Acute Coronary Syndrome ; chemically induced ; Anesthetics, Dissociative ; adverse effects ; Humans ; Ketamine ; adverse effects

The abuse of ketamine has gained popularity in recent years. It is important to develop rapid and accurate methods to determine ketamine and its metabolites in biological samples. The metabolites of ketamine are norketamine and dehydronorketamine in vivo. At present, there are blood, urine, hair and so on as specimens for detection, while the methods include GC, GC/MS, HPLC, LC/MS, HPCE etc. In this paper, these methods used for ketamine and its metabolites were reviewed in order to provide some preference for the study in relative fields.
Anesthetics, Dissociative/chemistry* ; Chromatography, High Pressure Liquid/methods* ; Forensic Medicine ; Gas Chromatography-Mass Spectrometry/methods* ; Hair/chemistry* ; Humans ; Ketamine/metabolism* ; Sensitivity and Specificity ; Substance Abuse Detection/methods*

OBJECTIVETo study the psychedelic effects in healthy volunteers when given subanesthetic dose of ketamine.

METHODSThirteen male healthy volunteers aged 24-39 years were enrolled. All subjects received subanesthetic doses of ketamine using target control infusion. A stepwise series of target plasma concentrations (0, 100, 200, and 300 ng/ml) were maintained for 20 minutes each. Visual analogue scale (VAS) of mechanical pain by von Frey hair was evaluated, and then the volunteers completed a VAS rating of 13 symptom scales. Pictures were shown to them at the same time. Heart rate, mean blood pressure, and SpO2 were monitored throughout the infusion.

RESULTSDuring the process of analgesia, ketamine produced dose-related analgesic effects. With the increase of ketamine dose, some psychedelic effects became more obvious and the memory impairment became worse stepwisely.

CONCLUSIONTarget control infusion of subanesthetic doses of ketamine produce obvious psychedelic effects in healthy volunteers.

Adult ; Anesthetics, Dissociative ; administration & dosage ; adverse effects ; pharmacology ; Dose-Response Relationship, Drug ; Hallucinations ; chemically induced ; Humans ; Ketamine ; administration & dosage ; adverse effects ; pharmacology ; Male

OBJECTIVETo summarize the anesthetic management in fetal lamb cardiac bypass.

METHODSFive ewes at 120-140 days of gestation were anesthetized intramuscularly with katamine hydrochloride, intubated and ventilated with a respirator. Anesthesia was maintained with fentanyl and vecuronium. Lactated Ringer's solution and magnesium sulfate were infused to maintain the mean blood pressure (MAP) over 70 mmHg and uterine relaxation. The fetal lambs received anesthesia with fentanyl and vecuronium intramuscularly via the uterine wall. Fetal cardiac bypass was established with pulmonary artery and right atrium cannulation, lasting for 30 min. The hemodynamic and blood gas data of the ewes and fetal lambs were recorded before bypass, at 30 min during bypass, and at 1 and 2 h after cessation of bypass. The pulse index of the umbilical artery (PIua) and the ewe's uterine artery (PIeu) were monitored simultaneously.

RESULTSThe MAP and heart rate (HR) of the fetus remained normal during the anesthesia. PIua increased significantly after cessation of bypass (P<0.05). Although the fetal oxygen tension in the axillary artery remained normal, the fetal lambs showed hypercarbia and acidosis after cessation of bypass (P<0.05). The maternal MAP and HR remained normal. The PIeu decreased significantly during bypass (P<0.05) and recovered the normal level after cessation of bypass. The arterial blood gas of the ewes was normal during the experiment.

CONCLUSIONMaintaining high hemodynamics in the ewes, application of uterine relaxation and intensive care during anesthesia are crucial in anesthetic management of cardiac bypass in fetal lambs.

