Impact of methamphetamine on the ischemic hearts of three generations of rats
Approximately 5 % of the United States population has used methamphetamine at some point in their lifetime. Methamphetamine is known to increase the risk of a myocardial infarction, but it is unclear whether methamphetamine alters the extent of myocardial injury. The first goal of this study was to determine whether repeated methamphetamine exposure alters the extent of injury in the ischemic heart. Adult rats received daily subcutaneous injections of methamphetamine (5 mg/kg) or saline for 10 days, and their hearts were subjected to an ischemic insult on day 11 using a Langendorff isolated heart apparatus. Hearts from methamphetamine-treated female rats exhibited significantly larger infarcts and significantly suppressed postischemic recovery of contractile function compared to hearts from saline-treated females. In contrast, infarct size and postischemic recovery of contractile function were unaffected by methamphetamine in males. The second goal was to determine whether prenatal methamphetamine exposure alters myocardial sensitivity to ischemic injury during adulthood. Pregnant rats (F0 generation) received daily injections of methamphetamine (5 mg/kg) or saline throughout the duration of their pregnancy. When the F1 pups reached 8 weeks of age, their hearts were subjected to an ischemic insult. Infarcts were significantly larger in adult female hearts that had been prenatally exposed to methamphetamine compared to control females that were prenatally exposed to saline. In addition, protein kinase C-ɛ expression and Akt phosphorylation were decreased in hearts from methamphetamine-exposed females. In contrast, methamphetamine had no impact on infarct size, PKC-ɛ, or Akt phosphorylation in their male littermates. Others have reported that rat pups (F2) born to parents (F1) that were prenatally exposed to methamphetamine exhibit deficits in sensory-motor coordination. Thus, F1 rats that had been prenatally exposed to methamphetamine were used as breeders to produce the F2 generation of rats. Hearts from F2 rats were subjected to an ischemic insult when they reached 8 weeks of age. We found no evidence for myocardial hypersensitivity to ischemic injury in the F2 generation that was not directly exposed to methamphetamine. These data provide evidence that a history of adult or prenatal exposure to methamphetamine worsens ischemic injury in the adult heart. This could have significant implications for people who have both ischemic heart disease and a history of adult or prenatal exposure to methamphetamine.
Rorabaugh BR, Seeley SL, Stoops T, Sprague L, Bui A, D’Souza MS. Impact of methamphetamine on the ischemic hearts of three generations of rats. Experimental Biology meeting, Chicago, IL.