Impact of an Animal Model of Posttraumatic Stress Disorder on the Ischemic Heart - Abstract
Individuals who are exposed to life-threatening trauma are at significant risk of developing post-traumatic
stress disorder (PTSD). People with PTSD experience extreme psychological distress by repeatedly reliving
their trauma through intrusive flashback memories. These memories are accompanied by other symptoms,
including emotional numbing, avoidance of stimuli associated with the trauma, and a persistent state of
hypervigilance. In addition to the psychological manifestations, PTSD is also associated with enhanced
progression of coronary atherosclerosis and an increased likelihood of experiencing a myocardial infarction.
However, the impact of PTSD on the ischemic heart has not been well studied. Specifically, it is unclear
whether PTSD induces myocardial changes that influence the extent of ischemia-induced injury. Such studies
are difficult to conduct in human patients because PTSD is associated with increased rates of smoking,
sedentary lifestyle, diabetes, depression, and other factors that influence cardiovascular function. Thus, our
laboratory is using an animal model of PTSD to examine its impact on the myocardial response to ischemic
injury. The model is advantageous because it permits the controlled induction of myocardial ischemia
independent of atherosclerotic blockage of coronary arteries, and it avoids the confounding cardiovascular risk
factors mentioned above. Our preliminary studies provide evidence that this animal model of PTSD induces
changes in the heart that increase myocardial sensitivity to ischemic injury. Some of the physiological and
behavioral alterations induced by this model can be reversed or prevented by drugs that are used to treat
human PTSD patients. However, it is unknown whether these agents can reverse the increased myocardial
sensitivity to ischemic injury that results from this exposure to this model. Therefore, Aim 1 of this study is to
determine whether the psychosocial stress-induced increase in myocardial sensitivity to ischemic injury can be
reversed or prevented by pharmacotherapy. Exposure to this rat model of PTSD increases cerebral and
hippocampal production of pro-inflammatory cytokines, increases signaling through the pro-inflammatory NF-
κB signaling pathway, and increases the production of reactive oxygen species. Inflammation and oxidative
stress are important components of myocardial ischemic injury. However, it is unknown whether the pro-
inflammatory events that have been reported in the brain following exposure to this PTSD model also occur in
the heart. Aim 2 of this study is to identify the mechanism by which this PTSD model increases myocardial
sensitivity to ischemic injury. Finally, women are at significantly greater risk of developing PTSD than men.
However, few animal models of PTSD have included females because of complexities associated with the
effects of the estrous cycle on the stress response. Aim 3 of this study is to examine the influence of estrous
stage on behavioral responses and myocardial sensitivity to ischemic injury in female rats exposed to our
animal model of PTSD.