Anesthetics, Dissociative ; Animals ; Cardiopulmonary Bypass ; methods ; Female ; Fentanyl ; administration & dosage ; Fetal Heart ; surgery ; Goats ; surgery ; Ketamine ; administration & dosage ; Pregnancy ; Vecuronium Bromide ; administration & dosage

Ketamine hydrochloride is a phencyclidine derivatives and dissociative anesthetics. Ketamine induce the pulmonary vasoconetrietion in vivo. This study was designed to deter- mine the direct effect of the ketamine on the rabbit pulmonary artery in vitro. Isolated pulmonary artery was precontracted with norepinephrine (NE) 10-7M in the 20 ml organ bath. Concentration of ketamine was gradually increased 10-5M, 10 4M and 10-3M at 10 minutes intervals. I divided forty three experimental speeimens into 5 groups : pulmonary artery with and without endothelium, pretreated with indomethacin, nitrow-L-arginine methyl ester(L-NAME) and methylene blue. The results were as follows : 1. Norepinephrine precontracted pulmonary arterial tone wss significantly decreased by ketamine(10-3M), and the relaxing percent were 81.0 19.3, 60.6 55.4 (Mean S.D.) in unrubbed and rubbed endothelium, respectively (p<0.05). 2. The changes of vascular tone in denuding and intact groups were not significantly different. 3. Vasorelaxation induced by ketamine was not related with nitric oxide(NO) synthase, cyclooxygenase and soluble guanylate cyclase. Ketamine induce relaxation of the rabbit pulmonary artery, especially at 10-3 M concentra- tion. The relaxing effect was not related with endothelium presence, nitric oxide synthase, cyclooxygenase and soluble guanylate cyclase pathways. This data suggest that the relaxing effect of ketamine was not associated with endothelium, Nitric oxide, prostacyclin and cyclic guanosinemonophosphate.
Anesthetics, Dissociative ; Arteries ; Baths ; Endothelium ; Epoprostenol ; Guanylate Cyclase ; Indomethacin ; Ketamine* ; Methylene Blue ; NG-Nitroarginine Methyl Ester ; Nitric Oxide ; Nitric Oxide Synthase ; Norepinephrine ; Phencyclidine ; Prostaglandin-Endoperoxide Synthases ; Pulmonary Artery ; Relaxation ; Vasodilation

Ketamine is a noncompetitive NMDA receptor antagonist and comes into being a new problem of drug abuse. It can cause a certain extent of hallucination, which makes ketamine be abused in the casinos. The paper reviews the pharmacological and toxicology characteristic of Ketamine, the possible physiological mechanism and the methods for detecting Ketamine abuse.
Anesthetics, Dissociative/toxicity* ; Cerebral Cortex/drug effects* ; Humans ; Illicit Drugs ; Ketamine/toxicity* ; Mental Disorders/chemically induced* ; Receptors, Dopamine/drug effects* ; Receptors, N-Methyl-D-Aspartate/drug effects* ; Substance Abuse Detection/methods* ; Substance-Related Disorders/prevention & control*

Ketamine is a phencyclidine derivative acting primarily as a noncompetitive antagonist of N-methyl-D-aspartate (NMDA) excitatory glutamate receptors. As a common intravenous anaesthetic in clinic, it is also increasingly abused because of its hallucination and addiction effects. Based on the pharmacological and toxicologic characteristics of ketamine and the acknowledged addiction mechanism of other abused drugs, this article reviews the possible addiction mechanism of the ketamine in the aspects of its enhanced effects and reward systems, the anatomic structures, the related receptors and the individual differences.
Anesthetics, Dissociative/adverse effects* ; Animals ; Brain/drug effects* ; Humans ; Illicit Drugs ; Ketamine/adverse effects* ; Mental Disorders/chemically induced* ; Rats ; Receptors, Dopamine/drug effects* ; Receptors, N-Methyl-D-Aspartate/drug effects* ; Substance-Related Disorders

