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. 2013 Aug;10(8):1201-8.
doi: 10.1016/j.hrthm.2013.05.021. Epub 2013 May 29.

Brief endocardial surge of Ca²⁺ transient but monotonic suppression of action potential occurs during acute ischemia in canine ventricular tissue

Takeshi Ueyama  1 , Douglas P Zipes, John C Lopshire, Jiashin Wu
Affiliations

Brief endocardial surge of Ca²⁺ transient but monotonic suppression of action potential occurs during acute ischemia in canine ventricular tissue

Takeshi Ueyama et al. Heart Rhythm. 2013 Aug.

Abstract

Background: Ischemia suppresses action potentials (APs) by elevating interstitial K(+) and activating KATP channels and alters cytosolic Ca(2+) transients (CaTs) via metabolic inhibition.

Objective: To test the hypothesis that AP and CaT respond to ischemia with different spatiotemporal courses and patterns.

Methods: Thirty-four transmural wedges were isolated from canine left ventricular free walls, perfused arterially, and stained with voltage- and Ca(2+)-sensitive dyes. Twenty-eight wedges underwent 15 minutes of arterial occlusion during pacing at a cycle length (PCL) of 300 ms (n = 19) or 600 ms (n = 9). Six other wedges had a sequential reduction of perfusion flow from full to 50%, 25%, and 10% at 300 ms PCL. AP and CaT were recorded on the cut-exposed transmural surfaces with an optical mapping system.

Results: Although ischemia suppressed APs, it enhanced CaT to 150% ± 10% (more in the endocardium than in the epicardium) and induced CaT alternans during the first 2 minutes of arterial occlusion and then suppressed CaT (PCL = 300 ms). Enhancement of CaT (to 159% ± 23%) also occurred during low flow (25%) perfusion (PCL = 300 ms). Faster suppression of AP occurred with subepicardial preference as compared to that of CaT. After 15 minutes of arterial occlusion, AP and CaT remained in only small regions during 300 ms PCL but were preserved in most regions during 600 ms PCL.

Conclusions: Early ischemia induced a surge and alternans in CaT and caused its dissociation from AP both in time course of suppression and in spatial distribution. These results suggested that there were different cellular regulatory mechanisms of AP and of CaT in responding to ischemia from arterial occlusion.

Keywords: AP; Action potential; Acute ischemia; CICR; Ca(2+) transient; Ca(2+)-induced Ca(2+) release; CaT; NCX; Na/Ca exchange; Optical mapping; PCL; SR; action potential; pacing cycle length; sarcoplasmic reticulum.

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