6N‐Cyclohexyladenosine Suppresses Shivering in Anesthetized Swine

• DOI: 10.1096/fasebj.31.1_supplement.lb607
• Publication Date: 2023-11-26T17:01:18Z
• Authors: Kelly L Drew; Ø Tøien; Matthew M Kumar
• Keywords: Shivering

Shivering compromises post‐operative recovery and patient comfort. is also an impediment to targeted temperature management (TTM), now standard of care for cardiac arrest. Without effective drug suppress shivering (referred here as a thermolytic) high cost difficulty restricting access TTM outside large hospitals conditions such stroke. A more efficacious thermolytic needed control improve comfort during TTM. Our prior work in rats, based on strong scientific premise from the study hibernating animals, suggests that stimulating CNS 1 adenosine receptors (A AR) by combining AR agonist 6 N cyclohexyladenosine (CHA) with peripherally acting receptor antagonist 8‐(p‐sulphophenyl)theophylline (8‐SPT) will provide means shivering. This approach works rodents however, efficacy has not been demonstrated larger mammal that, like humans, depends primarily thermogenesis maintain body temperature. To assess CHA 50–55 kg swine, species lacks brown adipose tissue, three pigs were anesthetized Telazol/Xylazine, propofol, or isoflurane cooled target 32 34°C water blanket set 4°C. Probes measured core at tympanum, lower esophagus, rectum bladder. Electrocardiography, pulse oximetery arterial blood pressure monitored. was respirometry qualitative visual scale. When noted, administered (bolus, 4.2mg; infusion,113μg/kg/h). 8‐SPT 186mg), atropine 0.5mg) epinephrine 100μg) then given IV reverse bradycardia hypotension. At completion, animals euthanized tissues collected histopathology. Results show inhibits restores heart rate without reversing effect CHA. No histopathology noted. In conclusion, swine. Support Funding Information supported Be Cool Pharmaceutics LLC Mayo Clinic