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Tempol attenuates methamphetamine‐induced left ventricular (LV) dysfunction
Author(s) -
Lord Kevin C,
Shenouda Sylvia,
McIlwain Elizabeth,
Pollman Megan,
Lucchesi Pam,
Varner Kurt
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a801
Subject(s) - meth , methamphetamine , medicine , ejection fraction , superoxide , superoxide dismutase , saline , diastole , cardiology , endocrinology , heart failure , chemistry , blood pressure , oxidative stress , enzyme , biochemistry , monomer , organic chemistry , acrylate , polymer
The elicit use of methamphetamine (METH) is associated with LV dilation and dysfunction. While the underlying mechanisms are largely unknown, our data with dihydroethidium staining led us to hypothesize that increased superoxide plays an important role in METH‐induced LV dysfunction. Male Sprague‐Dawley rats were treated i.v. with saline (0.9%, n=7), METH (3 mg/kg, n=7), or METH (3 mg/kg) plus the superoxide dismutase mimetic, Tempol (2.5 nM in drinking water, n=7). Saline and METH were administered 2X/d for 4 d, followed by a 10‐d drug‐free period (“binge”). 4 binges were administered. Cardiac structure and function were monitored echocardiographically (ECHO) before the 1 st and after the 2 nd and 4 th binges. ECHO showed evidence of LV dilation, systolic and diastolic dysfunction after binge 2. After binge 4, Millar pressure‐volume catheters showed that compared to control, METH significantly increased end diastolic volume (EDV, 185±13 μl vs 286±12 μl), increased Tau, and decreased ejection fraction (EF). Tempol prevented METH‐induced changes in EDV (154±13 μl) and EF, but not Tau. We conclude that METH produces LV dilation and systolic dysfunction by increasing superoxide levels; however, increased superoxide does not appear to contribute to METH‐induced diastolic dysfunction. Support AHA 0555769B, NIH P20‐RR018766.