Circulation. 2001;104:2082-2087
doi: 10.1161/hc4201.097136
doi: 10.1161/hc4201.097136
(Circulation. 2001;104:2082.)
© 2001 American Heart Association, Inc.
Basic Science Reports |
Spatial Heterogeneity of Calcium Transient Alternans During the Early Phase of Myocardial Ischemia in the Blood-Perfused Rabbit Heart
From the Cardiovascular Division, Stanford University School of Medicine, Stanford, Calif, and Department of Physics and Astronomy, Vanderbilt University (S.-F.L.), Nashville, Tenn.
Correspondence to William T. Clusin, MD, PhD, Cardiology Division, CV-265, Stanford University Medical School, 300 Pasteur Dr, Stanford, CA 94305. E-mail wclusin{at}leland.stanford.edu
Background— Optical mapping of cytosolic calcium transients in intact mammalian hearts is now possible using long-wavelength [Ca2+]i indicators. We propose that beat-to-beat [Ca2+]i transient alternans during ischemia may lead to spatial and temporal heterogeneity of calcium-activated membrane currents.
Methods and Results— To test this hypothesis, isolated rabbit hearts were loaded with the fluorescent [Ca2+]i indicator, rhod-2 AM, and imaged at 300 frames/sec during blood-perfused ischemic trials. High-quality [Ca2+]i transients were recorded in each of 8 hearts.[Ca2+]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 [Ca2+]i transient during the early phase of ischemia, which could produce electrical instability and arrhythmias in large mammalian hearts.
Key Words: calcium • myocardium • ischemia • fluorescence • arrhythmias
This article has been cited by other articles:
 |
|
 |
|
  Y. Xie, A. Garfinkel, J. N. Weiss, and Z. Qu Cardiac alternans induced by fibroblast-myocyte coupling: mechanistic insights from computational models Am J Physiol Heart Circ Physiol, August 1, 2009; 297(2): H775 - H784. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. S. Barth and G. F. Tomaselli Cardiac Metabolism and Arrhythmias Circ Arrhythm Electrophysiol, June 1, 2009; 2(3): 327 - 335. [Full Text] [PDF]
|
|
|
|
|
|
S. Kapur, J. A. Wasserstrom, J. E. Kelly, A. H. Kadish, and G. L. Aistrup Acidosis and ischemia increase cellular Ca2+ transient alternans and repolarization alternans susceptibility in the intact rat heart Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1491 - H1512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. L. Aistrup, Y. Shiferaw, S. Kapur, A. H. Kadish, and J. A. Wasserstrom Mechanisms Underlying the Formation and Dynamics of Subcellular Calcium Alternans in the Intact Rat Heart Circ. Res., March 13, 2009; 104(5): 639 - 649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Wasserstrom, S. Kapur, S. Jones, T. Faruque, R. Sharma, J. E. Kelly, A. Pappas, W. Ho, A. H. Kadish, and G. L. Aistrup Characteristics of intracellular Ca2+ cycling in intact rat heart: a comparison of sex differences Am J Physiol Heart Circ Physiol, November 1, 2008; 295(5): H1895 - H1904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Tang, G.-S. Hwang, H. Hayashi, J. Song, M. Ogawa, K. Kobayashi, B. Joung, H. S. Karagueuzian, P.-S. Chen, and S.-F. Lin Intracellular calcium dynamics at the core of endocardial stationary spiral waves in Langendorff-perfused rabbit hearts Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H297 - H304. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. T. Clusin Mechanisms of calcium transient and action potential alternans in cardiac cells and tissues Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H1 - H10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Warren, J. F. Huizar, A. G. Shvedko, and A. V. Zaitsev Spatiotemporal Relationship Between Intracellular Ca2+ Dynamics and Wave Fragmentation During Ventricular Fibrillation in Isolated Blood-Perfused Pig Hearts Circ. Res., October 26, 2007; 101(9): e90 - e101. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Qu and J. N. Weiss The chicken or the egg? Voltage and calcium dynamics in the heart Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2054 - H2055. [Full Text] [PDF]
|
|
|
|
|
|
J. F. Huizar, M. D. Warren, A. G. Shvedko, J. Kalifa, J. Moreno, S. Mironov, J. Jalife, and A. V. Zaitsev Three distinct phases of VF during global ischemia in the isolated blood-perfused pig heart Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1617 - H1628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Y. Kim, S.-J. Woo, S.-m. Hwang, J. H. Hong, and K. J. Lee Cardiac beat-to-beat alternations driven by unusual spiral waves PNAS, July 10, 2007; 104(28): 11639 - 11642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. E. D. J. ter Keurs and P. A. Boyden Calcium and Arrhythmogenesis Physiol Rev, April 1, 2007; 87(2): 457 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G.-S. Hwang, H. Hayashi, L. Tang, M. Ogawa, H. Hernandez, A. Y. Tan, H. Li, H. S. Karagueuzian, J. N. Weiss, S.-F. Lin, et al. Intracellular Calcium and Vulnerability to Fibrillation and Defibrillation in Langendorff-Perfused Rabbit Ventricles Circulation, December 12, 2006; 114(24): 2595 - 2603. