Baroreflex Dysfunction and Augmented Sympathetic Nerve Responses during Combat‐Related and Noncombat‐Related Mental Stress in Veterans with Post‐traumatic Stress Disorder

Patients with post‐traumatic stress disorder (PTSD) are at significantly higher risk of developing hypertension and cardiovascular disease. Mechanisms underlying this increased cardiovascular risk are unclear. Although sympathetic nervous system (SNS) overactivity is presumed to play a role, no prior studies have rigorously examined SNS activity and reactivity in this population, or the underlying control mechanisms regulating sympathetic output, such as the arterial baroreflex. Therefore, we conducted a study testing the hypothesis that PTSD patients have augmented SNS and hemodynamic reactivity during mental stress, and that these augmented responses are due to impaired arterial baroreflex sensitivity (BRS). 13 young, healthy Veterans with combat‐related PTSD were compared to 9 age‐matched Control Veterans without PTSD. All Veterans were deployed during Operation Enduring Freedom (OEF) or Operation Iraqi Freedom (OIF). The Clinician Administered PTSD Scale (CAPS) was used to confirm PTSD diagnosis in patients, and absence of PTSD in Controls. Muscle sympathetic nerve activity (MSNA), beat‐to‐beat arterial blood pressure (BP), and electrocardiography were measured at baseline, and during two types of mental stress: combat‐related stress using virtual reality combat exposure (VRCE) in which first‐person wartime imagery with auditory input was projected using head‐mounted goggles with headphones for 7 minutes; or noncombat related stress using mental arithmetic (MA) for 3 minutes. Cold pressor test (CPT) was also administered for one minute for comparison. BRS was tested at rest using the modified oxford technique in which an intravenous bolus of nitroprusside was administered, followed by a bolus of phenylephrine. BRS was tested again during the last 4 minutes of VRCE in a subset of PTSD (n=6) and Controls (n=4). BRS was assessed as the slope of the linear regression in change in MSNA total activity (TA) and burst incidence (BI, bursts/100 heart beats) against change in diastolic BP. Baseline characteristics, MSNA and hemodynamics were similar between the groups. In PTSD versus Controls, MSNA reactivity (+10.0±1.1 vs +1.2±1.1 bursts/min p=0.001) and heart rate (HR) response (+2.8±0.9 vs −0.7±0.3 beats/min, p=0.009) were significantly augmented during VRCE. Similarly, in PTSD versus Controls, MSNA reactivity (+20.8±2.8 vs +5.9±1.9 bursts/min, p=0.009) and SBP response (+5.9±1.4 vs +0.8±1.7 mmHg, p=0.015) were significantly augmented during MA, but not during CPT (p=NS). In PTSD, BRS assessed using both TA (−1945±342 vs −4030±736 AU/mmHg, p=0.040) and BI (−1.07±0.25 vs −2.05±0.36 BI/mmHg) were significantly blunted at rest, and there was a trend towards blunted BRS assessed using BI during VRCE (−0.99±0.20 vs −3.12±0.75, p=0.095). These data demonstrate that PTSD patients have augmented SNS and HR responses during combat‐related mental stress. Heightened SNS responses in PTSD extend to other forms of mental stress such as MA, but not to all sympathoexcitatory stimuli such as CPT. BRS was significantly blunted at rest and there was a trend towards blunted BRS during VRCE in PTSD, suggesting that blunted BRS may contribute to SNS overactivation during mental stress in PTSD. Exaggerated BP and SNS responses during mental stress, and impaired BRS may contribute to increased risk of hypertension and cardiovascular disease in young PTSD patients. Support or Funding Information Supported by VA Merit Grant 1I01CX001065; American Heart Association 15CSA24340001