Minimum Alveolar Concentration of Isoflurane in Rats Chronically Treated with the Synthetic Cannabinoid WIN 55,212-2

Simple Summary The minimum alveolar concentration of isoflurane (inhaled anesthetic required to prevent movement in 50% of subjects exposed to a supramaximal noxious stimulus) was determined in 24 male rats chronically treated with the synthetic cannabinoid WIN 55,212-2 to evaluate the interaction of isoflurane with chronically administered cannabinoid agonist. The minimum alveolar concentration was determined in one group without treatment, in rats treated for 21 days with WIN 55,212-2, and another group 8 days after stopping treatment for 21 days with cannabinoid. We believe it is necessary to study the effects of chronic consumption of these substances on the requirements of inhalation anesthetics in patients that will be submitted to general anesthesia. The administration for 21 days of WIN 55,212-2 increases the minimum alveolar concentration of isoflurane in rats; this effect does not disappear after 8 days of discontinuing treatment with the synthetic cannabinoid. The minimum alveolar concentration MAC of isoflurane was measured in rats chronically treated with WIN 55,212-2. Methods: The MAC of isoflurane was determined in 24 male rats from expiratory samples at time of tail clamping under the following conditions: without treatment MAC((ISO)), in rats treated for 21 days with WIN 55,212-2 MAC((ISO + WIN55)), and in rats 8 days after stopping treatment with WIN 55,212-2 (MAC(ISO + WIN55 + 8D)). Results: The MAC((ISO)) was 1.32 +/- 0.06. In the MAC((ISO + WIN55)) group, the MAC increased to 1.69 +/- 0.09 (28%, p-value <= (0.0001). Eight days after stopping treatment with WIN55, the MAC did not decrease significantly, 1.67 +/- 0.07 (26%, p-value <= 0.0001). Conclusions: The administration of WIN 55,212-2 for 21 days increases the MAC of isoflurane in rats. This effect does not disappear 8 days after discontinuation of treatment with the synthetic cannabinoid.

Automated summary

The minimum alveolar concentration of isoflurane was determined in male rats treated with WIN 55,212-2, showing an increase in minimum alveolar concentration after chronic use. This effect persisted even after discontinuation of the synthetic cannabinoid for 8 days.