Mechanisms of shock-induced arrhythmogenesis during acute global ischemia

Abstract

Little is known about the mechanisms of vulnerability and defibrillation under ischemic conditions. We investigated these mechanisms in 18 Langendorff-perfused rabbit hearts during 75% reduced-flow ischemia. Electrical activity was optically mapped from the anterior epicardium during right ventricular shocks applied at various phases of the cardiac cycle while the excitation-contraction decoupler 2,3-butanedione monoxime (BDM; 15 mM) was used to suppress motion artifacts caused by contraction of the heart. During ischemia, vulnerable window width increased [from 30-90% of the action potential duration (APD) in the control to -10 to 100% of the APD in ischemia]. Moreover, arrhythmia severity increased along with the reduction of APD (176 +/- 9 ms in control and 129 +/- 26 ms in ischemia, P < 0.01) and increased dispersion of repolarization (45 +/- 17 ms in control and 73 +/- 28 ms in ischemia, P < 0.01). Shock-induced virtual electrode polarization was preserved. Depolarizing (contrary to hyperpolarizing) response time constants increased. Virtual electrode-induced wavefronts of excitation had much more tortuous pathways leading to wavefront fractionation. Defibrillation failure at all shock strengths was observed in four hearts. Optical mapping revealed that the shock extinguished the arrhythmia; however, the arrhythmia self-originated after an isoelectric window of 339 +/- 189 ms. In conclusion, in most cases, virtual electrode-induced phase singularity (VEIPS) was responsible for shock-induced arrhythmogenesis during acute global ischemia. Enhancement of arrhythmogenesis was associated with an increased dispersion of repolarization and altered deexcitation. In four hearts, arrhythmogenesis could not be explained by VEIPS.

Effets cardioprotecteurs du propofol dans des cœurs ischémiques puis reperfusés isolés chez le cobaye: rôle des canaux KATP et du GSK GSK-3β

“…Several studies using optical mapping have demonstrated that APD is shortened during low flow ischemia. [27][28][29] However, in the current study, we induced global ischemia. Under these experimental conditions, our high resolution imaging device detected only weak change in fluorescence, therefore, we could not record the APD during ischemia.…”

Spatial heterogeneity of action potential alternans during global ischemia in the rabbit heart

“…Motion blockers were avoided because they might prevent alternans from being observed. Two laboratories have used di-4-ANEPPS to study defibrillation mechanisms in ischemic hearts treated with DAM (4,13,15). Ischemia still Fig.…”

“…Fluorescence imaging has been used to map Ca 2ϩ transient alternans during ischemia in the blood-perfused rabbit heart (30), and marked spatial heterogeneity was found. Optical methods have also been used to study the mechanism of electrical defibrillation in the presence and absence of ischemia in hearts taken from small mammals (4,13,15). For these studies, fully intact hearts were used, which were stained with di-4-ANEPPS and treated with the pharmacological motion blocker diacetyl monoxime (DAM).…”

Mechanisms of superiority of ascending ramp waveforms: new insights into mechanisms of shock-induced vulnerability and defibrillation

“…We compared the gradient of VEP (ٌVEP) at the end of the shock and the postshock conduction velocity (vc) between AR and DR waveforms. On the basis of our previous study (5), the total number of pixels with ٌVEP larger than 24 mV/mm was defined as the index of ٌVEP (NVEP), which served as a quantitative measure of ٌVEP generated by the shocks. Postshock vc was calculated from the maps of activation using a previously described algorithm (31).…”

“…Rabbit hearts (n ϭ 10) were Langendorff perfused, and AR and DR waveforms (7,20, and 40 ms) were randomly delivered from two line electrodes placed 10 mm apart on the anterior ventricular epicardium. We optically mapped cellular responses to shocks of various strengths (5,10, and 20 V/cm) and coupling intervals (CIs; 120, 180, and 300 ms). Optical mapping revealed that maximum virtual electrode polarization (VEP) was reached at significantly different times for AR and DR of the same duration (P Ͻ 0.05) for all tested CIs.…”