Development and characterization of a mouse in vitro model of ischaemia-induced ventricular fibrillation

Catherine L Stables, Michael J Curtis

Research output: Contribution to journalArticlepeer-review

Abstract

AIMS: We sought to generate a mouse Langendorff model of ischaemia-induced ventricular fibrillation (VF) that does not depend on triggers such as programmed electrical stimulation.

METHODS AND RESULTS: Hearts from male Tuck Ordinary mice were perfused with Krebs solution (modified to contain low-normal K(+), 3 mmol/L, and high Ca(2+), 2.4 mmol/L) containing different combinations of catecholamines (epinephrine 313 nmol/L plus norepinephrine 75 nmol/L) and/or angiotensin II (100 pmol/L) designed to mimic the in vivo milieu. VF was absent during 30 min regional ischaemia (and during 10 min reperfusion) in Krebs-perfused hearts. Catecholamines unmasked ischaemia-induced VF (50%; P < 0.05) and reperfusion-induced VF (50%; P < 0.05). Co-perfusion with angiotensin II did not facilitate VF. Supraventricular pacing (600 b.p.m.) stabilized pre-ischaemic sinus rhythm and partially mimicked the VF-unmasking effect of catecholamines. Arrhythmia susceptibility was greatest with supraventricular pacing plus catecholamines (57% VF during ischaemia and 71% during reperfusion).

CONCLUSION: For the first time, regional ischaemia-induced VF was consistently evoked in a mouse Langendorff preparation, unmasked by simple periphysiological manipulation of the perfusion conditions. The model is suitable for functional genomic studies.

Original languageEnglish
Pages (from-to)397-404
Number of pages8
JournalCardiovascular Research
Volume83
Issue number2
DOIs
Publication statusPublished - 15 Jul 2009

Keywords

  • Angiotensin II
  • Animals
  • Cardiac Pacing, Artificial
  • Catecholamines
  • Disease Models, Animal
  • Electrocardiography
  • Heart Rate
  • Male
  • Mice
  • Myocardial Ischemia
  • Myocardial Reperfusion
  • Myocardial Reperfusion Injury
  • Perfusion
  • Time Factors
  • Ventricular Fibrillation

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