Simulated regional ischemia in neonatal rat ventricular myocyte monolayers caused progressive conduction velocity slowing and spontaneous reentry in 5 of 11 monolayers.
Does acute regional ischemia/reperfusion alter electrophysiology and promote arrhythmias in neonatal rat ventricular myocyte monolayers?
Acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers recapitulates electrophysiological alterations and arrhythmias seen in intact hearts, with slow recovery of connexin-43 dephosphorylation leading to persistent conduction velocity slowing and arrhythmogenesis during early reperfusion.
BACKGROUND: Electrophysiological changes promoting arrhythmias during acute regional ischemia/reperfusion are challenging to study in intact cardiac tissue because of complex 3-dimensional myocardial and vascular geometry. We characterized electrophysiological alterations and arrhythmias during regional ischemia/reperfusion in a simpler 2-dimensional geometry of cultured neonatal rat ventricular myocyte monolayers. METHODS AND RESULTS: Optical mapping of intracellular Ca (Ca(i)) and voltage was performed with the use of Rhod 2-AM and Rh-237, respectively. Regional ischemia was mimicked by covering the central portion of monolayer with a glass coverslip, and reperfusion was mimicked by removing the coverslip. Monolayers were stained with fluorescent antibodies to detect total and dephosphorylated connexin-43 at various time points. During coverslip ischemia, action potential duration shortened, Ca(i) transient duration was prolonged, and local conduction velocity (CV) slowed progressively, with loss of excitability after 10.6 +/- 3.6 minutes. CV slowing was accompanied by connexin-43 dephosphorylation. During ischemia, spontaneous reentry occurred in 5 of 11 monolayers, initiated by extrasystoles arising from the border zone or unidirectional conduction block of paced beats. On reperfusion, excitability recovered within 1.0 +/- 0.8 minutes, but CV remained depressed for 9.0 +/- 3.0 minutes, promoting reentry in the reperfused zone. As connexin-43 phosphorylation recovered in the reperfused zone, CV normalized, and arrhythmias resolved. CONCLUSIONS: Acute regional ischemia/reperfusion in neonatal rat ventricular myocyte monolayers recapitulates electrophysiological alterations and arrhythmias similar to those observed during acute coronary occlusion/reperfusion in intact hearts. During early reperfusion, slow recovery from connexin-43 dephosphorylation leads to persistent CV slowing, creating a highly arrhythmogenic substrate.
Diego et al. (Tue,) conducted a other in Acute regional ischemia/reperfusion (n=11). Simulated regional ischemia/reperfusion vs. Baseline/normal conditions was evaluated on Electrophysiological alterations and arrhythmias (conduction velocity, excitability, reentry). Simulated regional ischemia in neonatal rat ventricular myocyte monolayers caused progressive conduction velocity slowing and spontaneous reentry in 5 of 11 monolayers.
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