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Ecstasy produces left ventricular dysfunction and oxidative stress in rats
Sylvia K Shenouda1, Kevin C Lord, Elizabeth McIlwain
1Department of Pharmacology and Experimental Therapeutics, The Cardiovascular Center, Louisiana State University Health Sciences Center, 1901 Perdido Street P7-1, New Orleans, LA 70112, USA.
Cardiovascular Research
|May 23, 2008
Summary
Repeated binge use of ecstasy (MDMA) causes cardiac changes, including left ventricular dilation and dysfunction, linked to oxidative stress and protein damage. This suggests potential for serious heart toxicity from ecstasy.
Area of Science:
- Cardiovascular Physiology
- Toxicology
- Biochemistry
Background:
- 3,4-methylenedioxymethamphetamine (ecstasy; MDMA) is a recreational drug with known cardiotoxic potential.
- Understanding the specific mechanisms of MDMA-induced cardiac dysfunction is crucial for public health and clinical management.
Purpose of the Study:
- To investigate whether repeated, binge administration of MDMA induces structural and functional changes in the myocardium.
- To determine if these cardiac alterations are associated with oxidative stress.
Main Methods:
- Rats were administered MDMA in a binge pattern (9 mg/kg i.v. for 4 days, with drug-free intervals).
- Left ventricular structure and function were assessed using echocardiography and pressure-volume conductance catheters.
- Cardiac tissue underwent biochemical, proteomic analysis, and myocyte isolation for functional assessments.
Main Results:
- MDMA binge administration resulted in eccentric left ventricular dilation and diastolic dysfunction.
- While in vivo systolic function was unchanged, isolated myocytes showed reduced contractile responses and altered calcium handling.
- Increased nitrotyrosine content and nitration of key contractile and mitochondrial proteins were observed in MDMA-treated hearts.
Conclusions:
- Repeated MDMA binge use leads to cardiac dysfunction and structural changes, characterized by oxidative stress.
- Redox modification of proteins involved in excitation-contraction coupling and mitochondrial function likely underlies these detrimental effects.
- These findings highlight the potential for MDMA to cause significant cardiac toxicity and ventricular dysfunction.