Heparin Oligosaccharides Have Antiarrhythmic Effect by Accelerating the Sodium-Calcium Exchanger

Figures

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  Scheme 1. Diagram of the experimental protocol for each route of drug administration in the rat. IV: intravenous.

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  Figure 1. Typical electrogram records of isolated rat atria submitted to the electric field stimulation (EFS) protocol. The effect of the EFS-protocol on atrial response was studied in the absence of any drug treatment (control, Left upper) as well as in the presence of 50 μM KB-R7943 alone (Right upper), 10 μM enoxaparin alone (Left lower) and the simultaneous presence of 50 μM KB-R7943 and 10 μM enoxaparin (Right lower). The sinus rates (Hz) prior to the EFS-protocol were 3.7, 3.6, 0.9, and 1.2 in control, enoxaparin alone, KB-R7943 alone and enoxaparin + KB-R 7043 groups, respectively. Accordingly, the atrial rates (Hz) following the EFS-protocol for these groups were 25, 5.8, 25, and 25, respectively.

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  Figure 2. (A,B) Calcium transients induced by Bay-K in either the absence (control) or presence of enoxaparin (ENOX 1 μM) or ardeparin (ARD 1 μM). (C) Calcium transient induced by Bay-K in the presence of either nifedipine alone (NIF 1 μM) or simultaneous presence of 1 μM NIF and 1 μM ENOX. (D,E) Calcium transients induced by the caffeine-ryanodine-thapsgargin cocktail (CRT) in either the absence (control) or presence of 1 μM ENOX or 1 μM ARD.

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  Figure 3. Effects of trisulfated heparin disaccharide (TD) on the NCX current (NCX) recorded from acutely isolated rat ventricular myocytes at various Cai (A: 300 nM; B: 400 nM and C: 600 nM). The graph (D) is % change obtained by dividing the current amplitude value at a given voltage for a given test compound concentration by the current value recorded in the absence of test compound (control).