Ecstasy produces left ventricular dysfunction and oxidative stress in rats.
Sylvia K Shenouda, Kevin C Lord, Elizabeth McIlwain, Pamela A Lucchesi, Kurt J Varner
Cardiovascular research September 1, 2008 DOI: 10.1093/cvr/cvn129 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Controlled animal experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | 3 4-methylenedioxymethamphetamine (ecstasy; MDMA) |
| Dose | 9 mg/kg i.v. for 4 days, four binges separated by a 10 day drug-free period |
| Duration | Four binges of 4 days each, separated by 10-day drug-free periods |
| Measures | Echocardiography, pressure-volume conductance catheters, Fura-2 (intracellular calcium measurement), nitrotyrosine content, proteomic analysis |
| Topics | MDMA |
| Key findings | Repeated binge ecstasy administration in rats produced eccentric left ventricular dilation and diastolic dysfunction without altering in vivo systolic function, alongside weaker myocyte contractions and impaired intracellular calcium handling. The authors attribute these effects to oxidative stress, evidenced by increased nitrotyrosine content and nitration of contractile, mitochondrial, and calcium-handling proteins, and conclude that ecstasy has the potential to cause serious cardiac toxicity and ventricular dysfunction. |
Abstract
Our aim was to determine whether the repeated, binge administration of 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) produces structural and/or functional changes in the myocardium that are associated with oxidative stress. Echocardiography and pressure-volume conductance catheters were used to assess left ventricular (LV) structure and function in rats subjected to four ecstasy binges (9 mg/kg i.v. for 4 days, separated by a 10 day drug-free period). Hearts from treated and control rats were used for either biochemical and proteomic analysis or the isolation of adult LV myocytes. After the fourth binge, treated hearts showed eccentric LV dilation and diastolic dysfunction. Systolic function was not altered in vivo; however, the magnitude of the contractile responses to electrical stimulation was significantly smaller in myocytes from rats treated in vivo with ecstasy compared with myocytes from control rats. The magnitude of the peak increase in intracellular calcium (measured by Fura-2) was also significantly smaller in myocytes from ecstasy-treated vs. control rats. The relaxation kinetics of the intracellular calcium transients were significantly longer in myocytes from ecstasy-treated rats. Ecstasy significantly increased nitrotyrosine content in the left ventricle. Proteomic analysis revealed increased nitration of contractile proteins (troponin-T, tropomyosin alpha-1 chain, myosin light polypeptide, and myosin regulatory light chain), mitochondrial proteins (Ub-cytochrome-c reductase and ATP synthase), and sarcoplasmic reticulum calcium ATPase. The repeated binge administration of ecstasy produces eccentric LV dilation and dysfunction that is accompanied by oxidative stress. These functional responses may result from the redox modification of proteins involved in excitation-contraction coupling and/or mitochondrial energy production. Together, these results indicate that ecstasy has the potential to produce serious cardiac toxicity and ventricular dysfunction.
Comparable studies
Other preclinical and animal studies on MDMA, most cited first.
Citations in the library
Cited by 10
- The risk of chronic psychedelic and MDMA microdosing for valvular heart disease Journal of Psychopharmacology August 12, 2023
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- Protective effects of vitamin E and quercetin against MDMA-induced cardiac and hematological dysfunction in male wistar rats. Pflügers Archiv: European Journal of Physiology April 23, 2026
- Cardiac Consequences Associated with Psychedelic Use: A Systematic Review of Lysergic Acid Diethylamide, 3,4-Methylenedioxymethamphetamine, and 5-Hydroxytryptamine 2B-Mediated Valvular Heart Disease. Pharmacopsychiatry February 5, 2026
- MDMA Induced Cardio-toxicity and Pathological Myocardial Effects: A Systematic Review of Experimental Data and Autopsy Findings. Cardiovascular toxicology December 2019
and 5 more in the library
Cites 13
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- 'Eve' and 'Ecstasy'. A report of five deaths associated with the use of MDEA and MDMA JAMA March 27, 1987
- Pathology of deaths associated with "ecstasy" and "eve" misuse. Journal of Clinical Pathology February 1, 1996
- α-Lipoic acid prevents 3,4-methylenedioxy-methamphetamine (MDMA)-induced neurotoxicity Neuroreport November 1, 1999
- Superoxide radicals mediate the biochemical effects of methylenedioxymethamphetamine (MDMA): Evidence from using CuZn‐superoxide dismutase transgenic mice Synapse October 1, 1995
and 8 more in the library