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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 InformationThis 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.

Background: Concurrent administration of vancomycin and piperacillin/tazobactam (VAN+PTZ) may increase the risk of acute kidney injury (AKI) in hospitalized patients. Comprehensive characterization of VAN+PTZ associated AKI and recovery patterns remains lacking in previous reports. Objective: To compare the incidence of AKI associated with VAN+PTZ compared to either cefepime (CEF) or meropenem (MER) with VAN in adult general ward patients. Methods: A multicenter, retrospective, propensity score cohort study was conducted in non-critically ill adult patients. Included patients were concurrently administered VAN+PTZ or VAN+CEF/MER. Patients developing AKI ≤48 hours following combination therapy were excluded. The primary endpoint was to compare the incidence of AKI between study groups. Multivariable Cox regression modeling in predicting AKI was also conducted. Results: A total of 3199 patients met inclusion criteria and were evaluated. The incidence of AKI in VAN+PTZ and VAN+CEF/MER groups were 16.4% and 8.7%, respectively ( P < .001). The onset to AKI was 1.8 days earlier with VAN+PTZ compared to VAN+CEF/MER ( P < .001). Multivariable prediction model showed concomitant VAN+PTZ was identified as an independent risk factor of developing AKI (HR 2.34, 1.82-3.01, P < .001). The VAN+PTZ group experienced significantly higher rates of severe AKI (stage II or III) compared to the VAN+CEF/MER group ( P = .002). No differences in the AKI recovery patterns were found between study groups. Conclusions: Concomitant VAN+PTZ in adult general ward patients was independently associated with an increased risk of AKI overall. More severe AKI was also associated with VAN+PTZ.