Abstract 820: Enoxaparin Reverses Ventricular Tachycardia and Torsades de Pointes in Rat Isolated Heart Model

Abstract

Introduction: Enoxaparin (Enox) is used in cardiovascular emergency and coronary angiography due to its effects on coagulation mechanisms. However, its effect on changing the structure of the exchange-inhibiting peptide present in the sodium-calcium exchanger, leading to the acceleration of its function and withdrawing calcium from the cell in overload situations could lead to a new therapeutic function, where the intracellular calcium overload would be deleterious, as in cardiac arrhythmias and myocardial infarction. Objective: To analyze the action of Enox on cardiac arrhythmias induced by ischemia and reperfusion (IR) in isolated rat hearts. Materials and method. Adult Wistar rats were sacrificed, hearts isolated and placed under perfusion in Langhendorf Model with Krebs solution (KS) and monitoring of the electrocardiogram. After 30 minutes in sinus rhythm, ischemia was performed with discontinuation of the KS for 5 min and then reconnected. They were divided into 2 groups: Control (n = 10), with IR without medication and Enox Group, with infusion of 2mg / kg, in the cannula that perfuses the heart, soon after initiation and support for 30 seconds of Ventricular Tachycardia (VT) or Torsade de Pointes (TP). In case of reversal of the arrhythmia, a new arrhythmia induction will be attempted with the same protocol. Monitoring is continued until asystole or completion scheduled for 60 minutes of experimentation. Results: The control group presented VT in 70% of hearts and total atrioventricular block (TAVB) in 30% of hearts, followed by asystole after 7 minutes in 100% of hearts, and no further attempt of ischemia was possible. In the Enox group, 60% of VT, 30% of TP and 10% of TAVB were observed. All arrhythmias were reversed between 10 and 15 seconds after infusion of Enox, with return and maintenance of sinus rhythm after medication. In this group, a new attempt was made to induce arrhythmia due to IR without success after 10 minutes of interruption of the arrhythmia by Enox and sinus rhythm was maintained until the interruption of the experimental protocol. Conclusion: Enoxaparin reverses arrhythmias triggered by IR, with its effect prolonging and protecting new events after infusion, as well as decreasing organ mortality in isolated hearts of rats.

Pharmacological Modulation by Low Molecular Weight Heparin of Purinergic Signaling in Cardiac Cells Prevents Arrhythmia and Lethality Induced by Myocardial Infarction

“…It has also been suggested that this cardioprotective action of ADO mediated by cardiac A1R could occur in different physiological and pathological conditions, including CIR and cardiac pre- and post-ischemic conditioning [ 17 , 18 , 50 , 51 ]. Interestingly, heparin and LMWHs can prevent cardiac arrhythmias associated with sudden death caused by ventricular tachycardia, torsades de pointes , and ventricular fibrillation, and first- and second-degree AVB in animal CIR models, as well as in isolated rat atria [ 17 , 18 , 52 ]. Since Ca 2+ acts as a second intracellular messenger responsible for the regulation of various enzymes in cardiac cells, including AC, intracellular Ca 2+ overload may also indirectly promote myocardial injuries and lethal arrhythmias by disruption of the cardioprotective cAMP–ADO pathway [ 17 ].…”

“…The activation of cardiac β1-AR considerably increases intracellular cAMP levels in cardiac cells when extracellular Ca 2+ is decreased [ 25 , 47 , 53 ] or when the plasmalemmal NCX is inhibited in these cells [ 40 , 52 ]. cAMP, in turn, regulates c[Ca 2+ ] in cardiac cells and its dysfunction plays an important pathological role in the cardiac inflammation induced by AMI [ 27 , 54 ].…”

“…Menezes-Rodrigues et al [ 25 ] and Sassi et al [ 47 ] showed that the blockade of β1-AR in cardiac cells significantly attenuated the negative inotropic effect of extracellular ADO resulting from MRPT-mediated cAMP efflux from muscle cells, thus highlighting the importance of this regulatory mechanism of cardiac function [ 27 , 52 ]. Here, we propose that the antiarrhythmic effects produced by heparins and LMWHs are due to the pharmacological modulation of ADO signaling in cardiac cells.…”