Name: methods for ecg evaluation of indicators of cardiac risk, and susceptibility to aconitine-induced arrhythmias in rats following status epilepticus
Uploaded: 2011-04-05T13:00:00
Description: Watch this Scientific Journal Video about Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus at JoVE.com

This research was supported by a grant from the Citizens United for Research in Epilepsy (CURE) to SLB.

1. Materials to Construct
 <ol>
	<li>A jugular vein catheter is constructed from a piece (100 mm) of PE-50 polyethylene tubing, beveled at one end, and then filled with heparin saline (50 U heparin/mL saline).</li>
	<li>The ECG recording electrodes are constructed from two 100 mm lengths of insulated silver wire (30AWG). One end of both wires is stripped and soldered to a microconnector, and the insulation is twisted to form a third wire that is used as ground. Five-mm of insulation is stripped from the distal end of...

<ol>
	<li>Chugh, S. S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determinants+of+prolonged+QT+interval+and+their+contribution+to+sudden+death+risk+in+coronary+artery+disease:+The+Oregon+sudden+unexpected+death+study.">Determinants of prolonged QT interval and their contribution to sudden death risk in coronary artery disease: The Oregon sudden unexpected death study.</a> Circulation. 119, 663-670 (2009).</li><li>Darbar, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sensitivity+and+specificity+of+QTc+dispersion+for+identification+of+risk+of+cardiac+death+in+patients+with+peripheral+vascular+disease.">Sensitivity and specificity of QTc dispersion for identification of risk of cardiac death in patients with peripheral vascular disease.</a> BMJ. 312, 874-878 (1996).</li><li>Bruyne, M. C. d. e. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=QTc+dispersion+predicts+cardiac+mortality+in+the+elderly:+The+Rotterdam+study.">QTc dispersion predicts cardiac mortality in the elderly: The Rotterdam study.</a> Circulation. 97, 467-472 (1998).</li><li>Malik, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Heart+rate+variability:+standards+of+measurement,+physiological+interpretation,+and+clinical+use.">Heart rate variability: standards of measurement, physiological interpretation, and clinical use.</a> Circulation. 93, 1043-1065 (1996).</li><li>Grippo, A. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Increased+susceptibility+to+ventricular+arrhythmias+in+a+rodent+model+of+experimental+depression.">Increased susceptibility to ventricular arrhythmias in a rodent model of experimental depression.</a> Am. J. Physiol. 286, H619-H626 (2004).</li><li>Li, M., Wang, J., Xie, H. H., Shen, F. M., Su, D. F. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+susceptibility+of+ventricular+arrhythmia+to+aconitine+in+conscious+hypertensive+rats.">The susceptibility of ventricular arrhythmia to aconitine in conscious hypertensive rats.</a> Acta. 28, 211-215 (2007).</li><li>Beig, M. I. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Voluntary+exercise+does+not+affect+stress-induced+tachycardia,+but+improves+resistance+to+cardiac+arrhythmias+in+rats.">Voluntary exercise does not affect stress-induced tachycardia, but improves resistance to cardiac arrhythmias in rats.</a> Clin. Exp. Pharm. Physiol. , (2010).</li><li>Hazari, M. S., Haykai-Coates, N., Winsett, D. W., Costa, D. L., Farraj, A. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+single+exposure+to+particulate+or+gaseous+ari+pollution+increases+the+risk+of+aconitine-induced+cardiac+arrhythmia+in+hypertensive+rats.">A single exposure to particulate or gaseous ari pollution increases the risk of aconitine-induced cardiac arrhythmia in hypertensive rats.</a> Toxicol. Sci. 112, 532-542 (2009).</li><li>Amran, M. S., Hashimoto, K., Homma, N. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Effects+of+sodium-calcium+exchange+inhibitors,+KB-R7943+and+SEA0400,+on+aconitine-induced+arrhythmias+in+guinea+pigs+in+vivo,+in+vitro,+and+in+computer+simulation+studies.">Effects of sodium-calcium exchange inhibitors, KB-R7943 and SEA0400, on aconitine-induced arrhythmias in guinea pigs in vivo, in vitro, and in computer simulation studies.</a> J. Pharmacol. Exp. Ther. 310, 83-89 (2004).</li><li>Klekot, A. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Antiarrhythmic+activity+of+a+membrane-protecting+agent+Sal'magin+in+rats+with+aconitine-induced+arrhythmias.">Antiarrhythmic activity of a membrane-protecting agent Sal'magin in rats with aconitine-induced arrhythmias.</a> Bull. Exp. Biol. Med. 142, 209-211 (2006).</li><li>Lowenstein, D. H., Alldredge, B. K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+Epilepticus.">Status Epilepticus.