Cardiotoxicity induced in mice by long term ketamine and ketamine plus alcohol treatment.
W M Chan, Y Liang, Maria S M Wai, Angela S M Hung, D T Yew
Toxicology Letters November 30, 2011 DOI: 10.1016/j.toxlet.2011.09.008 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal experimental study Peer reviewed |
|---|---|
| Population | 1-month-old ICR mice |
| Interventions | Ketamine Ethanol |
| Dose | Ketamine 30 mg/kg intraperitoneally; 0.5 ml of 10% ethanol orally |
| Duration | Ketamine for 6, 16, or 28 weeks; ethanol for the last 4 weeks of the 28-week group |
| Measures | Electrocardiogram (ECG), troponin, lactate dehydrogenase |
| Topics | Esketamine Ketamine |
| Key findings | Long-term ketamine exposure in mice was associated with signs of cardiac damage: ST elevations appeared in 30% of mice from 6 weeks onward, with increased serum troponin and lactate dehydrogenase-positive cardiac cells. Adding daily ethanol for the last 4 weeks of the 28-week ketamine regimen worsened cardiac function, indicated by a further rise in troponin. |
Abstract
Increased use of ketamine as a recreational drug in rave party has raised lots of social concerns. Although its toxicity on the central nervous system (CNS) and urinary system had been reported, its potential adverse effects on the heart is still not addressed. Using our long term ketamine addiction model in which, 1-month-old ICR mice were given ketamine intraperitoneally (i.p. 30 mg/kg) for different study periods (6 weeks, 16 weeks and 28 weeks). The electrocardiogram (ECG) and the level of troponin as well as the presence of lactate dehydrogenase were used together to determine the cardiac function of mice. ST elevations were observed in 30% of mice from 6 weeks onwards. Concomitant increase in troponin in serum and presence of lactate dehydrogenase positive cardiac cells were taken together to indicate cardiac damages. The potential interactive effects of alcohol (ethanol) and ketamine were also addressed and 0.5 ml of 10% ethanol was administrated additionally to the mice daily and orally for the last 4 weeks in the 28-week long-term ketamine treated animals. The cardiac functions of these mice deteriorated more severely as indicated by further rise in troponin levels. In addition, high number of lactate dehydrogenase positive cardiac cells and abnormal ECGs in both ketamine and ketamine plus alcohol treated models also gave coherent conclusions.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |
Citations in the library
Cited by 4
- Brain damages in ketamine addicts as revealed by magnetic resonance imaging Frontiers in Neuroanatomy May 22, 2014
- Ketamine as Antidepressant? Current State and Future Perspectives Current Neuropharmacology August 1, 2013
- The effects of sub-anesthetic ketamine plus ethanol on behaviors and apoptosis in the prefrontal cortex and hippocampus of adolescent rats. Pharmacology, Biochemistry, and Behavior July 23, 2019
- The interactive effects of ketamine and ethanol on dopamine expression in the ventral tegmental area of rats. Neuropsychiatric Disease and Treatment 2018