Photobiomodulation therapy combined with carvedilol attenuates post-infarction heart failure by suppressing excessive inflammation and oxidative stress in rats

Vanessa Grandinetti,Gianna Móes Albuquerque-Pontes,Luis Felipe Neves Dos Santos,Ernesto Cesar Leal-Junior,Flávio André Silva,Paulo José Ferreira Tucci,Fernando Pereira Carlos,Helenita Antonia De Oliveira,Paulo De Tarso Camillo De Carvalho,Amanda Yoshizaki,Barbara Sampaio Dias Martins Mansano,Andrey Jorge Serra,Leslie Andrews Porte,Martha Trindade Manchini,Ednei Luiz Antonio

doi:10.1038/s41598-019-46021-1

Abstract

The post-myocardial infarction heart failure (HF) still carries a huge burden since current therapy is unsuccessful to abrogate poor prognosis. Thus, new approaches are needed, and photobiomodulation therapy (PBMt) may be a way. However, it is not known whether PBMt added to a standard HF therapy provides additional improvement in cardiac remodeling in infarcted rats. This study sought to determine the combined carvedilol-drug and PBMt with low-level laser therapy value in HF. Rats with large infarcts were treated for 30 days. The functional fitness was evaluated using a motorized treadmill. Echocardiography and hemodynamic measurements were used for functional evaluations of left ventricular (LV). ELISA, Western blot and biochemical assays were used to evaluate inflammation and oxidative stress in the myocardium. Carvedilol and PBMt had a similar action in normalizing pulmonary congestion and LV end-diastolic pressure, attenuating LV dilation, and improving LV systolic function. Moreover, the application of PBMt to carvedilol-treated rats inhibited myocardial hypertrophy and improved +dP/dt of LV. PBMt alone prevented inflammation with a superior effect than carvedilol. Carvedilol and PBMt normalized 4-hydroxynonenal (a lipoperoxidation marker) levels in the myocardium. However, importantly, the addition of PBMt to carvedilol attenuated oxidized protein content and triggered a high activity of the anti-oxidant catalase enzyme. In conclusion, these data show that the use of PBMt plus carvedilol therapy results in a significant additional improvement in HF in a rat model of myocardial infarction. These beneficial effects were observed to be due, at least in part, to decreased myocardial inflammation and oxidative stress.

Highlights

The post-myocardial infarction heart failure (HF) still carries a huge burden since current therapy is unsuccessful to abrogate poor prognosis
Pulmonary congestion was reduced with therapies (Fig. 1B), and the MICL group had a normalized left ventricular (LV) mass/ body weight ratio (Fig. 1C)
On LV hemodynamic examination, heart rate was similar between groups, but there was a reduction in LV pressure in all infarcted rats (Fig. 2E,F)

Summary

Introduction

The post-myocardial infarction heart failure (HF) still carries a huge burden since current therapy is unsuccessful to abrogate poor prognosis. The addition of PBMt to carvedilol attenuated oxidized protein content and triggered a high activity of the anti-oxidant catalase enzyme These data show that the use of PBMt plus carvedilol therapy results in a significant additional improvement in HF in a rat model of myocardial infarction. These beneficial effects were observed to be due, at least in part, to decreased myocardial inflammation and oxidative stress. We and other researcher groups have demonstrated a smaller myocardial injury and attenuated left ventricular (LV) dysfunction in rats submitted to photobiomodulation therapy (PBMt)[4,5,6] These data are stimulating, there are unclear issues that must be resolved prior to a clinical trial. Carvedilol and PBMt have an analogous effect on inflammation and oxidative stress[7,8,9,10,11], in which it could lead to a hypothesis of the synergistic effect

Methods

Results

Conclusion