Cocaethylene and heart disease during murine AIDS.
Cocaethylene is an active cocaine metabolite believed to play a causative role in the increased incidence of sudden cardiac death in individuals who co-administer alcohol and cocaine. Prolonged and excessive abuse of cocaine and alcohol will result in marked alteration of host immunity to increased susceptibility to infection. To test the chronic direct effect of cocaethylene on the heart function, a conductance catheter system (CCS) was used in vivo in this study. To test whether cocaethylene injection exacerbates coxsackievirus B3 (CVB3) or cytomegalovirus (CMV) cardiomyopathy during murine AIDS, female C57BL/6 mice were infected with LP-BM5 retrovirus and superinfected with CVB3 or CMV. Daily, mice were injected intraperitoneally with cocaethylene in 0.9% saline solution (concentration increased gradually from 15 to 25 mg/ml). Histopathology of heart tissue was analyzed in all groups, and cytokines of spleen were measured in the CMV-infected groups. Results showed there was little effect on the cardiovascular system after cocaethylene injection. Cocaethylene injection during murine retrovirus infection greatly exacerbated the pathogenesis of CVB3 or CMV infection, whereas CMV-infected mice showed relatively moderate cardiac pathology compared with CVB3 infection. Both CMV and retrovirus infection suppressed the Th1 response. Our data suggest that cocaethylene treatment shifts the cytokine balance and suppresses Th1 response particularly, facilitating increased CVB3- or CMV-induced myocarditis.
Liu
Yingying
Y
Health Promotion Sciences, College of Public Health, University of Arizona, Tucson 85724, USA.
Montes
Sergio
S
Zhang
Dongqin
D
Sepúlveda
Ramón Tomas
RT
Yu
Qianli
Q
Zhang
Jin
J
Larson
Douglas F
DF
Watson
Ronald Ross
RR
D000818:Animals; D006328:Cardiac Catheterization; D003042:Cocaine / Q000031:analogs & derivatives* / Q000633:toxicity*; D003384:Coxsackievirus Infections / Q000150:complications / Q000473:pathology; D016207:Cytokines / Q000096:biosynthesis; D003586:Cytomegalovirus Infections / Q000150:complications / Q000473:pathology; D018765:Dopamine Uptake Inhibitors / Q000633:toxicity*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006321:Heart / Q000503:physiopathology / Q000821:virology; D006331:Heart Diseases / Q000139:chemically induced* / Q000473:pathology*; D006439:Hemodynamics / Q000187:drug effects; D015227:Lipid Peroxidation / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D016183:Murine Acquired Immunodeficiency Syndrome / Q000150:complications / Q000473:pathology*; D009206:Myocardium / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D016207:Cytokines; D018765:Dopamine Uptake Inhibitors; C066444:cocaethylene; D003042:Cocaine