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. L. Aistrup, J. E. Kelly, S. Kapur, M. Kowalczyk, I. Sysman-Wolpin, A. H. Kadish, and J. A. Wasserstrom Pacing-induced Heterogeneities in Intracellular Ca2+ Signaling, Cardiac Alternans, and Ventricular Arrhythmias in Intact Rat Heart Circ. Res., September 29, 2006; 99(7): E65 - E73. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Sato, Y. Shiferaw, A. Garfinkel, J. N. Weiss, Z. Qu, and A. Karma Spatially Discordant Alternans in Cardiac Tissue: Role of Calcium Cycling Circ. Res., September 1, 2006; 99(5): 520 - 527. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. N. Weiss, A. Karma, Y. Shiferaw, P.-S. Chen, A. Garfinkel, and Z. Qu From Pulsus to Pulseless: The Saga of Cardiac Alternans Circ. Res., May 26, 2006; 98(10): 1244 - 1253. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. A. Valverde, C. Mundina-Weilenmann, M. Reyes, E. G. Kranias, A. L. Escobar, and A. Mattiazzi Phospholamban phosphorylation sites enhance the recovery of intracellular Ca2+ after perfusion arrest in isolated, perfused mouse heart Cardiovasc Res, May 1, 2006; 70(2): 335 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Rodriguez-Sinovas, D. Garcia-Dorado, M. Ruiz-Meana, and J. Soler-Soler Protective effect of gap junction uncouplers given during hypoxia against reoxygenation injury in isolated rat hearts Am J Physiol Heart Circ Physiol, February 1, 2006; 290(2): H648 - H656. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. P. Katra and K. R. Laurita Cellular Mechanism of Calcium-Mediated Triggered Activity in the Heart Circ. Res., March 18, 2005; 96(5): 535 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Eisner, M. E. Diaz, Y. Li, S. C. O'Neill, and A. W. Trafford Stability and instability of regulation of intracellular calcium Exp Physiol, January 1, 2005; 90(1): 3 - 12. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. Lakireddy, P. Baweja, A. Syed, G. Bub, M. Boutjdir, and N. El-Sherif Contrasting effects of ischemia on the kinetics of membrane voltage and intracellular calcium transient underlie electrical alternans Am J Physiol Heart Circ Physiol, January 1, 2005; 288(1): H400 - H407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Dworschak, D. Breukelmann, and J. D. Hannon The Impact of Isoflurane During Simulated Ischemia/Reoxygenation on Intracellular Calcium, Contractile Function, and Arrhythmia in Ventricular Myocytes Anesth. Analg., November 1, 2004; 99(5): 1302 - 1307. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Pruvot, R. P. Katra, D. S. Rosenbaum, and K. R. Laurita Role of Calcium Cycling Versus Restitution in the Mechanism of Repolarization Alternans Circ. Res., April 30, 2004; 94(8): 1083 - 1090. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. E. Diaz, S. C. O'Neill, and D. A. Eisner Sarcoplasmic Reticulum Calcium Content Fluctuation Is the Key to Cardiac Alternans Circ. Res., March 19, 2004; 94(5): 650 - 656. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Nearing and R. L. Verrier Tracking cardiac electrical instability by computing interlead heterogeneity of T-wave morphology J Appl Physiol, December 1, 2003; 95(6): 2265 - 2272. [Abstract] [Full Text]
|
|
|
|
|
|
Y.-W. Qian, R. J. Sung, S.-F. Lin, R. Province, and W. T. Clusin Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart Am J Physiol Heart Circ Physiol, December 1, 2003; 285(6): H2722 - H2733. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Stamm, I. Friehs, Y.-H. Choi, D. Zurakowski, F. X McGowan, and P. J del Nido Cytosolic calcium in the ischemic rabbit heart: assessment by pH- and temperature-adjusted rhod-2 spectrofluorometry Cardiovasc Res, September 1, 2003; 59(3): 695 - 704. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. L. Verrier, A. V. Tolat, and M. E. Josephson T-Wave alternans for arrhythmia risk stratification in patients with idiopathic dilated cardiomyopathy J. Am. Coll. Cardiol., June 18, 2003; 41(12): 2225 - 2227. [Full Text] [PDF]
|
|
|
|
 |
|
 L. A Blatter, J. Kockskamper, K. A Sheehan, A. V Zima, J. Huser, and S. L Lipsius Local calcium gradients during excitation-contraction coupling and alternans in atrial myocytes J. Physiol., January 1, 2003; 546(1): 19 - 31. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. D. Nearing and R. L. Verrier Progressive Increases in Complexity of T-Wave Oscillations Herald Ischemia-Induced Ventricular Fibrillation Circ. Res., October 18, 2002; 91(8): 727 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Pieske and J. Kockskamper Alternans Goes Subcellular: A "Disease" of the Ryanodine Receptor? Circ. Res., October 4, 2002; 91(7): 553 - 555. [Full Text] [PDF]
|
|
|
|
|
|
M.E. Diaz, D.A. Eisner, and S.C. O'Neill Depressed Ryanodine Receptor Activity Increases Variability and Duration of the Systolic Ca2+ Transient in Rat Ventricular Myocytes Circ. Res., October 4, 2002; 91(7): 585 - 593. [Abstract] [Full Text] [PDF]
|
|