Pyridostigmine improves post-resuscitation myocardial dysfunction in a rat model of ventricular fibrillation-induced cardiac arrest and resuscitation

Eur J Pharmacol. 2025 Sep 15:1003:177917. doi: 10.1016/j.ejphar.2025.177917. Epub 2025 Jul 10.

Abstract

Background: Post-resuscitation myocardial dysfunction is one of the major causes of death in post-cardiac arrest patients. Pyridostigmine (PYR) shows protective effects on myocardial ischemia-reperfusion injury following myocardial infarction and left heart failure by improving autonomic nervous function. This study aimed to investigate the effects of low-dose pyridostigmine on post-resuscitation myocardial dysfunction.

Methods and results: A rat model of cardiac arrest and resuscitation was induced by ventricular fibrillation (VF). The rats were randomly categorised into the following four groups: control (Con), Control + PYR (Con-PYR), Cardiac arrest (CA), and Cardiac arrest + PYR (CA-PYR) groups. PYR was administered to rats at 0.25 mg/kg before VF induction by intraperitoneal injection. At 24 h after return of spontaneous circulation (ROSC), echocardiography, heart rate variability, and invasive haemodynamics were measured. Blood and heart tissue samples were collected for further analysis. PYR improved the hypoxic state in the rat model of cardiac arrest and resuscitation. It significantly improved left ventricular systolic function and hemodynamics compared with the CA group. Additionally, it reduced myocardial injury, improved mitochondrial dysfunction, and decreased myocardial inflammation and apoptosis in the rat model of cardiac arrest and resuscitation. It reduced the left ventricular protein expression of muscarinic acetylcholine type 2-receptor, increased power spectral analysis of heart rate variability, and partially restored autonomic nervous function in this rat model.

Conclusions: Low-dose PYR improved autonomic nervous function, reduced myocardial injury and inflammation, and improved cardiac dysfunction in rat model of cardiac arrest and resuscitation.

Keywords: Autonomic nervous function; Cardiac arrest; Post-resuscitation myocardial dysfunction; Pyridostigmine.

MeSH terms

  • Animals
  • Apoptosis / drug effects
  • Cardiopulmonary Resuscitation* / adverse effects
  • Disease Models, Animal
  • Heart Arrest* / drug therapy
  • Heart Arrest* / etiology
  • Heart Arrest* / physiopathology
  • Hemodynamics / drug effects
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Pyridostigmine Bromide* / pharmacology
  • Pyridostigmine Bromide* / therapeutic use
  • Rats
  • Rats, Sprague-Dawley
  • Ventricular Fibrillation* / complications
  • Ventricular Fibrillation* / physiopathology

Substances

  • Pyridostigmine Bromide