Cardiopulmonary toxicity of delta-9-tetrahydrocannabinol in the anesthetized dog.

Eighteen anesthetized dogs were treated with 0.5 mg/kg Δ⁹-tetrahydrocannabinol (THC) or control vehicle by iv injection, and cardio-pulmonary responses were determined in intact and vagotomized animals. Blood specimens were examined periodically for pO₂, pCO₂, pH, and lactate and pyruvate concentrations. In addition, cardiac output, heart rate, and lung compliance (C_L) and resistance (R_L) were measured. Δ⁹-Tetrahydrocannabinol markedly increased R_L in intact dogs but not in vagotomized dogs, while C_L remained essentially unchanged in both intact and vagotomized animals. The administration of THC had no effect on arterial blood gases in intact or vagotomized dogs as compared to controls. However, intact animals, unlike those vagotomized, exhibited a significant decrease in blood pH. Bradycardia developed in intact animals (28% decrease in heart rate), which could not be completely prevented by vagotomy (17% decrease in heart rate). Cardiac output also decreased in intact and, to a lesser extent, in vagotomized animals. Diminished cardiac output was associated with metabolic acidosis characterized by an increase in blood lactate and in the lactate-pyruvate ratio. The administration of THC in dogs resulted in an increase in R_L, which appears to be vagally mediated and is not accompanied by a decrease in C_L or blood gas changes.