Neurotransmissão colinérgica na isquemia miocárdica aguda em ratos

Abstract

Acute myocardial infarction is the major natural death cause in the world, killing millions of people every year. Despite of several major therapeutic advances in the last few decades, the life-threatening cardiac arrhythmias in initial hyper-acute phase of myocardial infarction remains as an important cause of death in infarcted patients. Therefore, the intensive search for new therapeutic strategies is still necessary. Since in this hyper-acute phase of myocardial infarction, cardiac autonomic imbalance contributes to the pathogenesis of cardiac arrhythmias, new therapeutic strategies based on autonomic modifications seems to be justifiable. In the present study, cardiac vagal cholinergic neurotransmission potentiation induced by an anti-cholinesterasic agent, pyridostigmine bromide, was investigated in anesthetized rats with myocardial infarction, which was induced via occlusion of anterior descendent left coronary artery. This occlusion provokes an extensive anterior-lateral myocardial infarction associated with several life-threatening ventricular arrhythmias and elevated mortality. The present study demonstrates for the first time that endovenous injection of repeated bolus of pyridostigmine bromide (at doses varying from 0,3mg/Kg to 0,6mg/Kg) promotes myocardial protection, significantly reducing the score of complex ventricular arrhythmias, with a major trend to prolong survival rate in the animals during the first four hours of myocardial infarction. These effects were accompanied with an immediate mild to moderate sinusal bradycardia associated with mild systemic arterial hypotension after two hours of treatment. The pyridostigmine bromide treatment did not change the size of myocardial infarction, quantified via ex vivo perfusion of whole heart with Evans’blue stain or in myocardial slices incubated with triphenyltetrazoliun chloride. Even though the possible molecular mechanisms of these effects have not been explored in the present study, these results confirm and widen previous data, opening a huge perspective of a future possible clinical use of pyridostigmine bromide as an adjuvant therapy in the treatment of acute myocardial infarction in human beings.