IJPPP Copyright © 2009-All rights reserved. Published by e-Century Publishing Corporation, Madison, WI 53711
Int J Physiol Pathophysiol Pharmacol 2013;5(1):52-60

Original Article
Rabbit ventricular myocardium undergoing simulated ischemia and reperfusion in a
double compartment tissue bath: a model to investi-gate both antiarrhythmic and
arrhythmogenic likelihood

Joachim Alexandre, Michele Schiariti, René Rouet, Paolo Emilio Puddu

CHU de Caen, Department of Cardiology, F-14000 Caen, France; Department of Cardiovascular, Respiratory, Nephrological,
Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Viale del Policlinico 155, I-00161 Rome, Italy; Université de
Caen Basse-Normandie, EA 4650 Signalisation, électrophysiologie et imagerie des lésions d’ischémie-reperfusion myocardique, F-
14000 Caen, France

Received January 9, 2013; Accepted February 16, 2013; Epub March 8, 2013; Published March 18, 2013

Abstract: An ischemia/reperfusion-simulating model in rabbit tissue should be right oriented and clinically relevant to provide a non
expensive approach for manipulations of currents involved in the repolarization process. Standard right ventricular guinea-pig (N=18)
and newly investigated rabbit (N=12) myocardial strips were placed in a special perfusion chamber allowing partition into two
segments independently superfused with oxygenated Tyrode’s solution or a modified Tyrode’s solution mimicking ischemia by: 1)
increased extracellular potassium concentration (12 mmol/L), 2) decreased HCO3- concentration (9 mmol/L), leading to a decrease in
pH (6.90 ± 0.05), 3) decreased pO2 by replacement of 95% O2 and 5% CO2 by 95% N2 and 5% CO2 gas mixture, and 4) complete
withdrawal of glucose. There were significant differences in rabbit as compared to guinea-pig preparations in baseline (p<0.02) and
post-ischemic-like (p<0.01) APA and RMP with lower values in the formers, and lower post-ischemic Vmax in rabbit preparations
(25±15 versus 97±83 V/s, p<0.01) but neither baseline nor post-ischemic-like or absolute changes in APD50, APD90 were different. In
ischemia- and reperfusion-like phases, there were high proportions of single spontaneous repetitive responses, both in guinea-pig
(respectively 50 and 89%) and rabbit preparations (respectively 67 and 92%). Guinea-pig preparations showed higher incidence of
severe spontaneous repetitive responses (61 versus 17%, p<0.02). This rabbit model is proposed to investigate both anti- and pro-
arrhythmic effects of drugs acting at various levels electrophysiologically, which may be obtained with great power and relatively few
(around 10 per group) preparations. This model should now be tested pharmacologically. (IJPPP1301002)

Keywords: Electrophysiology in vitro, action potentials, repetitive responses, rabbit, guine-pig, ventricular myocardium, simulated
ischemia

Address correspondence to: Dr. Paolo Emilio Puddu, FESC, FACC, Laboratory of Biotechnologies Applied to Cardiovascular Medicine,
Depart-ment of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome,
Viale del Policlinico, 155, Roma 00161, Italy. Phone: +39.06.49972659; Fax: +39.06.4453891; E-mail: paoloemilio.puddu@uniroma1.it