A long-term survival rat model of spinal cord ischemia injury: Thoracic aortic occlusion combined with aortic bypass circulation.

OBJECTIVE: This study aims to investigate the methods for rat spinal cord ischemia injury models with a high long-term survival rate. METHODS: The rats were divided into three groups: the treatment group, the control group, and the sham operation group. The treatment group had a blocked thoracic aorta (landing zone 3 by Ishimaru - T11) + aortic bypass circulation for 20 min. In the control group, the thoracic aorta at the landing zone 3 was blocked for 20 min. In the sham operation group, only thoracotomy without thoracic aortic occlusion was performed. The mean arterial blood pressure (MABP) of the thoracic aorta and caudal artery before and after thoracic aortic occlusion was monitored intraoperatively. Spinal cord function was monitored by a transcranial motor evoked potential (Tc-MEP) during the operation. Spinal cord function was evaluated by the BBB scale (Basso, Beattie, & Bresnahan locomotor rating scale) scores at multiple postoperative time points. The spinal cord sections of the rats were observed for 7 days after surgery, and the survival curves were analyzed for 28 days after surgery. RESULTS: After aortic occlusion, the MABP of thoracic aorta decreased to 6% of that before occlusion, and the MABP of caudal artery decreased to 63% of that before occlusion in the treatment group. In the control group, the MABP of both thoracic aorta and caudal artery decreased to 19% of that before occlusion. The Tc-MEP waveform of the treatment group disappeared after 6 min, and that of the control group disappeared after 8 min until the end of surgery. There was no change in the Tc-MEP waveform in the sham operation group. The BBB score of the treatment group decreased more obviously than the control group, and there was a significant difference. There was no decrease in the sham group. Spinal cord sections showed a large number of degeneration and necrosis of neurons, infiltration of inflammatory cells, and proliferation of surrounding glial cells in the treatment group. In the control group, multiple neurons were necrotic. The histology of the sham operation group was normal. The 28-day survival rate of the treatment group was 73.3%, which was higher than the control group (40.0%), and there was a significant difference (p < 0.05). CONCLUSION: Thoracic aortic occlusion combined with aortic bypass is an effective modeling method for rats with accurate modeling effects and high long-term survival rates.

Comprehensive microRNA profiling reveals potential augmentation of the IL1 pathway in rheumatic heart valve disease.

BACKGROUND: Valvular heart disease is a leading cause of cardiovascular mortality, especially in China. More than a half of valvular heart diseases are caused by acute rheumatic fever. microRNA is involved in many physiological and pathological processes. However, the miRNA profile of the rheumatic valvular heart disease is unknown. This research is to discuss microRNAs and their target gene pathways involved in rheumatic heart valve disease. METHODS: Serum miRNA from one healthy individual and four rheumatic heart disease patients were sequenced. Specific differentially expressed miRNAs were quantified by Q-PCR in 40 patients, with 20 low-to-moderate rheumatic mitral valve stenosis patients and 20 severe mitral valve stenosis patients. The target relationship between certain miRNA and predicted target genes were analysis by Luciferase reporter assay. The IL-1ß and IL1R1 expression levels were analyzed by immunohistochemistry and western blot in the mitral valve from surgery of mitral valve replacement. RESULTS: The results showed that 13 and 91 miRNAs were commonly upregulated or downregulated in all four patients. Nine miRNAs, 1 upregulated and 8 downregulated, that had a similar fold change in all 4 patients were selected for quantitative PCR verification. The results showed similar results from miRNA sequencing. Within these 9 tested miRNAs, hsa-miR-205-3p and hsa-miR-3909 showed a low degree of dispersion between the members of each group. Hsa miR-205-3p and hsa-miR-3909 were predicted to target the 3'UTR of IL-1ß and IL1R1 respectively. This was verified by luciferase reporter assays. Immunohistochemistry and Western blot results showed that the mitral valve from rheumatic valve heart disease showed higher levels of IL- 1ß and IL1R1 expression compared with congenital heart valve disease. This suggested a difference between rheumatic heart valve disease and other types of heart valve diseases, with more inflammatory responses in the former. CONCLUSION: In the present study, by next generation sequencing of miRNAs, it was revealed that interleukin 1ß and interleukin 1 receptor 1 was involved in rheumatic heart diseases. And this is useful for diagnosis and understanding of mechanism of rheumatic heart disease.

Aorta-Iliac Bypass in Thoracoabdominal Aortic Aneurysm Repair in Young Chinese Patients.

