Mouse ECG findings in aging, with conduction system affecting drugs and in cardiac pathologies: Development and validation of ECG analysis algorithm in mice

Mouse models are extremely important in studying cardiac pathologies and related electrophysiology, but very few mouse ECG analysis programs are readily available. Therefore, a mouse ECG analysis algorithm was developed and validated. Surface ECG (lead II) was acquired during transthoracic echocardiography from C57Bl/6J mice under isoflurane anesthesia. The effect of aging was studied in young (2–3 months), middle‐aged (14 months) and old (20–24 months) mice. The ECG changes associated with pharmacological interventions and common cardiac pathologies, that is, acute myocardial infarction (AMI) and progressive left ventricular hypertrophy (LVH), were studied. The ECG raw data were analyzed with an in‐house ECG analysis program, modified specially for mouse ECG. Aging led to increases in P‐wave duration, atrioventricular conduction time (PQ interval), and intraventricular conduction time (QRS complex width), while the R‐wave amplitude decreased. In addition, the prevalence of arrhythmias increased during aging. Anticholinergic atropine shortened PQ time, and beta blocker metoprolol and calcium‐channel blocker verapamil increased PQ interval and decreased heart rate. The ECG changes after AMI included early JT elevation, development of Q waves, decreased R‐wave amplitude, and later changes in JT/T segment. In progressive LVH model, QRS complex width was increased at 2 and especially 4 weeks timepoint, and also repolarization abnormalities were seen. Aging, drugs, AMI, and LVH led to similar ECG changes in mice as seen in humans, which could be reliably detected with this new algorithm. The developed method will be very useful for studies on cardiovascular diseases in mice.

[1]  S. Fisher,et al.  QRS duration and mortality in patients with congestive heart failure. , 2002, American heart journal.

[2]  Ruben Coronel,et al.  Early repolarization in mice causes overestimation of ventricular activation time by the QRS duration. , 2013, Cardiovascular research.

[3]  M. Vos,et al.  Heterogeneous Connexin43 distribution in heart failure is associated with dispersed conduction and enhanced susceptibility to ventricular arrhythmias , 2010, European journal of heart failure.

[4]  S. Verheule,et al.  Cardiac electrophysiology in mice: a matter of size , 2012, Front. Physio..

[5]  Linda Teplitz,et al.  The Only EKG Book You'll Ever Need , 1989 .

[6]  P. Ellinor,et al.  A Novel Transgenic Mouse Model of Cardiac Hypertrophy and Atrial Fibrillation. , 2012, Journal of atrial fibrillation.

[7]  K. Svenson,et al.  Genetic influence on electrocardiogram time intervals and heart rate in aging mice. , 2009, American journal of physiology. Heart and circulatory physiology.

[8]  D. L. Wilson,et al.  C57BL/6 mice fed high fat diets as models for diabetes-accelerated atherosclerosis. , 1998, Atherosclerosis.

[9]  Ruben Coronel,et al.  Misinterpretation of the mouse ECG: ‘musing the waves of Mus musculus’ , 2014, The Journal of physiology.

[10]  Per Capita,et al.  About the authors , 1995, Machine Vision and Applications.

[11]  J. Alpert,et al.  Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction , 2008 .

[12]  Malcolm S. Thaler Comprar The Only Ekg Book You'll Ever Need 7th Ed. | Malcolm S. Thaler | 9781451119053 | Lippincott Williams & Wilkins , 2012 .

[13]  H. Duff,et al.  In vivo temporal and spatial distribution of depolarization and repolarization and the illusive murine T wave , 2004, The Journal of physiology.

[14]  Polina Sysa-Shah,et al.  Cardiac-Specific Over-Expression of Epidermal Growth Factor Receptor 2 (ErbB2) Induces Pro-Survival Pathways and Hypertrophic Cardiomyopathy in Mice , 2012, PloS one.

[15]  Aldebaro Klautau,et al.  New approach for T-wave end detection on electrocardiogram: Performance in noisy conditions , 2011, Biomedical engineering online.

[16]  W. Koch,et al.  A Novel and Efficient Model of Coronary Artery Ligation and Myocardial Infarction in the Mouse , 2010, Circulation research.

[17]  M. Scherrer-Crosbie,et al.  Echocardiography in translational research: of mice and men. , 2008, Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography.

[18]  Yu-Ming Li,et al.  Characterization of atrial histopathological and electrophysiological changes in a mouse model of aging. , 2013, International journal of molecular medicine.

[19]  M. Thomsen,et al.  Physiology and analysis of the electrocardiographic T wave in mice , 2013, Acta physiologica.

[20]  S. Broyles,et al.  Electrocardiographic findings in 888 patients > or =90 years of age. , 2006, The American journal of cardiology.

[21]  P. Doevendans,et al.  Mouse electrocardiography: an interval of thirty years. , 2000, Cardiovascular research.

[22]  J. Fleg,et al.  Age-associated changes in the components of atrioventricular conduction in apparently healthy volunteers. , 1990, Journal of gerontology.

[23]  Maarten L. Simoons,et al.  The third universal definition of myocardial infarction , 2013 .

[24]  Richard T. Lee,et al.  Electrophysiological characterization of murine myocardial ischemia and infarction , 2001, Basic Research in Cardiology.

[25]  G. Mitchell,et al.  Measurement of heart rate and Q-T interval in the conscious mouse. , 1998, American journal of physiology. Heart and circulatory physiology.

[26]  K. Alitalo,et al.  AAV9-mediated VEGF-B gene transfer improves systolic function in progressive left ventricular hypertrophy. , 2012, Molecular therapy : the journal of the American Society of Gene Therapy.

[27]  Mika P. Tarvainen,et al.  Kubios HRV - Heart rate variability analysis software , 2014, Comput. Methods Programs Biomed..

[28]  S. Mohiuddin,et al.  Electrocardiographic findings in patients >100 years of age without clinical evidence of cardiac disease. , 2003, The American journal of cardiology.

[29]  Spencer J. Dech,et al.  Age and anesthetic effects on murine electrocardiography. , 2003, Life sciences.

[30]  T. Opthof,et al.  Larger Cell Size in Rabbits With Heart Failure Increases Myocardial Conduction Velocity and QRS Duration , 2006, Circulation.