Cocaine residue in plasma, cardiac and tracheal tissues of chronic cocaine-treated guinea-pigs
Malinee Wongnawa, Sawpheeyah Nima, Peerarat Thaina and Methi Sunbhanich
pp. 43 - 49
Abstract
Supersensitivity of adrenoceptors to catecholamines is one of the mechanisms of cocaine-related cardiac complication. The precise mechanism of cocaine enhancing supersensitivity of adrenoceptors is unconcluded. The aim of this study was to determine the levels of cocaine in plasma, cardiac and tracheal tissues in order to correlate with the supersensitivity of adrenoceptors to catecholamines. In this study, two groups of ten guinea-pigs each were injected with 2.5 mg/kg cocaine or normal saline solution intraperitoneally twice daily for 14 days. After 24 hours of cocaine cessation, the cocaine levels in plasma, cardiac and tracheal tissues were determined using high performance liquid chromatography. The results showed that the cocaine levels in plasma and tracheal smooth muscle were 5.08±0.63 ng/ml and 2.8±0.41 ng/mg, respectively, while those in atria and ventricle were lower than 17.5 ng/g and 3.8 ng/g, respectively. These levels were less than the level that had been reported to block norepinephrine uptake (more than 30.34 ng/ml). Moreover, it had been demonstrated that cocaine treatment in the same condition as the present study produced supersensitivity to norepinephrine and epinephrine in isolated guinea-pig atria as well as in trachea which is almost entirely not innervated by the adrenergic nerves. In addition, supersensitivity to oxymetazoline, isoproterenol and salbutamol which are not the substrates of neuronal reuptake were also demonstrated. All these data support the postsynaptic mechanism of cocaine enhancing supersensitivity which might be correlated with cardiac complication in chronic cocaine use.
