Cardiac repolarization is prolonged in CD4C/HIV transgenic mice
Judith Brouillettea,b, Scott A. Grandya,b, Paul Jolicoeur c, Céline Fiseta,b
a Research Center, Montreal Heart Institute, 5000 Belanger Street, Montreal, Quebec, Canada H1T 1C8
b Faculty of Pharmacy, University of Montreal, Canada
c Clinical Research Institute of Montreal, Canada
J Mol Cell Cardiol. 2007 May 18; [Epub ahead of print]





Brief Summary:
  • > Pharmacological agents used to treat patients with AIDS have been associated with QT prolongation and result in delayed repolarization. New evidence suggests that delayed repolarization can occur independently of pharmacological therapy. However, the effect of HIV on ventricular repolarization has not been investigated. Therefore, the objective of this study was to characterize cardiac repolarization in a mouse model of human HIV disease. All experiments were conducted on HIV transgenic mice (CD4C/HIV). These mice express the human HIV gene nef in cells of immune system and develop a severe AIDS-like disease that is similar to that observed in humans. ECG was recorded in conscious free moving mice and patch-clamp techniques were used to record action potentials and K+ current densities in single ventricular myocytes. Results showed that the QT interval and action potential duration were significantly prolonged in CD4C/HIV mice compared to wild-type littermates. This delay in repolarization was associated with a significant reduction in outward K+ currents. Echocardiography (Vevo 770 micro-ultrasound, VisualSonics) were similar in CD4C/HIV and littermate control mice. This suggests that the changes in ventricular repolarization were not the result of heart failure or cardiac hypertrophy. Overall, this study shows that repolarization was delayed in CD4C/HIV mice and that this phenotype occurred in the absence of any pharmacological intervention. Thus, it appears that HIV may be responsible for the delayed ventricular repolarization phenotype observed in CD4C/HIV mice.

    NOTE: All echographic studies performed in this paper used the Vevo 770 micro-ultrasound system.