Increased inducibility of ventricular tachycardia and decreased heart rate variability in a mouse model for type 1 diabetes: Effect of pravastatin

Mohammad Rajab, Hongwei Jin, Charles M. Welzig, Alfred Albano, Mark Aronovitz, Yali Zhang, Ho Jin Park, Mark S. Link, Sami F. Noujaim, Jonas B. Galper

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

Although a reduction in the high-frequency (HF) component of heart rate variability (HRV) is a major complication of diabetes and a risk factor for sudden death, its relationship to ventricular tachycardia (VT) is unknown. We developed a mouse model for the study of VT and its relationship to changes in HRV in the Akita type 1 diabetic mouse. Programmed ventricular stimulation of anesthetized mice demonstrated that Akita mice were more inducible for VT compared with wild-type mice: 78.6% versus 28.6% (P = 0.007). Optical mapping of perfused hearts demonstrated multifocal breakthroughs that occasionally gave rise to short-lived rotors consistent with focal initiation and maintenance of VT. Treatment of Akita mice with pravastatin, which had been previously shown clinically to decrease ventricular ectopy and to increase HRV, decreased the inducibility of VT: 36.8% compared with 75.0% with placebo treatment (P= 0.022). The HF fraction of HRV was reduced in Akita mice (48.6 ±5.2% vs. 70.9 ± 4.8% in wild-type mice, P = 0.005) and was increased compared with placebo treatment in pravastatin-treated mice. Pretreatment of Akita mice with the muscarinic agonist carbamylcholine or the β-adrenergic receptor blocker propranolol decreased the inducibility of VT (P 0.001). In conclusion, the increased inducibility of focally initiated VT and reduced HF fraction in Akita mice were partially reversed by both pravastatin treatment and pharmacologic reversal of parasympathetic dysfunction. In this new animal model for the study of the pathogenesis of VT in type 1 diabetes, pravastatin may play a role in the prevention of VT by attenuating parasympathetic dysfunction.

Original languageEnglish (US)
Pages (from-to)H1807-H1816
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number12
DOIs
StatePublished - Dec 15 2013

Keywords

  • Secondary effects of diabetes
  • Statins
  • Type 1 diabetes
  • Ventricular tachycardia

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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