</a> New England J. Med. 338, 970-976 (1998).</li><li>Walker, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+epilepticus:+an+evidence+based+guide.">Status epilepticus: an evidence based guide.</a> BMJ. 331, 673-677 (2005).</li><li>Shorvon, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Status epilepticus: its clinical features and treatment in children and adults. , (1994).</li><li>Boggs, J. G. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hemodynamic+monitoring+prior+to+and+at+the+time+of+death+in+status+epilepticus.">Hemodynamic monitoring prior to and at the time of death in status epilepticus.</a> Epilepsy Res. 31, 199-209 (1998).</li><li>Walton, N. Y. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Systemic+effects+of+generalized+convulsive+status+epilepticus.">Systemic effects of generalized convulsive status epilepticus.</a> Epilepsia. 34, S54-S58 (1993).</li><li>Boggs, J. G., Painter, J. A., DeLorenzo, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Analysis+of+electrocardiographic+changes+in+status+epilepticus.">Analysis of electrocardiographic changes in status epilepticus.</a> Epilepsy Res. 14, 87-94 (1993).</li><li>Painter, J. A., Shiel, F. O., DeLorenzo, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Cardiac+pathology+findings+in+status+epilepticus.">Cardiac pathology findings in status epilepticus.</a> Epilepsia. 34, 30-30 (1993).</li><li>Lathers, C. M., Schraeder, P. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Clinical+pharmacology:+drugs+as+a+benefit+and/or+risk+in+sudden+unexpected+death+in+epilepsy.">Clinical pharmacology: drugs as a benefit and/or risk in sudden unexpected death in epilepsy.</a> J. Clin. Pharmacol. 42, 123-126 (2002).</li><li>Dashieff, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sudden+unexpected+death+in+epilepsy:+a+series+from+an+epilepsy+surgery+program+and+specualtion+of+the+relationship+to+sudden+cardiac+death.">Sudden unexpected death in epilepsy: a series from an epilepsy surgery program and specualtion of the relationship to sudden cardiac death.</a> J. Clin. Neurophysiol. 8, 216-222 (1991).</li><li>Tigaran, P. -. C. o. d. r. e. a., Dalager-Pedersen, S., Baandrup, S., Dam, U., M, ., Vesterby-Charles, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Sudden+unexpected+death+in+epilepsy:+is+death+by+seizures+a+cardiac+event.">Sudden unexpected death in epilepsy: is death by seizures a cardiac event.</a> Am. J. Forensic Med. Pathol. 26, 99-105 (2005).</li><li>Leung, H., Kwan, P., Elger, C. E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Finding+the+missing+link+between+ictal+bradyarrhythmia,+ictal+asystole,+and+sudden+unexpected+death+in+epilepsy.">Finding the missing link between ictal bradyarrhythmia, ictal asystole, and sudden unexpected death in epilepsy.</a> Epilepsy and Behavior. 9, 19-30 (2006).</li><li>Nei, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=EEG+and+ECG+in+sudden+unexplained+death+in+epilepsy.">EEG and ECG in sudden unexplained death in epilepsy.</a> Epilepsia. 45, 338-345 (2004).</li><li>Dudek, F. E., Clark, S., Williams, P. A., Grabenstatter, H. L., Pitkanen, A., Schwartzkroin, P. A., Moshe, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=.">.</a> Models of Seizures and Epilepsy. , 415-432 (2006).</li><li>Turski, W. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Limbic+seizures+produced+by+pilocarpine+in+rats:+behavioral+electroencephalographic,+and+neuropathological+study.">Limbic seizures produced by pilocarpine in rats: behavioral electroencephalographic, and neuropathological study.</a> Behav. Brain Res. 9, 315-335 (1989).</li><li>Kulkarni, S. K., George, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Lithium-pilocarpine+neurotoxicity:+a+potential+model+of+status+epilepticus.">Lithium-pilocarpine neurotoxicity: a potential model of status epilepticus.</a> Methods Find. Exp. Clin. Pharamacol. 17, 551-567 (1995).</li><li>Stein, P. K., Bosner, M. S., Kleiger, R. E., Conger, B. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Hart+rate+variability:+a+measure+of+cardiac+autonomic+tone.">Hart rate variability: a measure of cardiac autonomic tone.</a> Am. Heart J. 127, 1376-1381 (1994).</li><li>Metcalf, C. S., Poelzing, S., Little, J. G., Bealer, S. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Status+epilepticus+induces+cardiac+myofilament+damage+and+increased+susceptibility+to+arrhythmias+in+rat.">Status epilepticus induces cardiac myofilament damage and increased susceptibility to arrhythmias in rat.</a> Am. J. Physiol. 297, H2120-H2127 (2009).</li></ol>

