Protective effect of JTV519, a new 1,4-benzothiazepine derivative, on prolonged myocardial preservation

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In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model
08:22

In vitro Assessment of Myocardial Protection following Hypothermia-Preconditioning in a Human Cardiac Myocytes Model

Published on: October 27, 2020

M Hachida1, S Kihara, M Nonoyama

  • 1Department of Cardiovascular Surgery, The Heart Institute of Japan, Tokyo Women's Medical College, Shinjuku. shachida@hij.twmc.ac.jp

Journal of Cardiac Surgery
|May 2, 2000
PubMed
Abstract

Insights

JTV519 protects heart muscle from damage during prolonged ischemia by reducing intracellular calcium overload. This compound demonstrated significant benefits compared to standard cardioplegia, offering a promising adjunct for myocardial protection.

Area of Science:

  • Cardiology
  • Cardiovascular Research
  • Pharmacology

Background:

  • JTV519 is known to protect cardiomyocytes from calcium overload.
  • Myocardial ischemia can lead to significant cellular damage.
  • Diltiazem, a 1,5-benzothiazepine derivative, is a comparator drug.

Purpose of the Study:

  • To investigate the protective effect of JTV519 on myocardium subjected to prolonged ischemia.
  • To elucidate the mechanism underlying JTV519's protective action.
  • To compare JTV519's efficacy with diltiazem.

Main Methods:

  • Isolated rat hearts were divided into three groups: control, JTV519, and diltiazem.
  • Hearts underwent cardiac arrest using histidine-tryptophan-ketoglutarat (HTK) cardioplegic solution with or without JTV519 or diltiazem.
  • All hearts were stored for 6 hours at 4°C in HTK solution.

Main Results:

  • JTV519 and diltiazem significantly improved left ventricular developed pressure post-reperfusion compared to controls.
  • The JTV519 group showed lower left ventricular end-diastolic pressure and better coronary flow recovery.
  • Intracellular calcium concentration was attenuated by JTV519 and diltiazem.

Conclusions:

  • JTV519 demonstrates significant myocardial protection when used as an adjunct to cardioplegia during 6-hour ischemia.
  • JTV519's protective benefits are linked to its inhibition of post-ischemic intracellular calcium increase.
  • JTV519 represents a potential therapeutic strategy for myocardial protection in ischemic conditions.

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