OBJECTIVE: To investigate the toxicokinetics profiles of ketamine and its main metabolite norketamine in rabbits. METHODS: The rabbits were administered orally the hydrochloride of ketamine with a dose of 0.15 g/kg. The serum and urine samples were collected before administration and at different time points after drug administration. The concentrations of ketamine and norketamine were determined by GC-NPD and GC-MS. Compartment model and toxicokinetics parameters were simulated and calculated by WinNorLin program. Changes of important vital signs of rabbits were recorded during the experiment. RESULTS: The mean serum concentration-time profile of ketamine and norketamine were fitted to a two-compartment open model with first order kinetics. The kinetic equation of ketamine and norketamine were p(t) = 121.760 e(-0.0025t) +0.980 e(-0.002t) +4.579 e(-0.021 t) and p(t) = 640.919 e(-0.03 t) +1.023 e(-0.001 t) +9.784 e (-0.031 t), respectively. The peak time and the peak concentration of ketamine in serum were (40.950 +/- 12.098) min and (9.015 +/- 1.344) microg/mL, respectively. The elimination half-time of ketamine in rabbits was (430.370 +/- 28.436) min. The serum and urine showed a middle relation in concentrations of ketamine during 30-240 min after drug administration. After oral administration ketamine to rabbits, the toxic symptom on the rabbits occurred at 30 min and disappeared after 120 min. CONCLUSION The toxicokinetics parameters and kinetic equation of ketamine and norketamine in rabbits may provide the theoretical basis for forensic identification of reasonable specimen collection and inferring the time of oral administration ketamine from the ketamine concentration in serum.
Administration, Oral ; Anesthetics, Dissociative/toxicity* ; Animals ; Blood Pressure/drug effects* ; Gas Chromatography-Mass Spectrometry/methods* ; Heart Rate/drug effects* ; Ketamine/urine* ; Male ; Perceptual Disorders/etiology* ; Rabbits ; Random Allocation ; Time Factors

The effects of ketamine on transient outward potassium current (I(to)) of isolated human atrial myocytes were investigated to understand the mechanism of part of its effects by whole-cell patch-clamp. Atrial myocytes were enzymatically isolated from specimens of human atrial appendage obtained from patients under going cardiac valve displacing. Ito is recorded in voltage-clamp modes using the patch-clamp technique at room temperature. Currents signals were recorded by an Axopatch 200B amplifier with the Digidata 1322A-pClamp 9.0 data acquisition system. Ketamine decreased I(to) of human atrial myocytes in a dose-dependent manner. The current-voltage curve was significantly lowered, 30, 100, 300, and 1000 micromol x L(-1) ketamine decreased respectively I(to) current density about (13.62 +/- 0.04)%, (38.92 +/- 0.05)%, (72.24 +/- 0.10)% and (83.84 +/- 0.05)% at the potential of 50 mV, with an IC50 of 121 micromol x L(-1). The I(to) activation curve, inactivation curve and the recovery curve were not altered by ketamine. So, ketamine concentration-dependently decreased I(to) of human atrial myocytes.
Adolescent ; Adult ; Aged ; Anesthetics, Dissociative ; administration & dosage ; pharmacology ; Dose-Response Relationship, Drug ; Female ; Heart Atria ; cytology ; Humans ; Ketamine ; administration & dosage ; pharmacology ; Male ; Middle Aged ; Myocytes, Cardiac ; cytology ; drug effects ; physiology ; Patch-Clamp Techniques ; Potassium Channels ; drug effects ; Young Adult

OBJECTIVETo observe the effect of orexin-A on the recovery and cognitive function of aged rats after ketamine anesthesia.

METHODSFifty-five aged rats were divided randomly into control group, model control group, 1 nmol/L Orexin-A group, and 4 nmol/L Orexin-A group. In the latter 3 groups, the rats received an intraperitoneal injection of ketamine at 100 mg/kg, and normal saline was injected in the control group. Ten minutes after the injections, the rats received intraventricular injections of artificial cerebrospinal fluid (control and model control group) or of 10 microl 1 or 4 nmol/L Orexin-A as indicated. The behavioral changes of the rats were assessed by the duration of loss of righting reflex (LORR). Electroencephalogram (EEG) recordings were used to evaluate the changes in rat brain activity by comparison of the percent of sigma wave in EEG before and after the intraventricular injections. Morris water maze was used to test the learning and spatial localization abilities of the rats.

RESULTSKetamine resulted in obvious impairment of learning and memory abilities of the aged rats. Orexin-A at 4 nmol/L induced significant decrease in the duration of LORR and marked reduction of sigma activities in anesthetic rats (P<0.05), and obviously improved the learning and spatial localization abilities of the rats after anesthesia (P<0.05).

CONCLUSIONOrexin-A can promote the recovery and improve the cognitive function of aged rats after ketamine anesthesia.

Aging ; Anesthesia Recovery Period ; Anesthetics, Dissociative ; Animals ; Cognition ; drug effects ; Delayed Emergence from Anesthesia ; prevention & control ; Intracellular Signaling Peptides and Proteins ; pharmacology ; Ketamine ; Male ; Neuropeptides ; pharmacology ; Orexins ; Random Allocation ; Rats ; Rats, Sprague-Dawley