Two aspects of the described procedures are of critical importance. Firstly, the rate of aconitine administration to the 
heart must be equivalent across animals. This requires consistent placement of the jugular vein catheter tips relative to the heart, and careful 
adjustment of the infusion rate. The rate of aconitine delivery to the hearts must be equal in order to appropriately evaluate the onset of 
ventricular arrhythmias relative to altered susceptibility. If aconitine delivery varies, then the latency to arrhyt...

methods for ecg evaluation of indicators of cardiac risk, and susceptibility to aconitine-induced arrhythmias in rats following status epilepticus

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily obtained electrocardiogram (ECG) are established, well-validated prognostic indicators of cardiac risk in patients suffering 
from a number of cardiomyopathies. Increased heart rate, decreased heart rate variability (HRV), and increased duration and variability of cardiac 
ventricular electrical activity (QT interval) are all indicative of enhanced cardiac risk 1-4. In animal models, it is valuable to compare 
these ECG-derived variables and susceptibility to experimentally induced arrhythmias. Intravenous infusion of the arrhythmogenic agent aconitine has
 been widely used to evaluate susceptibility to arrhythmias in a range of experimental conditions, including animal models of depression 5 and 
 hypertension 6, following exercise 7 and exposure to air pollutants 8, as well as determination of the antiarrhythmic efficacy of pharmacological 
 agents 9,10. 
It should be noted that QT dispersion in humans is a measure of QT interval variation across the full set of leads from a 
standard 12-lead ECG. Consequently, the measure of QT dispersion from the 2-lead ECG in the rat described in this protocol is different than that 
calculated from human ECG records. This represents a limitation in the translation of the data obtained from rodents to human clinical medicine.
Status epilepticus (SE) is a single seizure or series of continuously recurring seizures lasting more than 30 min 
11,12 11,12, and results in mortality in 20% of cases 13. Many individuals survive the SE, but die within 30 days 14,15.
 The mechanism(s) of this delayed mortality is not fully understood. It has been suggested that lethal ventricular arrhythmias contribute to many of these 
 deaths 14-17. In addition to SE, patients experiencing spontaneously recurring seizures, i.e. epilepsy, are at risk of premature 
 sudden and unexpected death associated with epilepsy (SUDEP) 18. As with SE, the precise mechanisms mediating SUDEP are not known. 
 It has been proposed that ventricular abnormalities and resulting arrhythmias make a significant contribution 18-22.
 To investigate the mechanisms of seizure-related cardiac death, and the efficacy of cardioprotective therapies, it is 
 necessary to obtain both ECG-derived indicators of risk and evaluate susceptibility to cardiac arrhythmias in animal models of seizure disorders 
 23-25. Here we describe methods for implanting ECG electrodes in the Sprague-Dawley laboratory rat (Rattus norvegicus), following SE,
 collection and analysis of ECG recordings, and induction of arrhythmias during iv infusion of aconitine.
 These procedures can be used to directly determine the relationships between ECG-derived measures of cardiac electrical 
 activity and susceptibility to ventricular arrhythmias in rat models of seizure disorders, or any pathology associated with increased risk of sudden 
 cardiac death.

