Transmembrane Potentials During High Voltage Shocks in Ischemic Cardiac Tissue

Abstract

Transmembrane, voltage sensitive fluorescent dye (TMF) recording techniques have shown that high voltage shocks (HVS), typically used in defibrillation, produce either hyper- or depolarization of the transmembrane potential (TMP) when delivered in the refractory period of an action potential (AP) in normal cardiac tissue (NT). Further, HVS produce an extension of the AP, which has been hypothesized as a potential mechanism for electrical defibrillation. We examined whether HVS modify TMP of ischemic tissue (IT) in a similar manner. In seven Langendorff rabbit hearts, recordings of APs were obtained in both NT and IT with TMF using di-4-ANEPPS, and diacetylmonoxime (23 microM) to avoid motion artifacts. Local ischemia was produced by occlusion of the LAD, HVS of either biphasic (5 + 5 ms) or (3 + 2 ms) or monophasic shapes (5 ms) were delivered at varying times (20%-90%) of the paced AP. Intracardiac ECG and TMF recordings of the TMP were each amplified, recorded, and digitized at a frequency of 1 kHz. The paced AP in IT was triangular in shape with no obvious phase 3 plateau, typically seen in NT. There was normally a reduced AP amplitude (expressed as fractional fluorescence) in IT (2.6% +/- 1.79%) compared to 3.8% +/- 0.66% in NT, and shortened AP duration (137 +/- 42 vs 171 +/- 11 ms). One hundred-Volt HVS delivered during the refractory period of paced AP in IT in five rabbits, elicited a depolarization response of the TMP with an amplitude up to three times greater than the paced AP. This is in contrast to NT where the 100-V HVS produced hyperpolarization in four hearts, and only a slight depolarization response in one heart. These results suggest that HVS, typically delivered by a defibrillation shock, modify TMPs in a significantly different manner for ischemic cells, which may influence success in defibrillation.

Measurements of Electrophysiological Effects of Components of Acute Ischemia in Langendorff‐Perfused Rat Hearts Using Voltage‐Sensitive Dye Mapping

“…As shown by the mathematical modeling studies of Shaw and Rudy, 42,43 this is expected to result in a significant shortening of the action potential without appreciably affecting conduction velocity. Shortening of APD in response to ischemia has also been demonstrated in several studies using optical mapping in species other than the rat 2–4,7 . Most of these studies used either BDM as a motion blocker, or no motion blocker, 3 although the recent study of Liu et al used cyto‐D in rabbit hearts.…”

“…These methods have many advantages, including high spatial and temporal resolution, direct recording of transmembrane (as opposed to extracellular) potential, and the absence of artifacts caused by electrical stimulation 1 . A large number of studies of cardiac arrhythmias using optical mapping have been published, including several that specifically address arrhythmias arising in the context of ischemia 2–8 . One of the most significant limitations of optical mapping techniques to date is the presence of “motion artifacts” (artifactual signals caused by the contraction of the heart muscle).…”

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).…”

Impact of Myocardial Ischemia and Reperfusion on Ventricular Defibrillation Patterns, Energy Requirements, and Detection of Recovery

“…It is also possible that ischemic tissue is more vulnerable to the effects of strong shocks. 15 If so, strong defibrillation shocks delivered during acute ischemia or reperfusion may contribute to the reinitiation of VF after an interval of postshock organized rhythm, leading to defibrillation failure and delayed VF recurrence. However, the lack of correlation between shock strength and VF recurrence time ( Figure 6) and the substantial fractions of occlusion (4 of 12) and reperfusion VF episodes (4 of 18) defibrillated by shocks Ͼ1.5ϫE-DFT energy level do not support this scenario.…”