| Autor: |
Tsoporis, James N, Ektesabi, Amin, Izhar, Shehla, dos Santos, Claudia, Parker, Thomas G, Leong-Poi, Howard, Rizos, Ioannis K, Apapalois, Apostolos E, Toumpoulis, Stavros K, Toumpoulis, Ioannis K |
| Zdroj: |
Circulation (Ovid); November 2022, Vol. 146 Issue: Supplement 1 pA13235-A13235, 1p |
| Abstrakt: |
Introduction:Spinal cord injury and subsequent paraplegia represents a devastating complication of thoracoabdominal aortic surgery. Pro-inflammatory cytokine expression and spinal cord neuronal apoptosis have been implicated in inflammation and neurodegeneration respectively after ischemia.Hypothesis:We investigated the neuroprotective effects of the steroid antioxidant Lazaroid U-74389G versus conventional ischemic preconditioning (IPC) in a pig model of spinal cord ischemia-reperfusion injury by examining the expression of pro-inflammatory and pro-apoptotic S100 members and the receptor for advanced glycation end products (RAGE).Methods:Spinal cord ischemia was induced by thoracoabdominal aortic occlusion (TAO). A total of 27 pigs were randomized in four groups. Group I (n=5) sham operation, group II (n=7) TAO for 45min and received placebo, group III (n=8) received 3 doses of Lazaroid (3 mg/kg) 60min and 30min before and at 30min during TAO (duration 45min), and group IV (n=6) TAO for 20min followed by additional TAO for 45min and 80 minutes later. Neurologic evaluation was performed according to Tarlov score (0-4, 4=normal). The lumbar spinal cords were harvested at 7th postoperative day for the expression of inflammatory and apoptotic markers by real-time RT-PCR.Results:Group III and IV had better neurologic outcome postoperatively compared to group II where all animals developed paraplegia (Tarlov scores: 3.5 versus 3.6 versus 0.33, respectively, P<0.001). Group II showed marked pro-inflammatory responses as quantified by 2-4-fold increases in the mRNA of pro-inflammatory S100A6, S100A8 and high-mobility group box 1, and RAGE, compared to group I. Additionally, group II, exhibited apoptosis as quantified by a 40-60% decrease in the mRNA of anti-apoptotic BCL2 and BIRC2, and 2-3-fold increases in pro-apoptotic BAX mRNA and caspase 3 activity. Compared to group II, inflammatory and apoptotic responses were highly attenuated albeit to a similar degree in groups III and IV.Conclusions:In a large animal model very close to the clinical setting, we demonstrated that in addition to IPC, Lazaroid represents an alternative yet effective pharmacologic intervention in reducing spinal cord ischemia-reperfusion injury following TAO. |
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