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Nonuniform cardiac denervation observed by 11C-meta-hydroxyephedrine PET in 6-OHDA-treated monkeys.
Joers, Valerie; Seneczko, Kailie; Goecks, Nichole C; Kamp, Timothy J; Hacker, Timothy A; Brunner, Kevin G; Engle, Jonathan W; Barnhart, Todd E; Nickles, R Jerome; Holden, James E; Emborg, Marina E.
Afiliação
  • Joers V; Preclinical Parkinson's Research Program, Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, Wisconsin, United States of America.
PLoS One ; 7(4): e35371, 2012.
Article em En | MEDLINE | ID: mdl-22539969
ABSTRACT
Parkinson's disease presents nonmotor complications such as autonomic dysfunction that do not respond to traditional anti-parkinsonian therapies. The lack of established preclinical monkey models of Parkinson's disease with cardiac dysfunction hampers development and testing of new treatments to alleviate or prevent this feature. This study aimed to assess the feasibility of developing a model of cardiac dysautonomia in nonhuman primates and preclinical evaluations tools. Five rhesus monkeys received intravenous injections of 6-hydroxydopamine (total dose 50 mg/kg). The animals were evaluated before and after with a battery of tests, including positron emission tomography with the norepinephrine analog (11)C-meta-hydroxyephedrine. Imaging 1 week after neurotoxin treatment revealed nearly complete loss of specific radioligand uptake. Partial progressive recovery of cardiac uptake found between 1 and 10 weeks remained stable between 10 and 14 weeks. In all five animals, examination of the pattern of uptake (using Logan plot analysis to create distribution volume maps) revealed a persistent region-specific significant loss in the inferior wall of the left ventricle at 10 (P<0.001) and 14 weeks (P<0.01) relative to the anterior wall. Blood levels of dopamine, norepinephrine (P<0.05), epinephrine, and 3,4-dihydroxyphenylacetic acid (P<0.01) were notably decreased after 6-hydroxydopamine at all time points. These results demonstrate that systemic injection of 6-hydroxydopamine in nonhuman primates creates a nonuniform but reproducible pattern of cardiac denervation as well as a persistent loss of circulating catecholamines, supporting the use of this method to further develop a monkey model of cardiac dysautonomia.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidopamina / Compostos Radiofarmacêuticos / Efedrina / Coração Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Oxidopamina / Compostos Radiofarmacêuticos / Efedrina / Coração Tipo de estudo: Diagnostic_studies / Prognostic_studies Limite: Animals Idioma: En Revista: PLoS One Assunto da revista: CIENCIA / MEDICINA Ano de publicação: 2012 Tipo de documento: Article País de afiliação: Estados Unidos