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Am J Physiol Heart Circ Physiol 293: H875-H880, 2007. First published March 16, 2007; doi:10.1152/ajpheart.01415.2006
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INNOVATIVE METHODOLOGY

Optical mapping of Langendorff-perfused human hearts: establishing a model for the study of ventricular fibrillation in humans

Kumaraswamy Nanthakumar,1 José Jalife,3 Stéphane Massé,1 Eugene Downar,1 Mihaela Pop,1 John Asta,1 Heather Ross,1 Vivek Rao,1 Sergey Mironov,3 Elias Sevaptsidis,1 Jack Rogers,2 Graham Wright,1 and Rajesh Dhopeshwarkar1

1University of Toronto, Toronto, Canada; 2University of Alabama at Birmingham, Birmingham, Alabama; and 3SUNY Upstate Medical University, Syracuse, New York

Submitted 26 December 2006 ; accepted in final form 16 March 2007

Our objective was to establish a novel model for the study of ventricular fibrillation (VF) in humans. We adopted the established techniques of optical mapping to human ventricles for the first time to determine whether human VF is the result of wave breaks and singularity point formation and is maintained by high-frequency rotors and fibrillatory conduction. We describe the technique of acquiring optical signals in human hearts during VF, their characteristics, and the feasibility of possible analyses that could be performed to elucidate mechanisms of human VF. We used explanted hearts from five cardiomyopathic patients who underwent transplantation. The hearts were Langendorff perfused with Tyrode solution (95% O2-5% CO2), and the potentiometric dye di-4-ANEPPS was injected as a bolus into the coronary circulation. Fluorescence was excited at 531 ± 20 nm with a 150-W halogen light source; the emission signal was long-pass filtered at 610 nm and recorded with a mapping camera. Fractional change of fluorescence varied between 2% and 12%. Average signal-to-noise ratio was 40 dB. The mean velocity of VF wave fronts was 0.25 ± 0.04 m/s. Submillimetric spatial resolution (0.65–0.85 mm), activation mapping, and transformation of the data to phase-based analysis revealed reentrant, colliding, and fractionating wave fronts in human VF. On many occasions the VF wave fronts were as large as the entire vertical length (8 cm) of the mapping field, suggesting that there are a limited number of wave fronts on the human heart during VF. Phase transformation of the optical signals allowed the first demonstration ever of phase singularity point, wave breaks, and rotor formation in human VF. This method provides opportunities for potential analyses toward elucidation of the mechanisms of VF and defibrillation in humans.

rotors; action potential duration; conduction block


Address for reprint requests and other correspondence: K. Nanthakumar, Div. of Cardiology, University Health Network, Toronto General Hosp., 150 Gerrard St. W, Gerrard Wing 3-522, Toronto, ON, Canada M5G 2C4 (e-mail: k.nanthakumar{at}uhn.on.ca)




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