Ecstasy produces left ventricular dysfunction and oxidative stress in rats.
OBJECTIVE
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.


RESULTS
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.


CONCLUSIONS
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.
Shenouda
Sylvia K
SK
Department of Pharmacology and Experimental Therapeutics, The Cardiovascular Center, Louisiana State University Health Sciences Center, 1901 Perdido Street P7-1, New Orleans, LA 70112, USA.
Lord
Kevin C
KC
McIlwain
Elizabeth
E
Lucchesi
Pamela A
PA
Varner
Kurt J
KJ
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D003971:Diastole; D004108:Dilatation, Pathologic; D004558:Electric Stimulation; D006213:Hallucinogens / Q000008:administration & dosage / Q000633:toxicity*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007275:Injections, Intravenous; D007700:Kinetics; D008297:Male; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013599:Systole; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism; D014463:Ultrasonography; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced* / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology
D006213:Hallucinogens; D009124:Muscle Proteins; C002744:3-nitrotyrosine; D014443:Tyrosine; D018817:N-Methyl-3,4-methylenedioxyamphetamine