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Am J Physiol Heart Circ Physiol (August 7, 2003). doi:10.1152/ajpheart.00369.2003
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Submitted on April 21, 2003
Accepted on August 1, 2003

Spatial Heterogeneity of Action Potential Alternans During Global Ischemia in the Rabbit Heart

You-wen Qian1, Ruey J. Sung1, Shien-Fong Lin2, Rose Province3, and William T. Clusin1*

1 Department of Cardiology, Stanford University School of Medicine, Stanford, CA, USA
2 Cedars-Sinai Medical Center, Los Angeles, CA, USA
3 St. Jude Medical, Sunnyvale, CA, USA

* To whom correspondence should be addressed. E-mail: wclusin{at}stanford.edu.

Cardiac ischemia causes beat-to-beat fluctuation in action potential duration (APD alternans), which leads to T-wave alternans and arrhythmias. APD alternans that is out of phase at two sites is especially important, but most studies of this have involved rapid pacing of normal myocardium, rather than ischemia. To determine the spatial features of APD alternans during ischemia, blood-perfused rabbit hearts were stained with di-4-ANEPPS, and imaged with a high resolution camera. Hearts were perfused with oxygenated Tyrodes solution at 37° C for staining and then switched to a 50% blood/Tyrode's mixture. Hearts were paced from the right ventricle at 3/sec., and made ische-mic by stopping flow for 6 min. Images of l0,000 pixels were obtained at 300 frames /sec. Motion artifact was controlled by immobilization and by manual selection of undistorted single-pixel records. Upstroke propagation and conduction isochrones were displayed by computerized image processing. APD alternans was demonstrated in 6 of 7 hearts, and was out of phase in different regions of the image in 3 hearts. The largest spatial variation in APD50 was 155%. This caused beat-to-beat reversal of repolariza-tion. An alternans map could be constructed for well-immobilized portions of the image. There were discrete regions of APD alternans separated by a boundary, as occurs with [Ca2+]i alternans. Pixels as close together as 1.1 mm showed APD alter-nans that was out of phase. Out of phase APD alternans was not due to conduction alternans as shown by upstroke intervals and conduction isochrones. This contrasts with rapid pacing, where a causal relationship appears to exist. These new observations suggest distinct mechanisms for the genesis of arrhythmias during ischemia.




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