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Cardiac Toxicity of Cocaine: from Myocardial Depression to Cardiomyopathy

  • Ju-Feng Wang
  • Matthew E. Sullivan
  • Jiangyong Min
  • James P. Morgan
Part of the Progress in Experimental Cardiology book series (PREC, volume 5)

Abstract

This study was designed to determine the toxicity of cocaine on heart and other organ tissues. To investigate this, in study one, BALB/C mice were injected daily with either saline or one of three doses of cocaine (ip): 10mg/kg, 30mg/kg, or 50mg/kg. Hemodynamic parameters, hepatic biochemical changes, heart and liver apoptosis, and tumor necrosis factor (TNF-α) levels were analyzed after cocaine administration. After administration of cocaine, left ventricular pressure decreased among the three dose groups. Also, +dP/dt was decreased from 7598 mmHg/s in the saline group to 5448, 5198, and 5042 mmHg/s, respectively in the 10, 30, and 50mg/kg groups. Moreover, histopathology demonstrated that hepatocyte necrosis could be observed in the liver. Neutrophils, lymphocytes, and cellular debris surrounded the central area of necrosis in the three cocaine-treated groups. Also, inflammatory cell infiltration and eosinophilic contraction bands were visible in the 50/kgmg groups hearts. TdT-mediated dUTP nick end-labeling (TUNEL) staining and DNA ladder analysis indicated that cocaine caused apoptosis in the heart and liver. The ratio of TUNEL and Hoechst 33258 staining nuclei from the livers were 6.1 ± 2.3, 11.0 ± 2.7 and 12.3 ± 4.2%, respectively in the 10, 30, and 50mg/kg cocaine groups. However, in the heart apoptosis occurred only in the high dose group and the apoptotic percentage was 5.7 ± 1.4%. TNF-α levels were 1.75 ± 0.91 ng/g (saline); 4.13 ± 0.36, 5.03 ± 0.36, and 5.77 ± 0.67 ng/g respectively in the 10, 30, and 50mg/kg cocaine groups, significantly higher in all cocaine-treated mice hearts compared to saline control (p < 0.05). Moreover, in the liver the content of TNF-α was increased from 621.8 ± 73 in the saline group to 867.2 ± 72, 940.8 ± 61, and 1032.8 ± 69 (ng/g) among the three dose groups. However, RT-PCR study showed that there was no significant difference in the levels of mRNA of TNF-α between cocaine and saline groups both in the heart and liver. These results suggest that cocaine impaired cardiac function and caused liver necrosis. In addition, cocaine triggered programmed cell death and induced the production of TNF-α in mouse myocardium and liver. In study two, we investigated whether cocaine can exacerbate viral myocarditis or increase its incidence. Male BALB/c mice were divided into eight groups: saline control, encephalomyocarditis virus (EMCV), Cocaine 10mg/kg (Coc-10), Cocaine 30mg/kg (Coc-30), Cocaine 50mg/kg (Coc-50), EMCV+Coc-10, EMCV+Coc-30, and EMCV+Coc-50. After inoculation with EMCV, the mice were treated daily with cocaine or saline for 90 days. Mice were sacrificed at different days after EMCV inoculation. Mortality was recorded and myocarditis severity was evaluated. The mortality of the myocarditis mice treated with cocaine increased significantly, from 22% (EMCV) to 25.7% (Coc-10+EMCV), 41.4% (Coc-30+EMCV), and 51.4% (Coc-50+EMCV) (p<0.05). The incidence and severity of inflammatory cell infiltration and myocardial lesions was higher in infected mice exposed to cocaine. In conclusion, these results suggested that the liver is more sensitive than the heart to cocaine toxicity, and induction of apoptosis or TNF-α may be an important mechanism related to cocaine s toxicity. Also, exposure to cocaine significantly increased the mortality and exacerbated the severity of viral myocarditis. This enhancing effect of cocaine on viral myocarditis may relate to catecholamines.

Key words

cocaine apoptosis TNF-α viral myocarditis mouse 

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Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Ju-Feng Wang
    • 1
  • Matthew E. Sullivan
    • 1
  • Jiangyong Min
    • 1
  • James P. Morgan
    • 1
  1. 1.Cardiovascular Division, Beth Israel Deaconess Medical CenterHarvard Medical SchoolBostonUSA

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