title: Spatial heterogeneity of calcium transient alternans during the early phase of myocardial ischemia in the blood-perfused rabbit heart.
abstract: BACKGROUND
  Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca(2+)](i) indicators. We propose that beat-to-beat [Ca(2+)](i) transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents.
  
  
  RESULTS
  To test this hypothesis, isolated rabbit hearts were loaded with the fluorescent [Ca(2+)](i) indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca(2+)](i) transients were recorded in each of 8 hearts.[Ca(2+)](i) transient alternans was never present in control records but occurred in each of the hearts during ischemia, with onset after 2 to 4 minutes. Alternans was confined to circumscribed regions of the heart surface 5 to 15 mm across. Multiple regions of alternans were found in most hearts, and regions that were out of phase with one another were found in 6 hearts. Quantitative maps of alternans were constructed by calculating an alternans ratio. This ratio behaved as a continuous variable that reached a maximum value in the center of the regions with alternans.
  
  
  CONCLUSIONS
  These results demonstrate marked spatial heterogeneity of the [Ca(2+)](i) transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts.
authors.affiliation: Cardiovascular Division, Stanford University School of Medicine, Stanford, CA, USA.
authors.forename: Y W
authors.initials: YW
authors.lastname: Qian
authors.forename: W T
authors.initials: WT
authors.lastname: Clusin
authors.forename: S F
authors.initials: SF
authors.lastname: Lin
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: R J
authors.initials: RJ
authors.lastname: Sung
mesh_terms: D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology*; D018780:Body Surface Potential Mapping; D002118:Calcium / Q000378:metabolism*; D004195:Disease Models, Animal; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005456:Fluorescent Dyes; D006329:Heart Conduction System / Q000503:physiopathology*; D006575:Heterocyclic Compounds, 3-Ring; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D008297:Male; D017202:Myocardial Ischemia / Q000150:complications / Q000503:physiopathology*; D011817:Rabbits; D013997:Time Factors
chemical_list: D005456:Fluorescent Dyes; D006575:Heterocyclic Compounds, 3-Ring; C068483:rhod-2; D002118:Calcium