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

产前或成人接触甲基苯丙胺对缺血性心脏的影响

• 批准号: 10001712
• 负责人: Boyd Rorabaugh
• 金额: $ 42.91万
• 依托单位: MARSHALL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001712
• 关键词: Abstinence; Acute; Adult; Age; Age-Months; Age-Years; Animals; Arrhythmia; Cardiac; Cardiac Myocytes; Cardiomyopathies; Cardiovascular system; Cause of Death; Child; Data; Drug usage; Drug user; Elderly; Estrogens; Exposure to; Female; Female of child bearing age; Gene Expression; Heart; Hypersensitivity; Illicit Drugs; Injury; Ischemia; Learning; Life; Light; Long-Term Effects; Mediating; Methamphetamine; Myocardial; Myocardial Infarction; Myocardial Ischemia; Neurological outcome; Pathology; Pharmaceutical Preparations; Phase; Population; Pregnancy; Prevalence; Rattus; Recording of previous events; Relapse; Reporting; Research; Risk; Same-sex; Siblings; Time; United States; Woman; Work; age group; aged; cardioprotection; drug abstinence; emerging adult; illicit drug use; insight; male; methamphetamine abuse; methamphetamine effect; methamphetamine exposure; methamphetamine use; methamphetamine user; offspring; pregnant; prenatal; prenatal exposure; response; sex; virtual; young adult

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.

摘要 甲基苯丙胺是美国最常滥用的非法药物之一。甲基苯丙胺 吸毒在18 - 34岁的成年人中最为普遍。值得注意的是，这一年龄组的妇女 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系统方面， 结果。相反，产前接触甲基苯丙胺对成人心血管系统的影响 系统几乎被忽略了。此外，大多数研究甲基苯丙胺对 心脏的研究集中在目前或最近使用该药物的受试者的急性效应上。很少有研究 已经研究了甲基苯丙胺对人或动物心血管的长期影响， 甲基苯丙胺接触史（产前或成年期），但不再使用 冰毒最近的研究表明，在产前接触甲基苯丙胺 或在成年早期引起缺血性心脏的性别依赖性变化。雌性大鼠，但不是它们的 在产前或成年早期暴露于甲基苯丙胺的男性兄弟姐妹， 对缺血性损伤超敏反应。此外，对缺血的超敏反应在一段时间后仍然存在。 戒断药物，表明甲基苯丙胺可能会引起心脏的性依赖性变化 是不可逆转的这些数据表明，患有心脏病的女性可能面临更多的风险。 广泛的心肌损伤，如果他们暴露于甲基苯丙胺在产前期间，或 在成年早期，即使他们已经保持了很长一段时间的禁欲， 时间虽然甲基苯丙胺的使用在年轻人中最普遍，但心脏病发作最常发生在年轻人中。 老年人口。因此，本研究的目的1是确定是否致敏缺血损伤， 在出生前或成年早期接触甲基苯丙胺后， 缺血性心脏病最常见的时候目的2是确定妊娠期易受 产前甲基苯丙胺的影响目的3是确定甲基苯丙胺 导致对缺血性损伤的性别依赖性超敏反应。缺血性心脏病是导致死亡的主要原因 在美国鉴于甲基苯丙胺滥用的普遍性，我们必须了解 产前或成年早期接触甲基苯丙胺对缺血性心脏的影响，包括长期 在停止使用甲基苯丙胺的受试者中持续存在的影响。我们预计， 这项工作将促进我们对产前或成人暴露于 冰毒这些数据也将提供深入了解甲基苯丙胺诱导的基因变化， 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症。