Maternal methamphetamine administration during pregnancy influences on fetal rat heart development

Inoue, Hiromasa; Nakatome, Masato; Terada, Masaru; Mizuno, Minoru; Ono, Ryosuke; Iino, Morio; Ino, Yukiko; Ogura, Yuta; Kuroki, Hidenori; Matoba, Ryoji

doi:10.1016/j.lfs.2003.08.016

Cited by 15 publications

(15 citation statements)

References 34 publications

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“…Inoue et al (21) reported an increased number of mRNA transcripts encoding ␣-myosin heavy chain and disarrangement of myofibers in newborn rat pups, but these effects were reversed by postnatal days 9 and 14, respectively. We are unaware of any other animal studies investigating the effects of prenatal methamphetamine on the adult heart.…”

Section: Discussionmentioning

confidence: 99%

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

Rorabaugh

Seeley

Bui

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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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...

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Section: Discussionmentioning

confidence: 99%

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

Rorabaugh

Seeley

Bui

et al. 2016

American Journal of Physiology-Heart and Circulatory Physiology

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“…72 In animal studies, MA administration to pregnant rats changes alpha-and beta-major histocompatibility complex mRNA expression pattern in fetal and neonatal hearts, resulting in abnormal cardiac development and myocardial damage. 73 There is no human evidence of amphetamine-associated cardiotoxicity and this deserves further study, considering the severe implications of in-utero myocardial damage. Amphetamine-exposed infants, however, are often noted to have smaller head circumferences, even when compared with other drug-exposed newborn infants, 74 and this may be the result of fetal serotonin depletion, leading to reduced total dendritic length and altered dentate granule cell morphology, especially at the synaptic level.…”

Section: Fetal Effectsmentioning

confidence: 99%

Amphetamines, the pregnant woman and her children: a review

et al. 2012

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The objective of this study is to review and summarize available evidence regarding the impact of amphetamines on pregnancy, the newborn infant and the child. Amphetamines are neurostimulants and neurotoxins that are some of the most widely abused illicit drugs in the world. Users are at high risk of psychiatric co-morbidities, and evidence suggests that perinatal amphetamine exposure is associated with poor pregnancy outcomes, but data is confounded by other adverse factors associated with drugdependency. Data sources are Government data, published articles, conference abstracts and book chapters. The global incidence of perinatal amphetamine exposure is most likely severely underestimated but acknowledged to be increasing rapidly, whereas exposure to other drugs, for example, heroin, is decreasing. Mothers known to be using amphetamines are at high risk of psychiatric co-morbidity and poorer obstetric outcomes, but their infants may escape detection, because the signs of withdrawal are usually less pronounced than opiate-exposed infants. There is little evidence of amphetamine-induced neurotoxicity and long-term neurodevelopmental impact, as data is scarce and difficult to extricate from the influence of other factors associated with children living in households where one or more parent uses drugs in terms of poverty and neglect. Perinatal amphetamine-exposure is an increasing worldwide concern, but robust research, especially for childhood outcomes, remains scarce. We suggest that exposed children may be at risk of ongoing developmental and behavioral impediment, and recommend that efforts be made to improve early detection of perinatal exposure and to increase provision of earlyintervention services for affected children and their families.

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“…Demonstrating alcoholic cardiomyopathy by biopsy in a human experimental population, a Barcelona group [2,3] was also able to demonstrate a correspondence between skeletal myopathy and cardiomyopathy. There is a substantial animal literature [4–7] as well as strongly suggestive human case reports [8,9,10,11] and a postmortem survey (12) relating to cardiotoxicity from methamphetamine. However, at present there is neither causal demonstration nor prevalence statistics available in humans for the connection.…”

Section: Introductionmentioning

confidence: 99%

Electrocardiographic abnormalities in methamphetamine abusers

Haning

Goebert

2007

Addiction

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Aims Although many adverse cardiovascular outcomes are mentioned in conjunction with methamphetamine use, a causal relationship between methamphetamine use and arrhythmia or cardiomyopathy has not been demonstrated in man. Clinical experience with methamphetamine users suggested a higher incidence of electrocardiographic abnormalities. This study seeks to quantify that incidence, among subjects enrolled in a study of adults with methamphetamine dependence. Methods Electrocardiograms obtained during screening in a previous clinical trial were examined. The study population (n = 158) of adults with methamphetamine dependence [Diagnostic and Statistical Manual version IV (DSM IV-TR)] was drawn from five sites across the United States, recruited in the interval 2002-03. Results A significant variance from the normal population was noted in the electrocardiograms of the study cohort. Among the abnormalities was a prolongation of the QTc beyond 440 ms in 27.2% of the group. QTc prolongation to this extent poses a particular risk for ventricular arrhythmias, most notably torsades de pointes. Conclusions We believe that this is the first demonstration of clinically significant QTc prolongation in a methamphetamine-using population, and that this has implications for the types of arrhythmias for which this population is at risk. It may further provide a marker for risk of cardiomyopathy. The fact of electrocardiographic changes with potential cardiac risks may be useful in a motivational interviewing approach, in challenging the methamphetamine user's basis for continuing use.

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Maternal methamphetamine administration during pregnancy influences on fetal rat heart development

Cited by 15 publications

References 34 publications

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

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

Amphetamines, the pregnant woman and her children: a review

Electrocardiographic abnormalities in methamphetamine abusers

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