Abstract
BACKGROUND: The effects of anesthetic drugs on myocardial cells have been a subject of research for the last 50 years. The clinical benefits of halogenated agents, particularly sevoflurane, have been demonstrated in cardiac surgery patients. These benefits are due to the action of different enzymes and a variety of molecular pathways mediated by the action of small noncoding RNAs (sRNA) such as microRNAs (miRNAs). However, the modulation potential induced by anesthetic drugs on the miRNA expression and their cardioprotective effects is unknown. OBJECTIVE: To analyze the variation in the expression of a panel of miRNAs induced by halogenated agents to identify their cardioprotective effects. AIMS: Variations in the expression of specific miRNAs induce the potential cardioprotective effects of halogenated agents. METHODS: An ischemia/reperfusion (I/R) in vitro model of primary human cardiac myocytes (HCMs) was performed. Four study groups were performed: control group (standard culture conditions), I/R group (without hypnotic drugs exposition), I/R-propofol group (I/R-P), and I/R-sevoflurane group (I/R-S). The secretion of p53 and Akt1 cytokines was quantified in the different cell study groups using an Enzyme-Linked ImmunoSorbent Assay, and the differentially expressed miRNAs were identified carrying out a complete genomic sequencing using the Next Generation Sequencing (NGS). RESULTS: HCMs subjected to the I/R procedure and exposed to sevoflurane showed lower secretion levels of p53 factor and higher levels of Akt-1 cytokine compared to HCMs exposed to propofol (p53: I/R-S: 10.43 ± 0.91 ng/mL; I/R-P: 137.92 ± 7.53 ng/mL; p > 0.05); (Akt1: I/R-S: 0.62 ± 0.12 ng/mL; I/R-P: 0.23 ± 0.05 ng/mL; p > 0.05). The miRNA gene expression analysis (NGS) showed significantly increased expression of the hsa-miR-140-5p and hsa-miR-455-5p, both miRNAs associated with cardiac function; the hsa-miR-98-5p and hsa-miR-193a-5p, both related to apoptosis inhibition; and the hsa-let-7d-5p associated with myocardial protection. This increase was observed in the HCMs group exposed to sevoflurane in comparison to the propofol group. CONCLUSIONS: Sevoflurane-induced miRNAs overexpression confers cardioprotection through various mechanisms at the DNA level and the different signaling pathways levels, such as Akt/ERK.