Rorabaugh Boyd R, Seeley Sarah L, Stoops Thorne S, D'Souza Manoranjan S
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, Ohio Northern University, Ada, Ohio, United States of America.
PLoS One. 2017 Jun 2;12(6):e0179129. doi: 10.1371/journal.pone.0179129. eCollection 2017.
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.
我们之前报道过，产前暴露于甲基苯丙胺的成年雌性大鼠，而非雄性大鼠，对缺血性损伤表现出心肌超敏反应。然而，尚不清楚大鼠成年期暴露于甲基苯丙胺时是否会发生对缺血性损伤的超敏反应。本研究的目的是确定成年期暴露于甲基苯丙胺是否会使心脏对缺血性损伤敏感。
成年雄性和雌性大鼠每天注射甲基苯丙胺（5毫克/千克）或生理盐水，持续10天。在第11天分离它们的心脏，并在Langendorff离体心脏装置上进行20分钟的缺血性损伤。通过心室内球囊测量心脏收缩功能，通过氯化三苯基四氮唑染色测量梗死面积。
与生理盐水处理的雌性大鼠的心脏相比，甲基苯丙胺处理的雌性大鼠的心脏梗死面积明显更大，且缺血后收缩功能的恢复受到抑制。相比之下，甲基苯丙胺对雄性大鼠心脏的梗死面积或收缩功能恢复没有影响。随后的实验表明，在戒除甲基苯丙胺1个月后，雌性大鼠心脏对缺血性损伤的超敏反应仍然存在。成年期暴露于甲基苯丙胺对心肌蛋白激酶C-ε表达、Akt磷酸化和ERK磷酸化没有影响。
成年大鼠暴露于甲基苯丙胺会依性别增加缺血性损伤后的心肌损伤程度。这些数据表明，近期有甲基苯丙胺滥用史的女性心脏病发作时，可能面临更广泛心肌损伤的风险。
