Meglumine cyclic adenylate improves cardiovascular hemodynamics and motor-function in a rat model of acute T4 thoracic spinal cord injury.

Autor: Song Y; Department of Orthopedic Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China., Guo L; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Jiang X; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Dong M; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Xiang D; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Wen M; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., He S; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Yuan Y; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Lin F; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Zhao G; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Liu L; Department of Orthopedic Surgery, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China., Liao J; Orthopedic-Traumatology Department, The 2nd Affiliated Hospital of Kunming Medical University, Kunming, 650101, Yunnan, China. liaojingwu_hx@sohu.com.
Jazyk: angličtina
Zdroj: Spinal cord [Spinal Cord] 2023 Aug; Vol. 61 (8), pp. 422-429. Date of Electronic Publication: 2023 Jul 04.
DOI: 10.1038/s41393-023-00909-y
Abstrakt: Study Design: Animal experimental study.
Objectives: Spinal cord injury (SCI) at or above the T6 level causes cardiovascular dysfunction. Maintaining cAMP levels with cAMP analogs can facilitate neurological recovery. In the present study, the effects of meglumine cyclic adenylate (MCA), a cAMP analog and approved cardiovascular drug, on cardiovascular and neurological recovery in acute T4-SCI in rats were investigated.
Setting: Hospital in Kunming, China.
Methods: Eighty rats were randomly allocated to five groups, and groups A-D received SCI: (A) a group administered MCA at 2 mg/kg/d iv qd, (B) a group administered dopamine at 2.5 to 5 μg/kg/min iv to maintain mean arterial pressure above 85 mm Hg, (C) a group administered atropine at 1 mg/kg iv bid, (D) a group receiving an equal volume of saline iv qd for 3 weeks after SCI and (E) a group undergoing laminectomy only. The cardiovascular and behavioral parameters of the rats were examined, and spinal cord tissues were processed for hematoxylin and eosin staining, Nissl staining, electron microscopy, and analysis of cAMP levels.
Results: Compared with dopamine or atropine, MCA significantly reversed the decrease in cAMP levels in both myocardial cells and the injured spinal cord; improved hypotension, bradycardia and behavioral parameters at 6 weeks; and improved spinal cord blood flow and histological structure at 7 days post-SCI. The regression analysis suggested spinal cord motor-function improved as decreased heart rate and mean arterial pressure were stopped post-SCI.
Conclusions: MCA may be an effective treatment for acute SCI by sustaining cAMP-dependent reparative processes and improving post-SCI cardiovascular dysfunction.
Sponsorship: N/A.
(© 2023. The Author(s), under exclusive licence to International Spinal Cord Society.)
Databáze: MEDLINE
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