Direct and indirect activation of the adenosine triphosphate–sensitive potassium channel to induce spinal cord ischemic metabolic tolerance
| Autor: | Xianzhong Meng, Joseph C. Cleveland, Christian V. Ghincea, Gavriel F. Roda, Linling Cheng, Michael J. Weyant, David A. Fullerton, T. Brett Reece, Yuki Ikeno, Muhammad Aftab |
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| Rok vydání: | 2023 |
| Předmět: |
Pulmonary and Respiratory Medicine
business.industry Ischemia Pharmacology medicine.disease Adenosine Potassium channel Nitric oxide chemistry.chemical_compound chemistry medicine Diazoxide Surgery Potassium channel opener Cardiology and Cardiovascular Medicine Nicorandil business Spinal cord injury medicine.drug |
| Zdroj: | The Journal of Thoracic and Cardiovascular Surgery. 165:e90-e99 |
| ISSN: | 0022-5223 |
| Popis: | OBJECTIVES The mitochondrial adenosine triphosphate-sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide-dependent indirect activation of the adenosine triphosphate-sensitive potassium channel contribute to the induction of ischemic metabolic tolerance. METHODS Spinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate-sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate-sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia. RESULTS Motor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P |
| Databáze: | OpenAIRE |
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