Watch this Scientific Journal Video about Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus at JoVE.com

Methods for ECG Evaluation of Indicators of Cardiac Risk, and Susceptibility to Aconitine-induced Arrhythmias in Rats Following Status Epilepticus

Techniques for measurement of electrical activity of the heart by electrocardiogram (ECG), and analysis of cardiac risk factors and susceptibility to arrhythmias following status epilepticus (SE) in the rat are described.

Lethal cardiac arrhythmias contribute to mortality in a number of pathological conditions. Several parameters obtained from a 
non-invasive, easily ...

Research

JoVE Journal

Medicine

Gene-environment Interaction Models to Unmask Susceptibility Mechanisms in Parkinson's Disease

Lipoxygenase (LOX) activity has been implicated in neurodegenerative disorders such as Alzheimer&#39;s disease, but its effects in Parkinson&#39;s disease ...

Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model

Ascending aortic constriction is the most common and successful surgical model for creating pressure overload induced cardiac hypertrophy and heart ...

Early Detection of Drug-Induced Renal Hemodynamic Dysfunction Using Sonographic Technology in Rats

The kidney normally functions to maintain hemodynamic homeostasis and is a major site of damage caused by drug toxicity. Drug-induced nephrotoxicity is ...

A Model of Cardiac Remodeling Through Constriction of the Abdominal Aorta in Rats

Heart failure is one of the leading causes of death worldwide. It is a complex clinical syndromethat includes fatigue, dyspnea, exercise intolerance, and ...

Cardiac Magnetic Resonance for the Evaluation of Suspected Cardiac Thrombus: Conventional and Emerging Techniques

We present the conventional cardiac magnetic resonance (CMR) protocol for evaluating a suspected thrombus and highlight emerging techniques.&#160;The ...

Echocardiographic Assessment of Cardiac Anatomy and Function in Adult Rats

The use of experimental animal models has become crucial in cardiovascular science. Most studies using rodent models are focused on two-dimensional ...

Semi-Minimal Invasive Method to Induce Myocardial Infarction in Rats and the Assessment of Cardiac Function by an Isolated Working Heart System

Myocardial infarction (MI) remains the main contributor to morbidity and mortality worldwide. Therefore, research on this topic is mandatory. An easily ...

Development and Evaluation of 3D-Printed Cardiovascular Phantoms for Interventional Planning and Training

Catheter-based interventions are standard treatment options for cardiovascular pathologies. Therefore, patient-specific models could help training ...

Implantation of Combined Telemetric ECG and Blood Pressure Transmitters to Determine Spontaneous Baroreflex Sensitivity in Conscious Mice

Blood pressure (BP) and heart rate (HR) are both controlled by the autonomic nervous system (ANS) and are closely intertwined due to reflex mechanisms. ...

Analyzing Long-Term Electrocardiography Recordings to Detect Arrhythmias in Mice

Arrhythmias are common, affecting millions of patients worldwide. Current treatment strategies are associated with significant side effects and remain ...