Abstract
BackgroundWe 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.MethodsAdult 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.ResultsHearts 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.ConclusionsExposure 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.
Highlights
Methamphetamine is one of the most commonly abused illicit stimulants in the United States
Myocardial protein kinase C-ε expression, Akt phosphorylation, and ERK phosphorylation were unaffected by adult exposure to methamphetamine
Methamphetamine induces sex-dependent hypersensitivity to ischemic injury in the heart attack might be at risk of more extensive myocardial injury if they have a recent history of methamphetamine abuse
Summary
Methamphetamine is one of the most commonly abused illicit stimulants in the United States. Hearts from adult female rats that had been prenatally exposed to methamphetamine exhibited significantly larger infarcts following an ischemic insult compared to hearts from adult females that were prenatally exposed to saline [11] This was accompanied by changes in proteins (PKC-ε expression and Akt phosphorylation) that are known to protect the heart from ischemic injury [11]. Prenatal methamphetamine had no effects on infarct size, PKC-ε expression, or Akt phosphorylation in their adult male littermates [11] These data provide evidence that prenatal exposure to methamphetamine leads to sex-dependent changes in cardioprotective proteins and increased myocardial sensitivity to ischemic injury that persists into adulthood. The goal of this study was to determine whether methamphetamine exposure during adulthood sensitizes the heart to ischemic injury
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