Cocaine Increases Mortality and Cardiac Mass in a Murine Transgenic Model of Acquired Immune Deficiency Syndrome

Lab Invest. 2003 Jul;83(7):983-9. doi: 10.1097/01.lab.0000075555.93242.f2.

Abstract

Cardiac dysfunction in AIDS is an important problem. Cocaine is an epidemic associated with sudden death, cardiac dysfunction, and congestive heart failure. Cocaine use and HIV infection frequently coexist in the same patient, yet the combined impact of both is poorly understood. The present study uses cocaine treatment of an established murine AIDS transgenic model (NL4-3Delta gag/pol; TG) to define the combined effects of AIDS and cocaine on cardiac pathophysiology. To determine the effects of cocaine and HIV-1 proteins on mortality, wild-type and NL4-3Delta gag/pol mice received saline or cocaine via continuous infusion by Alzet osmotic pumps for 28 days (chronic). Acute cocaine administration (10 days; 40 mg/kg/day) was used to study the nonlethal effects of cocaine in TGs. Echocardiograms and single time point electrocardiograms were performed at the termination of each experiment. Hearts were removed and examined histopathologically. Chronic cocaine treatment (80 mg/kg/day; 28 days) markedly decreased median survival in both wild-type and TG; however, TG survival was significantly more decreased. In acute studies, TG echocardiographic changes included increased left ventricular mass and increased left ventricular fractional shortening compared with all cohorts. Electrocardiographic changes were absent among the groups. Histopathologically, perivascular fibrosis and interstitial fibrosis were evident in cocaine-treated TG. Data suggest that additive cardiac insults (from AIDS and cocaine) result in combined deleterious effects.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acquired Immunodeficiency Syndrome / complications
  • Acquired Immunodeficiency Syndrome / mortality
  • Acquired Immunodeficiency Syndrome / pathology*
  • Animals
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / mortality
  • Cardiomyopathies / pathology*
  • Cocaine / pharmacology*
  • Disease Models, Animal
  • Electrocardiography
  • Female
  • Heart Ventricles / drug effects*
  • Heart Ventricles / pathology*
  • Heart Ventricles / physiopathology
  • Infusion Pumps, Implantable
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Myocardium / pathology
  • Organ Size / drug effects
  • Survival Rate
  • Ventricular Dysfunction, Left / chemically induced
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / virology

Substances

  • Cocaine