# Cardioprotective effects of the ranolazine in myocardial infarction mediated by stimulation of the endogenous mediators involved in ischemic preconditioning

## TL;DR

Ranolazine protects the heart during infarction by activating natural protective pathways similar to those used in ischemic preconditioning.

## Contribution

This study shows ranolazine mimics ischemic preconditioning by using endogenous mediators like nitric oxide and ATP-dependent potassium channels.

## Key findings

- Ranolazine reduced infarct size and cardiac enzyme levels similar to ischemic preconditioning.
- Blocking nitric oxide and ATP channels reversed ranolazine's protective effects.
- Ranolazine could serve as a non-surgical alternative to ischemic preconditioning in heart procedures.

## Abstract

Hypothesis centered on the idea that ranolazine could induce responses similar to ischemic preconditioning, involving nitric oxide, adenosine, bradykinin, and adenosine triphosphate (ATP)-dependent potassium channels.

Ischemia-reperfusion injury was established using Langendroff technique. Thirty-minute ischemia and 120-minute reperfusion to coronary artery to isolated heart were model of myocardial infarction. There were studied the following groups: control (ischemia-reperfusion), ischemic preconditioning, ranolazine (10 µmol/L), ranolazine + L-NAME (30 µmol/L) and ranolazine + aminoguanidine (30 µmol/L), ranolazine + theophylline (50 µmol/L), ranolazine + aminophylline (50 µmol/L), ranolazine + icatibantl (100 µmol/L), ranolazine + bromelain (250 µmol/L), ranolazine + 5-hydroxydecanoate (30 µmol/L), and ranolazine + glimepiride (50 µmol/L) in perfusate.

Ranolazine and ischemic preconditioning groups demonstrated cardioprotective effects by reducing infarct size, as well as levels of lactate dehydrogenase (LDH), creatine phosphokinase myoglobin (CK-MB), and troponin I and cardiac parameters like left ventricular developed pressure (LVDP) and left ventricular maximum rate of contraction (dP/dTmax). Maximum rate of relaxation (dP/dTmin) was improved. Conversely, treatments with L-NAME, aminoguanidine, theophylline, aminophylline, icatibant, bromelain, 5-hydroxydecanoate, and glimepiride increased infarct size, LDH, CK-MB, and troponin I levels, and cardiac parameters like LVDP, dP/dTmax, and dP/dTmin were depressed. This data provides evidence that ranolazine employs nitric oxide, adenosine, bradykinin, and ATP-dependent potassium channels as secondary messengers in cardioprotection.

ranolazine can be a pharmacological alternative to surgical ischemic preconditioning utilized prior to interventional procedures like coronary artery bypass graft surgery and heart transplantation, offering improved patient compliance.