Search

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. Objectives: 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 (CaiT) were simultaneously recorded with an optical mapping system of two 16 × 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)/CaiT 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. [Copyright &y& Elsevier]

Repolarization alternans has been considered a strong marker of electrical instability. The objective of this study was to investigate the hypothesis that ischemia-induced contrasting effects on the kinetics of membrane voltage and intracellular calcium transient (CaiT) can explain the vulnerability of the ischemic heart to repolarization alternans. Ischemia-induced changes in action potential (AP) and CaiT resulting in alternans were investigated in perfused Langendorff guinea pig hearts subjected to 10–15 min of global no-flow ischemia followed by 10–15 min of reperfusion. The heart was stained with 100 μl of rhod-2 AM and 25 μl of RH-237, and AP and CaiT were simultaneously recorded with an optical mapping system of two 16 × 16 photodiode arrays. Ischemia was associated with shortening of AP duration (D) but delayed upstroke, broadening of peak, and slowed decay of CaiT resulting in a significant increase of CaiT-D. The changes in APD were spatially heterogeneous in contrast to a more spatially homogeneous lengthening of CaiT-D. CaiT alternans could be consistently induced with the introduction of a shorter cycle when the upstroke of the AP occurred before complete relaxation of the previous CaiT and generated a reduced CaiT. However, alternans of CaiT was not necessarily associated with alternans of APD, and this was correlated with the degree of spatially heterogeneous shortening of APD. Sites with less shortening of APD developed alternans of both CaiT and APD, whereas sites with greater shortening of APD could develop a similar degree of CaiT alternans but slight or no APD alternans. This resulted in significant spatial dispersion of APD. The study shows that the contrasting effects of ischemia on the duration of AP and CaiT anad, in particular, on their spatial distribution explain the vulnerability of ischemic heart to alternans and the increased dispersion of repolarization during alternans. [ABSTRACT FROM AUTHOR]