Abstract 105: Increased Myocardial Sensitivity to Ischemic Injury in an Animal Model of Posttraumatic Stress Disorder

Background: Posttraumatic stress disorder (PTSD) is a psychological disorder characterized by the formation of traumatic memories following exposure to a life threatening event. In addition to psychological manifestations, PTSD promotes atherosclerosis and increases the incidence of myocardial infarction. However, it is unknown whether the effects of PTSD are limited to increasing the incidence of myocardial infarction or if PTSD also increases infarct severity. Therefore, we used an animal model of PTSD to determine whether posttraumatic stress influences infarct size and postischemic recovery of cardiac contractile function. Methods: Rats were subjected to a well-established animal model of PTSD that is based on predator exposure and psychosocial stress (Zoladz et al., Stress 11:259-281). Rats subjected to this model exhibit many PTSD-like characteristics including the formation of traumatic memories, increased anxiety, increased startle reflex, hypertension, and alterations in the hypothalamic-pituitary adrenal axis. Male rats (7 weeks of age) were either subjected to psychosocial stress (n = 9) or continuously housed in their home cages (n = 8) for 31 days. Hearts were subsequently isolated and subjected to 20 minutes of ischemia and 2 hours reperfusion on a Langendorff isolated heart system. Results: Stressed rats exhibited significantly elevated corticosterone concentrations and anxiety-like behavior in the elevated plus maze. Infarct sizes were significantly larger in hearts from stressed rats (44.7 ± 1.7 % of area at risk) compared to nonstressed rats (31.0 ± 5.4 % of area at risk). Consistent with increased myocardial injury, postischemic recovery of rate pressure product (stressed = 16,922 ± 1,554 mmHg*bpm; nonstressed = 26,407 ± 2,977 mmHg*bpm) and +dP/dT (stressed = 1,901 ± 189 mmHg/sec; nonstressed =3,259 ± 498 mmHg/sec) were significantly attenuated in hearts from stressed rats. Furthermore, postischemic end diastolic pressure was significantly elevated in hearts from stressed (57 ± 6 mmHg) compared to nonstressed (32 ± 7 mmHg) rats. Conclusion: This animal model suggests that PTSD may make the myocardium more sensitive to ischemic injury through a mechanism that is independent from its ability to promote atherosclerosis.