Jr. Kambam et al., THE EFFECT OF HEPATECTOMY AND PLASMA CHOLINESTERASE INHIBITION ON COCAINE METABOLISM AND CARDIOVASCULAR-RESPONSES IN PIGS, The Journal of laboratory and clinical medicine, 124(5), 1994, pp. 715-722
Citations number
20
Categorie Soggetti
Medical Laboratory Technology","Medicine, General & Internal
To determine the effects of total hepatectomy and inhibition of plasma
cholinesterase activity on cocaine metabolism, we measured plasma con
centrations of cocaine and its three major metabolites, benzoylecgonin
e, ecgonine methyl ester, and norcocaine, by high-performance liquid c
hromatography in three groups of male pigs. Rigs were anesthetized wit
h sodium thiopental and lungs were ventilated with nitrous oxide in ox
ygen. A right carotid arterial cannula and an internal jugular venous
catheter were then inserted for the administration of cocaine and for
blood sampling. A Swan-Ganz catheter was inserted through the right in
ternal jugular vein. Group 1 pigs underwent sham operation; group 2 an
d 3 pigs underwent hepatectomy and portocaval shunt. In addition, grou
p 3 pigs were treated with tetraisopropyl pyrophosphoramide, a specifi
c plasma cholinesterase inhibitor. After this preparation, pigs were g
iven 4 mg/kg cocaine intravenously over 2 minutes. After cocaine injec
tion, 4 mi blood was collected into heparinized test tubes containing
2.5% sodium fluoride for determination of cocaine and its metabolites
at 2, 5, 10, 15, 30, 45, 60, 90, 120, 180, 240, and 300 minutes. We al
so measured hemodynamic responses after cocaine administration, includ
ing heart rate and rhythm, cardiac output, and arterial blood pressure
. Data were analyzed by analysis of variance. Blood levels of cocaine
and its metabolites were significantly different among the three group
s (p < 0.05 by analysis of variance). Our results show that total hepa
tectomy was associated with a marked slowing of cocaine metabolism, ab
sence of norcocaine, and increased benzoylecgonine levels when compare
d with the baseline values in the control pigs. Hepatectomy and plasma
cholinesterase inhibition together were associated with a marked decr
ease in ecgonine methyl ester levels in group 3 compared with group 4
(control pigs) and group 2 (anhepatic pigs). Our results also indicate
that plasma cholinesterase inhibition has a protective effect against
cardiovascular disturbances Induced by cocaine administration in anhe
patic animals.