Myocardial Hypersensitivity to Ischemic Injury is not Blocked by Clonidine or Propranolol in a Predator-Based Model of PTSD

Individuals with posttraumatic stress disorder (PTSD) are at increased risk for cardiovascular disease. We previously reported that a predator‐based psychosocial stress model of PTSD led to myocardial hypersensitivity to ischemic injury. Heightened sympathetic signaling has a well‐established role in the formation of anxiety and fear‐related memories associated with PTSD. In addition, chronic β‐adrenergic signaling is known to increase myocardial sensitivity to ischemia. Thus, we examined whether suppression of sympathetic signaling would protect the ischemic heart in rats subjected to the psychosocial stress model of PTSD. Male Sprague‐Dawley rats were exposed to psychosocial stress or control conditions for 31 days. Stressed rats were given two cat exposures (separated by 10 days) and subjected to daily social instability throughout the 31 day paradigm. Control rats were handled daily but were not exposed to the cat or to social instability. In the first set of experiments, rats received daily intraperitoneal injections of either clonidine (0.05 mg/kg) or saline beginning on day 2 and continuing through day 31. Rats were tested for anxiety‐like behavior on the elevated plus maze (EPM) on Day 32. Hearts were isolated on day 33 and subjected to 20 minutes ischemia and 2 hours reperfusion on a Langendorff isolated heart system. Stressed rats exhibited increased anxiety‐like behavior on the EPM, as well as significantly larger myocardial infarcts following ischemia. Clonidine reversed the anxiety‐like behavior on the EPM, but had no effect on infarct size. In a second set of experiments, half of the rats were given propranolol (0.5 g/l) in their drinking water starting on day 2 and continuing throughout the 31 day psychosocial stress paradigm. Propranolol had no effect on either anxiety‐like behavior or infarct size. These findings suggest that the increased myocardial sensitivity to ischemic injury observed in this rat model of PTSD is not caused by increased sympathetic tone or by chronic β‐adrenergic receptor signaling. Support or Funding Information This work was supported by R15HL132322 to B.R.R. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .