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Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart

BACKGROUND: We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during...

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Autores principales: Rorabaugh, Boyd R., Seeley, Sarah L., Stoops, Thorne S., D’Souza, Manoranjan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456396/
https://www.ncbi.nlm.nih.gov/pubmed/28575091
http://dx.doi.org/10.1371/journal.pone.0179129
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author Rorabaugh, Boyd R.
Seeley, Sarah L.
Stoops, Thorne S.
D’Souza, Manoranjan S.
author_facet Rorabaugh, Boyd R.
Seeley, Sarah L.
Stoops, Thorne S.
D’Souza, Manoranjan S.
author_sort Rorabaugh, Boyd R.
collection PubMed
description BACKGROUND: We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. METHODS: Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. RESULTS: Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. CONCLUSIONS: Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse.
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spelling pubmed-54563962017-06-12 Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart Rorabaugh, Boyd R. Seeley, Sarah L. Stoops, Thorne S. D’Souza, Manoranjan S. PLoS One Research Article BACKGROUND: We previously reported that adult female, but not male rats that were prenatally exposed to methamphetamine exhibit myocardial hypersensitivity to ischemic injury. However, it is unknown whether hypersensitivity to ischemic injury develops when rats are exposed to methamphetamine during adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury. METHODS: Adult male and female rats received daily injections of methamphetamine (5 mg/kg) or saline for 10 days. Their hearts were isolated on day 11 and subjected to a 20 min ischemic insult on a Langendorff isolated heart apparatus. Cardiac contractile function was measured by an intraventricular balloon, and infarct size was measured by triphenyltetrazolium chloride staining. RESULTS: Hearts from methamphetamine-treated females exhibited significantly larger infarcts and suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, methamphetamine had no effect on infarct size or contractile recovery in male hearts. Subsequent experiments demonstrated that hypersensitivity to ischemic injury persisted in female hearts following a 1 month period of abstinence from methamphetamine. Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine. CONCLUSIONS: Exposure of adult rats to methamphetamine sex-dependently increases the extent of myocardial injury following an ischemic insult. These data suggest that women who have a heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse. Public Library of Science 2017-06-02 /pmc/articles/PMC5456396/ /pubmed/28575091 http://dx.doi.org/10.1371/journal.pone.0179129 Text en © 2017 Rorabaugh et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Rorabaugh, Boyd R.
Seeley, Sarah L.
Stoops, Thorne S.
D’Souza, Manoranjan S.
Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title_full Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title_fullStr Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title_full_unstemmed Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title_short Repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
title_sort repeated exposure to methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the adult rat heart
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5456396/
https://www.ncbi.nlm.nih.gov/pubmed/28575091
http://dx.doi.org/10.1371/journal.pone.0179129
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