Effect of high intensity ultrasound pulses and microbubbles (Sonothrombolysis) on autonomic modulation, cardiac function and intracellular signaling after ST - elevation Myocardial Infarction

• Grant number: 18/01325-4
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Effective date (Start): July 01, 2018
• Effective date (End): June 30, 2022
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Wilson Mathias Júnior
• Grantee: Luciene Ferreira Azevedo
• Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
• Associated research grant: 18/06387-8 - High ultrasound mechanical index and microbubbles to reduce acute myocardial infarction burden I. HUBBLE-I study, AP.TEM

Abstract

The Acute Myocardial Infarction (AMI), which may be the first manifestation of Coronary Arterial Disease (CAD) or may occur in patients with established disease, was indicated by Datasus as the first cause of death in the country, with a record of approximately 100 thousand annual deaths. AMI causes dysfunction of the autonomic nervous system, characterized by cardiac and periphery autonomic imbalance, with predominance of sympathetic modulation. This sympathetic hyperactivation, which acutely can be beneficial, may cause deleterious effects to the heart, culminating in loss of left ventricular function and heart failure. In addition, the sympathetic hyperactivation impairs neurovascular control and endothelial dilating function. If, on the one hand, AMI has a deleterious effect on the ANS balance, affecting cardiac function, cardiac baroreflex sensitivity and endothelial function; on the other hand, high-energy ultrasound with microbubbles (sonothrombolysis), previously applied to percutaneous coronary intervention, proved to be effective for the recanalization of coronary arteries, leading to reperfusion and restoration of coronary vascular and microvascular flow and ventricular function in post-AMI patients. One of the candidate mechanisms for increased coronary microvascular flow observed after sonothrombolysis is increased nitric oxide release caused by shear stress from cavitation of the microbubbles in the vessel wall. Recent studies demonstrate that nitric oxide activity appears to be regulated by circulating micro RNAs (ci-miRNAs) and specific RNAs have been linked to vascular function because they are elevated when endothelial cells undergo shear stress and may thus play an important role in angiogenesis, as regulators of the proangiogenic protein VEGF (vascular endothelial growth factor). These ci-miRNAs may be strong candidates to help explain the mechanism of increase in coronary microcirculation following sonothrombolysis and its favourable repercussion on cardiac dysfunction after AMI. The results of this new therapy for the early treatment of AMI are promising; however, its effect on the sympathetic hyperactivation after AMI and the deleterious effect of this autonomic myocardial alteration is still unknown and deserves to be investigated. In this context, we aimed to investigate the effect of sonothrombolysis on cardiac sympathetic hyperactivation, cardiac and vascular autonomic modulation, baroreflex sensitivity, cardiac function and ci-miRNA levels in the 6-months course after AMI with ST segment elevation. (AU)