title: The kinetics of spontaneous calcium oscillations and arrhythmogenesis in the in vivo heart during ischemia/reperfusion.
abstract: BACKGROUND
  The correlation between spontaneous calcium oscillations (S-CaOs) and arrhythmogenesis has been investigated in a number of theoretical and experimental in vitro models. There is an obvious lack of studies that directly investigate how the kinetics of S-CaOs correlates with a specific arrhythmia in the in vivo heart.
  
  
  OBJECTIVE
  The purpose of the study is to investigate the correlation between the kinetics of S-CaOs and arrhythmogenesis in the intact heart using an experimental model of ischemia/reperfusion (I/R).
  
  
  METHODS
  Perfused Langendorff guinea pig (GP) hearts were subjected to global I/R (10-15 minutes/10-15 minutes). The heart was stained with a voltage-sensitive dye (RH237) and loaded with a Ca2+ indicator (Rhod-2 AM). Membrane voltage (Vm) and intracellular calcium transient (Ca(i)T) were simultaneously recorded with an optical mapping system of two 16 x 16 photodiode arrays. S-CaOs were considered to arise from a localized focal site within the mapped surface when these preceded the associated membrane depolarizations by 2-15 ms.
  
  
  RESULTS
  In 135 episodes of ventricular arrhythmias from 28 different GP experiments, 23 were linked to S-CaOs that were considered to arise from or close to the mapped epicardial window. Self-limited or sustained S-CaOs had a cycle length of 130-430 ms and could trigger propagated ventricular depolarizations. Self-limited S-CaOs that followed the basic beat action potential (AP)/Ca(i)T closely resembled phase 3 early afterdepolarizations. Fast S-CaOs could remain confined to a localized site (concealed) or exhibit varying conduction patterns. This could manifest as (1) an isolated premature beat (PB), bigeminal, or trigeminal rhythm; (2) ventricular tachycardia (VT) when a regular 2:1 conduction from the focal site develops; or (3) ventricular fibrillation (VF) when a complex conduction pattern results in wave break and reentrant excitation.
  
  
  CONCLUSIONS
  The study examined, for the first time in the intact heart, the correlation between the kinetics of focal S-CaOs during I/R and arrhythmogenesis. S-CaOs may remain concealed or manifest as PBs, VT, or VF. A "benign looking" PB during I/R may represent "the tip of the iceberg" of an underlying potentially serious arrhythmic mechanism.
authors.affiliation: New York Harbor Veterans Administration Healthcare System and State University of New York, Downstate Medical Center, Brooklyn, New York, USA.
authors.forename: Vikram
authors.initials: V
authors.lastname: Lakireddy
authors.forename: Vikram
authors.initials: V
authors.lastname: Lakkireddy
authors.forename: Gil
authors.initials: G
authors.lastname: Bub
authors.forename: Paramdeep
authors.initials: P
authors.lastname: Baweja
authors.forename: Asma
authors.initials: A
authors.lastname: Syed
authors.forename: Mohamed
authors.initials: M
authors.lastname: Boutjdir
authors.forename: Nabil
authors.initials: N
authors.lastname: El-Sherif
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D004195:Disease Models, Animal; D004594:Electrophysiology; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000503:physiopathology; D007700:Kinetics; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000503:physiopathology*; D055095:Optics and Photonics
chemical_list: D002118:Calcium