Optical mapping of V m and Cai2+ in a model of arrhythmias induced by local catecholamine application in patterned cell cultures

Academic Article

Abstract

  • Catecholamines are known to provoke cardiac arrhythmias, but important aspects such as localization of the arrhythmia source in multicellular tissue and exact ionic mechanisms are not well-known. In this work, a multicellular model of arrhythmias caused by local epinephrine application was developed; V m and Cai2+ changes at the arrhythmia source were measured using fluorescent dyes and high-resolution optical mapping. Cultured strands of neonatal rat myocytes (width ∼0.4 mm) were produced by patterned growth. Epinephrine (1 μmol/l) was applied over an area of 0.3-0.6 mm via two micropipettes, and strands were stimulated by burst pacing. Local epinephrine application caused triggered arrhythmias with cycle lengths of 202-379 ms and duration of >10 s in 9 out of 16 preparations. Optical V m mapping demonstrated that in 78% of cases, the source of arrhythmia was located at the boundary of the locally perfused area. Staining with Ca i2+-sensitive dye Fluo-4 prevented arrhythmia induction in most cases (85%) likely due to Ca2+ buffering by the dye. Optical Cai2+ mapping revealed non-propagated Cai2+ oscillations at the boundary of the locally perfused area in 45% cases. In conclusion, we developed a new model of catecholamine-dependent arrhythmias allowing mapping of V m and Cai2+ at the arrhythmia source with microscopic resolution. The arrhythmias typically originated from the boundary of the epinephrine-perfused area. The location of the arrhythmia source correlated with localized Cai2+ oscillations suggesting that arrhythmias were caused by Cai2+ overload at these locations. © 2006 Springer-Verlag.
  • Digital Object Identifier (doi)

    Author List

  • Lan DZ; Pollard AE; Knisley SB; Fast VG
  • Start Page

  • 871
  • End Page

  • 877
  • Volume

  • 453
  • Issue

  • 6