Effects of Aerosolized Carfentanil on Cardiac Function in Ferrets

Abstract

Carfentanil (CRF) is a potent synthetic opioid primarily used in anaesthetizing large animals. Exposure to CRF can cause both respiratory and central nervous system depression. Respiratory depression can lead to hypoxia, which may lead to cardiac damage and ultimately death. Myocardial damage has been observed in ferrets exposed to aerosolized CRF. Troponin is a protein complex that plays an integral part in muscle contractions within the myocardium and is used as an indicator of myocardial damage. An increase in blood levels of troponin in exposed ferrets would suggest underlying cardiac damage. Select animals were treated with naloxone (NX), an opioid antagonist, to investigate whether reversing opioid effects altered cardiac function or troponin levels. Male telemetrized ferrets were exposed to aerosolized CRF in a whole‐body plethysmography chamber. Cardiac parameters and respiratory dynamics were collected before, during, and after CRF exposure. Ferrets received no treatment, an oral or intramuscular (i.m.) dose of NX (0.375, 0.75, 1.5, or 3 mg/mL), or water 30 minutes post‐exposure. Euthanasia occurred 24 hours post‐exposure, and blood was collected via descending aorta or heart stick. Serum was separated from blood and analyzed using a high sensitivity rat cardiac troponin‐I enzyme‐linked immunosorbent assay (ELISA). Average troponin levels for all animals ranged from 0.00 – 6.30 ng/mL. Troponin levels were not statistically different across treatment groups, though we observed an increase in mean arterial pressure (MAP) and increased incidents of premature junction complexes for animals exposed to CRF, indicating potential cardiac distress. The increase in MAP could be a compensatory mechanism to overcome hypoxia due to decreased respiration induced by CRF. Both control and exposed animals showed an increase in MAP following treatment; however, sham‐exposed animals had no rise in MAP post‐treatment. This rise in MAP could be due to a combination of NX treatment and a response to being handled for the injection. Overall, our results suggest that CRF does not directly cause myocardial damage, nor do surgically implanted cardiac telemetry devices cause an explicit, permanent increase in troponin levels. Further investigation is needed to determine if cardiac abnormalities observed in ferrets are caused via hypoxia or other unknown mechanisms. Support or Funding Information Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the US Army. This research complied with the Animal Welfare Act and implementing Animal Welfare Regulations and adhered to the principles noted in The Guide for the Care and Use of Laboratory Animals. This research was supported by DTRA RD‐CB. E.P., W.Y.T., M.R. S.P., A.D., and V.D.C. were supported in part by an appointment to the Postgraduate Research Participation Program at the US Army Medical Research Institute of Chemical Defense administered by the Oak Ridge Institute for Science and Education through an interagenc...