Dihydrocapsaicin-induced hypothermia after asphyxiai cardiac arrest in rats

Cardiac arrest (CA) is one of the leading causes of mortality and morbidity in the world. Fast, reversible and controllable pharmaceutical-induced hypothermia (PIH) is strongly desired to treat ischemia-reperfusion brain injury. Dihydrocapsaicin (DHC), an agonist of transient receptor potential vanilloid type 1 cation channel (TRPV1), is an emerging candidate for PIH. Its capability to lower body temperature has been validated in both healthy and stroke animal models. However, DHC has shown cardiovascular effects and its safety and feasibility in a CA model has not been tested. Additionally, activated TRPV1 has multiple functions in addition to regulating body temperature and its effect on neurological recovery needs to be evaluated. In this study, we compared two methods of DHC administration, bolus injection and infusion via the femoral vein. We found that cardiovascular effects were only seen with a large dose DHC bolus injection. Then, we applied DHC-induced hypothermia in an asphyxial-CA rat model. We showed that DHC-treated rats were viable. Four-hour infusion of DHC at a rate of 0.75 mg/kg/h after CA maintained a body temperature of about 34 °C for at least 8 hours. DHC-treated rats had higher electrical activity during the first 4 hours after CA and had better neurological recovery during the 3 days after CA compared with normothermia rats. Additional pathway investigation of DHC administration following CA will further uncover the benefits of DHC-induced hypothermia.