Impact of Prenatal or Adult Exposure to Methamphetamine on the Ischemic Heart

摘要 甲基苯丙胺是美国最常被滥用的非法药物之一。甲基苯丙胺 在18-34岁的成年人中使用最为普遍。值得注意的是，这一年龄段包括 生育年龄。大多数关于产前接触甲基苯丙胺的研究都集中在神经学上。 结果。相反，产前暴露于甲基苯丙胺对成人心血管的影响 系统实际上已经被忽视了。此外，大多数研究考察了甲基苯丙胺对 心脏关注的是目前或最近使用该药物的受试者的急性影响。很少有研究 研究了甲基苯丙胺对患有高血压的人或动物的长期心血管影响 甲基苯丙胺暴露史(产前或成年期)，但不再使用 冰毒。最近的研究表明，产前接触甲基苯丙胺 或在成年早期导致缺血性心脏的性别依赖性变化。雌性老鼠，但不是它们的 在产前或成年早期接触过甲基苯丙胺的男性兄弟姐妹会患上心肌梗死 对缺血损伤的超敏反应。此外，在经历了一段时间后，对缺血的超敏反应仍然存在。 戒毒，表明甲基苯丙胺可能会引起心脏的性别依赖性变化 这是不可逆转的。这些数据表明，患有心脏病的女性患心脏病的风险可能更高。 如果他们在产前暴露于甲基苯丙胺或 在成年初期，即使他们长期戒毒 时间到了。尽管甲基苯丙胺的使用在年轻人中最为普遍，但心脏病发作最常发生在 老年人口。因此，本研究的目的1是确定是否对缺血损伤敏感 在产前或成年早期接触甲基苯丙胺后，会持续到老年阶段 当缺血性心脏病最常见的时候。目标2是确定易感疾病的妊娠期 胎儿期甲基苯丙胺的这种作用。目标3是确定甲基苯丙胺 导致对缺血损伤的性别依赖性过敏。缺血性心脏病是导致死亡的主要原因。 在美国。鉴于滥用甲基苯丙胺的盛行，我们必须了解 产前或成人早期接触甲基苯丙胺对缺血心脏的影响，包括长期影响 在停止使用甲基苯丙胺的受试者身上持续存在的影响。我们预计，拟议的 这项工作将增进我们对产前或成人接触铅的心脏后果的理解。 冰毒。这些数据还将提供对甲基苯丙胺诱导的基因变化的洞察 表达可能是甲基苯丙胺诱导的心肌病、心律失常和其他心脏疾病的基础 因滥用甲基苯丙胺而导致的病理改变。

Abstract Methamphetamine is one of the most commonly abused illicit drugs in the United States. Methamphetamine use is most prevalent among adults 18 – 34 years of age. Notably, this age group includes women of childbearing age. Most studies of prenatal exposure to methamphetamine have focused on neurological outcomes. In contrast, the impact of prenatal exposure to methamphetamine on the adult cardiovascular system has been virtually ignored. In addition, most studies examining the impact of methamphetamine on the heart have focused on acute effects in subjects that were current or recent users of the drug. Few studies have investigated the long term cardiovascular impact of methamphetamine in people or animals that have a history of methamphetamine exposure (prenatal or during adulthood) but are no longer using methamphetamine. Recent work demonstrated that exposure to methamphetamine during the prenatal period or during early adulthood causes sex-dependent changes to the ischemic heart. Female rats, but not their male siblings, that were exposed to methamphetamine prenatally or during early adulthood develop myocardial hypersensitivity to ischemic injury. Furthermore, hypersensitivity to ischemia persists following a period of abstinence from the drug, indicating that methamphetamine may induce sex dependent changes in the heart that are irreversible. These data suggest that women who have heart attacks may be at risk of more extensive myocardial injury if they were exposed to methamphetamine during the prenatal period or during early adulthood, even if they have remained abstinent from the drug for a prolonged period of time. Although methamphetamine use is most prevalent in young adults, heart attacks most frequently occur in the elderly population. Thus, Aim 1 of this study is to determine whether sensitization to ischemic injury following either prenatal or early adult exposure to methamphetamine persists into the geriatric phase of life when ischemic heart disease is most common. Aim 2 is to identify the gestational period of vulnerability to this effect of prenatal methamphetamine. Aim 3 is to identify the mechanism by which methamphetamine causes sex-dependent hypersensitivity to ischemic injury. Ischemic heart disease is the leading cause of death in the United States. In light of the prevalence of methamphetamine abuse, it is critical that we understand the impact of prenatal or early adult exposure to methamphetamine on the ischemic heart, including the long term effects that persist in subjects who have stopped using methamphetamine. We anticipate that the proposed work will advance our understanding of the cardiac consequences of prenatal or adult exposure to methamphetamine. These data will also provide insight into methamphetamine induced changes in gene expression that may underlie methamphetamine-induced cardiomyopathy, arrhythmias, and other cardiac pathologies that result from methamphetamine abuse.