Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts

Abstract

Rorabaugh BR, Seeley SL, Bui AD, Sprague L, D'Souza MS. Prenatal methamphetamine differentially alters myocardial sensitivity to ischemic injury in male and female adult hearts. Am J Physiol Heart Circ Physiol 310: H516 -H523, 2016. First published December 18, 2015 doi:10.1152/ajpheart.00642.2015-Methamphetamine is one of the most common illicit drugs abused during pregnancy. The neurological effects of prenatal methamphetamine are well known. However, few studies have investigated the potential effects of prenatal methamphetamine on adult cardiovascular function. Previous work demonstrated that prenatal cocaine exposure increases sensitivity of the adult heart to ischemic injury. Methamphetamine and cocaine have different mechanisms of action, but both drugs exert their effects by increasing dopaminergic and adrenergic receptor stimulation. Thus the goal of this study was to determine whether prenatal methamphetamine also worsens ischemic injury in the adult heart. Pregnant rats were injected with methamphetamine (5 mg·kg Ϫ1 ·day Ϫ1 ) or saline throughout pregnancy. When pups reached 8 wk of age, their hearts were subjected to ischemia and reperfusion by means of a Langendorff isolated heart system. Prenatal methamphetamine had no significant effect on infarct size, preischemic contractile function, or postischemic recovery of contractile function in male hearts. However, methamphetamine-treated female hearts exhibited significantly larger infarcts and significantly elevated enddiastolic pressure during recovery from ischemia. Methamphetamine significantly reduced protein kinase Cε expression and Akt phosphorylation in female hearts but had no effect on these cardioprotective proteins in male hearts. These data indicate that prenatal methamphetamine differentially affects male and female sensitivity to myocardial ischemic injury and alters cardioprotective signaling proteins in the adult heart. prenatal methamphetamine; ischemia; heart; pregnancy; drug abuse NEW & NOTEWORTHY Prenatal exposure to methamphetamine increases myocardial sensitivity to ischemic injury and alters proteins involved in cardioprotective signaling pathways in the adult female rat heart. These changes were not observed in male hearts. The responses of adult male and female hearts to an ischemic insult are differentially altered by prenatal methamphetamine.METHAMPHETAMINE is one of the most common illicit drugs abused during pregnancy (2, 29). One study found that 5.2% of pregnant women use methamphetamine at some point during their pregnancy (2). Most studies of prenatal methamphetamine have focused on the impact of this drug on behavior and cognitive effects during early childhood. Prenatal methamphetamine produces a variety of neurological effects, including structural changes in the brain (8, 37), increased prevalence of cognitive and behavioral problems (11, 23), delayed development of gross motor skills (42), and decreased verbal and spatial memory (8). In contrast to these neurological effects, the impact of prenatal methamphetamin...

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

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Methamphetamine Consumption during Pregnancy – Effects on Child Health

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“…Recent animal studies suggest an effect on the cardiovascular function of PME in adulthood. Female offspring of methamphetamine-treated pregnant rats exhibited significantly larger infarcts in a cardiac ischemia-reperfusion model at an age of 8 weeks [33].…”

Drogenabusus in der Schwangerschaft – Risiko für das Kind

“…Anzustreben ist, die Kinder und Mütter in einem staatlichen Register zu erfassen, wie in Tschechien und Schweden seit Jahren eingeführt [18] [19,20]. Methamphetamine weisen auch einen negativen Effekt auf die adulte myokardiale Funktion auf [21]. In eigenen Studien konnten wir bei etwa 25 % der untersuchten Kinder postnatal eine Einschränkung der kardialen Adaptationsfähigkeit feststellen.…”