Abstract
BackgroundHypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, however, the effect of miRNAs on the progression of hypothermic ischemic–reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored.MethodsSprague-Dawley (SD) rats were randomly divided into two groups (n = 8): a normal control group (Group C) and a hypothermic ischemia-reperfusion group (Group IR), which were used to establish a Langendorff isolated cardiac perfusion model. According to the arrhythmia scoring system, rats in group IR were divided into a high-risk group (IR-H) and a low-risk group (IR-L). miRNAs expression profiles of ventricular myocardium with global hypothermic ischemia–reperfusion and those of ventricular myocardium with hypothermic ischemia–RA were established through high-throughput sequencing. Furthermore, the aberrantly expressed miRNAs in myocardium with and without hypothermic ischemia–RA were screened and verified. The target genes of these aberrantly expressed miRNAs were predicted using RNAhybrid and MiRanda software. Based on Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, we determined the mRNA targets associated with these miRNAs and studied the miRNA–mRNA interaction during the cardiovascular disease progression. The aberrantly expressed miRNAs related to hypothermic ischemia–RA were validated by Real-time Quantitative polymerase chain reaction (RT-qPCR).ResultsEight significantly aberrantly expressed miRNAs (rno-miR-122-5p, rno-miR-429, novel_miR-1, novel_miR-16, novel_miR-17, novel_miR-19, novel_miR-30, and novel_miR-43) were identified, among which six were up-regulated and two were down-regulated. Moreover, target genes and signaling pathways associated with these aberrantly expressed miRNAs were predicted and analyzed. The miRNA–mRNA interaction network graph showed that GJA1 gene was considered as the target of novel_miR-17.ConclusionsAberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–RA. Specific miRNAs, such as novel_miR-17 and rno-miR-429 are probably new potential targets for further functional studies of hypothermic ischemia–RA.
Highlights
Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass
Aberrantly expressed miRNAs were possibly associated with the formation mechanism of hypothermic ischemia–reperfusion arrhythmias (RA)
With the development of various technologies such as anesthesia and cardiopulmonary bypass (CPB), the effect of cardiac surgical procedures has been greatly improved, RA remains the major complication during heart resuscitation through open heart surgery under CPB, which directly influences whether the surgery can be successfully conducted or not and patient prognosis
Summary
Hypothermic ischemia-reperfusion arrhythmia remains the main factor affecting cardiac resuscitation under cardiopulmonary bypass. Existing research shows that certain miRNAs exhibit significantly different expressions and effects in arrhythmias, the effect of miRNAs on the progression of hypothermic ischemic– reperfusion arrhythmias (RA) and its potential mechanism remain to be further explored. RA is one of characteristics of myocardial ischemia–reperfusion injury (MIRI). It mainly appears as various ventricular arrhythmias including ventricular premature beat, ventricular tachycardia (VT), and ventricular fibrillation. With the development of various technologies such as anesthesia and cardiopulmonary bypass (CPB), the effect of cardiac surgical procedures has been greatly improved, RA remains the major complication during heart resuscitation through open heart surgery under CPB, which directly influences whether the surgery can be successfully conducted or not and patient prognosis. Investigating the mechanism of formation of RA after hypothermic ischemia is important when trying to prevent these kinds of complications and provides new targets and directions for clinical treatment
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