scholarly journals Identifying lncRNA- and Transcription Factor-Associated Regulatory Networks in the Cortex of Rats With Deep Hypothermic Circulatory Arrest

2021 ◽  
Vol 12 ◽  
Author(s):  
Mengya Liang ◽  
Yi Zhang ◽  
Shuangjiao Gan ◽  
Yunqi Liu ◽  
Huayang Li ◽  
...  

Long noncoding RNAs (lncRNAs) and microRNAs (miRNAs) are involved in the mechanism underlying cerebral dysfunction after deep hypothermic circulatory arrest (DHCA), although the exact details have not been elucidated. To explore the expression profiles of lncRNAs and miRNAs in DHCA cerebral injury, we determined the lncRNA, miRNA and mRNA expression profiles in the cerebral cortex of DHCA and sham rats. First, a rat model of DHCA was established, and high-throughput sequencing was performed to analyze the differentially expressed RNAs (DERNAs). Then, the principal functions of the significantly deregulated genes were identified using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Expression networks (lncRNAs-miRNAs-mRNAs and transcription factors (TFs)-miRNAs-mRNAs) were also established. Finally, the expression of DERNAs was confirmed by quantitative real-time PCR (RT-qPCR). We identified 89 lncRNAs, 45 miRNAs and 59 mRNAs between the DHCA and sham groups and constructed a comprehensive competitive endogenous RNAs (ceRNAs) network. A TF-miRNA-mRNA regulatory network was also established. Finally, we predicted that Lcorl-miR-200a-3p-Ttr, BRD4-Ccl2 and Ep300-miR-200b-3p-Tmem72 may participate in the pathogenesis of DHCA cerebral injury.

Perfusion ◽  
2009 ◽  
Vol 24 (6) ◽  
pp. 429-436 ◽  
Author(s):  
Kristine Kellermann ◽  
M. Lucia Gordan ◽  
Georg Nollert ◽  
Manfred Blobner ◽  
Eberhard F. Kochs ◽  
...  

Objectives: Inflammatory response is discussed as a contributor to neurologic deficits following cardiac surgery using deep hypothermic circulatory arrest (DHCA). Nuclear Factor Kappa B (NFκB) presents a central transcription factor whose expression pattern and subsequent role very much depend on the type and manner of cerebral injury. This study was designed to assess the time course of cerebral NFκB expression in relation to neurologic performance over 28 days following 45min of DHCA in rats. Methods: With Institutional Review Board approval, 30 rats were subjected to cardiopulmonary bypass (CPB) with 45min of DHCA (rectal temperature 15-18°C) and randomly assigned to 1, 3, 7, 14 and 28 days of postoperative survival. Untreated animals served as control (n=6). Cerebral NFκB expression was analyzed immunohistochemically, cyclooxygenase-2 (COX-2) and inhibitor of kappa B-alpha (IκBα) using Western Blot and the number of eosinophilic neurons with hematoxylin and eosin (HE) staining. Neurologic outcome was assessed pre- and postoperatively. Results: Neuronal expression of NFκB in the hippocampus peaked at day one, remaining elevated in the motor cortex until day 28. Rats showed neurologic deficits on postoperative day one. Cerebral COX-2 was increased during the first postoperative week and IκBα peaked on day 14. Histologic damage in the motor cortex and hippocampus persisted until day 28. No systemic inflammation was detectable postoperatively. Conclusions: Postoperative day one presents with the highest NFκB-expression in the ischemia-sensitive hippocampus, accompanied by neurologic dysfunction and histologic damage following 45min of DHCA in rats.