BACKGROUND: Many surgical methods of thoracoabdominal aortic aneurysm repair (TAAAR) have been introduced over the past several decades, with varying degrees of success. We developed an aorta-iliac bypass technique to treat thoracoabdominal aortic aneurysm (TAAA) in young Chinese patients. The aim of this study is to evaluate the results of this technique intraoperatively and postoperatively. METHODS: From June 2014 to March 2015, 28 patients underwent TAAAR using aorta-iliac bypass technique. A four-branched tetrafurcate graft was used. Two branches of the graft are sutured to bilateral common iliac arteries in an end-to-side fashion. The trunk of the graft was sutured to the proximal descending aorta in an end-to-end fashion. Then aorta-iliac bypass was established, and the lower extremities, viscera organ and spinal cord (SC) obtained perfusion from proximal descending aorta via the bypass graft. The thoracic and abdominal aorta were clamped in a staged fashion. The patent segmental arteries (SAs), and visceral arteries (coeliac trunk, superior mesenteric arteries, and renal arteries) were reattached sequentially. Evoked potential (EP) monitoring was adopted to assess the SC ischaemia throughout the procedure. The postoperative outcomes and follow-up results of this technique were evaluated. RESULTS: There was no in-hospital mortality. Complications included acute kidney dysfunction and pulmonary haemorrhage in one case (3.6%) each. The SAs were reattached in all cases. The EP wave disappeared after proximal descending aorta was clamped, and gradually recovered after the patent SAs reattached. The median follow-up after operation was eight months (range, 1-10 months). There was no delayed neurologic deficit or late death. CONCLUSIONS: Thoracoabdominal aortic aneurysm repair using aorta-iliac bypass may be a simple and safe choice for young Chinese patients with thoracoabdominal aortic aneurysms.

[Effect of aorta-iliac bypass total thoracoabdominal aorta aneurysm repair to spinal cord function].

OBJECTIVE: To evaluate the effect of aorta-iliac bypass total thoracoabdominal aorta aneurysm repair to spinal cord function. METHODS: This was a prospective study. From June 2014 to April 2015, 31 patients underwent total thoracoabdominal aorta aneurysm repair were treated with aorta-iliac bypass technique. There were 23 male and 8 female patients with a mean age of (36±12) years. A 4-branched tetrafurcate graft was used. The aorta-iliac bypass was established, then distal descending aorta was perfused in a retrograde fashion via bypass graft. Thoracic and abdominal aorta were replaced in a staged fashion. Evoked potentials (EP) monitoring was adopted to assess the spinal cord ischemia throughout the procedure. The intraoperative evoked potentials results, clinical outcomes and follow-up results of this technique were evaluated. RESULTS: The EP wave disappeared after proximal descending aorta clamped and gradually recovered after the patent segmental arteries reattached. Motor evoked potentials disappeared for (56±18) minutes, somatosensory evoked potentials disappeared for (50±19) minutes. The EP wave was restored to normal at the end of operation in all cases. The somatosensory evoked potentials remained unchanged in 2 cases (false negative). One case died after operation. There were acute kidney dysfunction in 3 cases, and pulmonary haemorrhage in 1 case. No spinal cord injure occurred. The median follow-up after operation was 8 months (ranging from 1 to 11 months). There was no delayed neurologic deficit or relative death. CONCLUSIONS: There is a transient function loss of spinal cord during the aorta-iliac bypass total thoracoabdominal aorta aneurysm repair. But the process is reversible. The technique of the aorta-iliac bypass is practicable.

Low concentration of rutin treatment might alleviate the cardiotoxicity effect of pirarubicin on cardiomyocytes via activation of PI3K/AKT/mTOR signaling pathway.

Cancer is the leading cause of deaths around the world, especially in low- and middle- income countries. Pirarubicin (THP) is an effective drug for treatment of cancer, however, there still exists cardiotoxic effects of THP. Rutin is a kind of antioxidative compound extracted from plants, and might be a protective compound for cardiomyocytes. Phosphatidylinositol 3-hydroxy kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is critical for cellular survival, proliferation and metabolism, and thus we speculated rutin might perform a protective role in cardiomyocytes via PI3K/AKT/mTOR signaling pathway. And in this experiment, we first established a cardiotoxicity model of THP in mice model and cell models, and then found that rutin treatment could increase the proliferation of cells at low concentration. Then we explored the possible mechanism of the protective effect of rutin using Western blotting, quantitative polymerase chain reaction (qPCR) and ELISA methods, and found that the activation of PI3K/AKT/mTOR/nuclear factor-κB (NF-κB) signaling pathway was increased, and expression of downstream molecules involved in antioxidative stress were also increased. We further noticed that concentration of angiogenesis promoting factors were also increased in medium of cultured cells. Thus, we speculated that rutin could increase the activation of PI3K/AKT/mTOR signaling pathway, further decrease the oxidative stress level via increasing the expression of antioxidative stress enzymes with the increasing concentration of angiogenesis promoting factors, resulting in the protective role in cardiomyocytes and cardiac function.