Cardiomyopathy model

P MRS of the open-chested mouse at 4.7T. In a P MRSI study performed on a 9.4-T vertical-bore spectrometer, Flogel et al. were able to map localized energetics in several regions of the heart in a transgenic murine cardiomyopathy model. They found that cardiac dysfunction in the mutant was associated with impaired energy state. 

Kawamura, M., Miyagawa, S., Miki, K., Saito, A., Fukushima, S., Higuchi, T., et al., 2012. Feasibility, safety, and therapeutic efficacy of human induced pluripotent stem cell-derived cardiomyocyte sheets in a porcine ischemic cardiomyopathy model. Circulation 126 (ll(Suppl. 1)), S29-S37. 

Idarubicin inhibits both DNA and RNA polymerase, as well as topoisomerase II. The pharmacokinetics of idarubicin can best be described by a three-compartment model, with an a half-life of 13 minutes, a (3 half-life of 2.4 hours, and a terminal half-life of 16 hours.22 Idarubicin is metabolized to an active metabolite, idarubicinol, which has a half-life of 41 to 69 hours. Idarubicin and idarubicinol are eliminated by the liver and through the bile. Idarubicin has shown clinical activity in the treatment of acute leukemias, chronic myelogenous leukemia, and myelodysplastic syndromes. Idarubicin causes cardiomyopathy at cumulative doses of greater than 150 mg/m2 and produces cumulative cardiotoxic effects with other anthracyclines. Idarubicin is a vesicant and causes red-orange urine, mucositis, mild to moderate nausea and vomiting, and bone marrow suppression. 

Weekes J et al. Bovine dilated cardiomyopathy proteomic analysis of an animal model of human dilated cardiomyopathy Electrophoresis 1999 20 898-906. Doherty NS et al. Analysis of changes in acute phase plasma proteins in an acute inflammatory response and in rheumatoid arthritis using two-dimensional gel electrophoresis. Electrophoresis 1998 19 355-363. 

Liang Q, Carlson EC, Borgerding AJ, Epstein PN. A transgenic model of acetaldehyde overproduction accelerates alcohol cardiomyopathy. J Pharmacol Exp Ther 1999 291 766-772. 

Animal models have established that infections can induce autoimmune disease. For example, coxsackievirus B3 infection of susceptible strains of mice results in inflammation in the heart that resembles the myocarditis and dilated cardiomyopathy that occurs in humans.28 44 The same disease can be induced by injecting mice with cardiac myosin mixed with adjuvant, thereby reproducing the disease in the absence of virus infection, indicating that an active viral infection is not necessary for the development of autoimmune disease.9 29 44 Likewise, a number of autoimmune diseases can be... 

Dewald O, Sharma S, Adrogue J, et al. Downregulation of peroxisome proliferator-activated receptor-alpha gene expression in a mouse model of ischemic cardiomyopathy is dependent on reactive oxygen species and prevents lipotoxicity. Circulation. Jul 19 2005 112(3) 407 15. 

There are also plans to deliver a gene therapy product nonsurgicaUy for the treatment of patients with heart failure. In a controlled trial in a pig model of pacing-induced heart failure, intracoronary delivery of human FGF-4 showed significant improvement in regional cardiac function and a reduction in the size of the heart. If these results translate favorably to humans, FGF-4 gene therapy may be a therapeutic option for patients with cardiomyopathy. 

Bovine dilated cardiomyopathy proteomic analysis of an animal model of human dilated cardiomyopathy. Electrophoresis 20, 898-906. 

Byrne MJ, Kaye DM, Mathis M, et al. Percutaneous mitral annular reduction provides continued benefit in an ovine model of dilated cardiomyopathy. Circulation 2004 110 3088—92. 

Christiansen, S., K. Redman, H. H. Scheld., U. R. Jahn, J. Stypmann, M. Fobker, A. D. Gruber, and D. Hammel. 2002. Adriamycin-induced cardiomyopathy in the dog—An appropriate model for research on partial left ventriculectomy. Journal of Heart and Lung Transplantation 21 783-790. 

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