1995 ◽  
Vol 82 (1) ◽  
pp. 74-82 ◽  
Author(s):  
Dean C. Kurth ◽  
James M. Steven ◽  
Susan C. Nicolson

Background Deep hypothermic circulatory arrest is a widely used technique in pediatric cardiac surgery that carries a risk of neurologic injury. Previous work in neonates identified distinct changes in cerebral oxygenation during surgery. This study sought to determine whether the intraoperative changes in cerebral oxygenation vary between neonates, infants, and children and whether the oxygenation changes are associated with postoperative cerebral dysfunction. Methods The study included eight neonates, ten infants, and eight children without preexisting neurologic disease. Cerebrovascular hemoglobin oxygen saturation (SCO2), an index of brain oxygenation, was monitored intraoperatively by near-infrared spectroscopy. Body temperature was reduced to 15 degrees C during cardiopulmonary bypass (CPB) before commencing circulatory arrest. Postoperative neurologic status was judged as normal or abnormal (seizures, stroke, coma). Results Relative to preoperative levels, the age groups experienced similar changes in SCO2 during surgery: SCO2 increased 30 +/- 4% during deep hypothermic CPB, it decreased 62 +/- 5% by the end of arrest, and it increased 20 +/- 5% during CPB recirculation (all P < 0.001); after rewarming and removal of CPB, SCO2 returned to preoperative levels. During arrest, the half-life of SCO2 was 9 +/- 1 min in neonates, 6 +/- 1 min in infants, and 4 +/- 1 min in children (P < 0.001). Postoperative neurologic status was abnormal in three (12%) patients. The SCO2 increase during deep hypothermic CPB was less in these patients than in the remaining study population (3 +/- 2% versus 33 +/- 4%, P < 0.001). There were no other significant SCO2 differences between outcome groups. Conclusions Brain oxygenation changed at distinct points during surgery in all ages, reflecting fundamental cerebral responses to hypothermic CPB, ischemia, and reperfusion. However, the changes in SCO2 half-life with age reflect developmental differences in the rate of cerebral oxygen utilization during arrest, consistent with experimental work in animals. Certain intraoperative cerebral oxygenation patterns may be associated with postoperative cerebral dysfunction and require further study.


1999 ◽  
Vol 117 (6) ◽  
pp. 1204-1211 ◽  
Author(s):  
Toshiharu Shin'oka ◽  
Mitsugi Nagashima ◽  
Georg Nollert ◽  
Dominique Shum-Tim ◽  
Peter C. Laussen ◽  
...  

2015 ◽  
Vol 18 (4) ◽  
pp. 124
Author(s):  
Mehmet Kaplan ◽  
Bahar Temur ◽  
Tolga Can ◽  
Gunseli Abay ◽  
Adlan Olsun ◽  
...  

<p><strong>Background</strong><strong>: </strong>This study aimed to report the outcomes of patients who underwent proximal thoracic aortic aneurysm surgery with open distal anastomosis technique but without cerebral perfusion, instead under deep hypothermic circulatory arrest.</p><p><strong>Methods: </strong>Thirty patients (21 male, 9 female) who underwent ascending aortic aneurysm repair with open distal anastomosis technique were included. The average age was 60.2±11.7 years. Operations were performed under deep hypothermic circulatory arrest and the cannulation for cardiopulmonary bypass was first done over the aneurysmatic segment and then moved over the graft. Intraoperative and early postoperative mortality and morbidity outcomes were reported.</p><p><strong>Results</strong><strong>: </strong>Average duration of cardiopulmonary bypass and cross-clamps were 210.8±43 and 154.9±35.4 minutes, respectively. Average duration of total circulatory arrest was 25.2±2.4 minutes. There was one hospital death (3.3%) due to chronic obstructive pulmonary disease at postoperative day 22. No neurological dysfunction was observed during the postoperative period.<strong></strong></p><p><strong>Conclusion: </strong>These results demonstrate that open distal anastomosis under less than 30 minutes of deep hypothermic circulatory arrest without antegrade or retrograde cerebral perfusion and cannulation of the aneurysmatic segment is a safe and reliable procedure in patients undergoing proximal thoracic aortic aneurysm surgery.</p><p> </p>


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