in the development of cardiac arrhythmias

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Abstract

Patients with perturbed metabolic control are more prone to develop cardiac rhythm disturbances. The main purpose of the present preclinical study was to investigate the possible role of euglycemic hyperinsulinemia in development of cardiac arrhythmias. Euglycemic hyperinsulinemia was induced in conscious rabbits equipped with a right ventricular pacemaker electrode catheter by hyperinsulinemic euglycemic glucose clamp (HEGC) applying two different rates of insulin infusion (5 and 10 mIU/kg/min) and variable rate of glucose infusion to maintain euglycemia (5.5 ± 0.5 mmol/l). The effect of hyperinsulinemia on cardiac electrophysiological parameters was continuously monitored by means of 12-lead surface ECG recording. Arrhythmia incidence was determined by means of programmed electrical stimulation (PES). The possible role of adrenergic activation was investigated by determination of plasma catecholamine levels and intravenous administration of a beta adrenergic blocking agent, metoprolol. All of the measurements were performed during the steady-state period of HEGC and subsequent to metoprolol administration. Both 5 and 10 mIU/kg/min insulin infusion prolonged significantly QTend, QTc, and Tpeak–Tend intervals. The incidence of ventricular arrhythmias generated by PES was increased significantly by euglycemic hyperinsulinemia and exhibited linear relationship to plasma levels of insulin. No alteration on plasma catecholamine levels could be observed; however, metoprolol treatment restored the prolonged QTend, QTc, and Tpeak–Tend intervals and significantly reduced the hyperinsulinemia-induced increase of arrhythmia incidence. Euglycemic hyperinsulinemia can exert proarrhythmic effect presumably due to the enhancement of transmural dispersion of repolarization. Metoprolol treatment may be of benefit in hyperinsulinemia associated with increased incidence of cardiac arrhythmias.

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Acknowledgments

This study was supported by the Hungarian National Office for Research and Technology (NKFP_07-A2-2008-0260, GOP-1.1.2-07/1-2008-0004, TÁMOP-4.2.2.-08/1-2008-0014, OM-00174/2008, TÁMOP-4.2.2/B-10/1-2010-0024, GOP-1.1.1-07/1-2008-0032, and GOP-1.2.1-08-2009-0023) and the Hungarian Scientific Research Fund (OTKA-75965).

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Authors and Affiliations

  1. Department of Pharmacology and Pharmacotherapy, University of Debrecen, Medical, Health and Science Center, H-4032, Nagyerdei Blvd. 98, Debrecen, Hungary

    László Drimba, Csaba Hegedüs, Réka Sári, Yin Di, Joseph Németh, Zoltán Szilvássy & Barna Peitl

  2. Pharmapolis Ltd, H-4032, Nagyerdei Blvd. 98, Debrecen, Hungary

    László Drimba, Réka Sári, Yin Di & Barna Peitl

  3. Department of Anaesthesiology and Intensive Care Unit, Petz Aladár County Hospital, Győr, H-9002, Vasvári P. u. 2, Győr, Hungary

    Róbert Döbrönte

  4. Department of Anesthesiology, Intensive Care Unit and Pain Therapy, Marienhospital, 59302, Oelde, Spellerstraße 16, Germany

    Róbert Döbrönte

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  1. László Drimba
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  2. Róbert Döbrönte
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  3. Csaba Hegedüs
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  4. Réka Sári
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  5. Yin Di
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  6. Joseph Németh
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  7. Zoltán Szilvássy
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  8. Barna Peitl
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Correspondence to László Drimba.

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Drimba, L., Döbrönte, R., Hegedüs, C. et al. The role of acute hyperinsulinemia in the development of cardiac arrhythmias. Naunyn-Schmiedeberg's Arch Pharmacol 386, 435–444 (2013). https://doi.org/10.1007/s00210-013-0845-4

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  • DOI: https://doi.org/10.1007/s00210-013-0845-4

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