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

• Published in: PloS one Vol. 12; no. 6; p. e0179129
• Main Authors: Rorabaugh, Boyd R, Seeley, Sarah L, Stoops, Thorne S, D'Souza, Manoranjan S
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 02.06.2017; Public Library of Science (PLoS)
• Subjects: AKT protein; Animals; Biology and Life Sciences; Cardiomyocytes; Care and treatment; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - adverse effects; Chlorides; Dosage and administration; Drug abuse; Exposure; Extracellular signal-regulated kinase; Female; Females; Gender differences; Heart; Heart - drug effects; Heart - physiopathology; Heart attack; Heart diseases; Hypersensitivity; Injuries; Ischemia; Male; Medicine and Health Sciences; Methamphetamine; Methamphetamine - administration & dosage; Methamphetamine - adverse effects; Muscle contraction; Myocardial Contraction - drug effects; Myocardial infarction; Myocardial Infarction - etiology; Myocardial Infarction - pathology; Myocardial Infarction - physiopathology; Myocardial Ischemia - complications; Myocardial Ischemia - pathology; Myocardial Ischemia - physiopathology; Myocardium - pathology; People and Places; Phosphorylation; Physical Sciences; Protein kinase; Protein kinase C; Protein kinases; Rats; Rats, Sprague-Dawley; Recovery; Risk; Rodents; Sex; Sex Factors; Sexual behavior; Staining; Triphenyltetrazolium chloride; Xenografts; United States > US; Ohio
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0179129

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. 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. 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. 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.