THE IMPACT OF POSTTRAUMATIC STRESS DISORDER ON PERIPHERAL VASCULAR FUNCTION

The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. Peripheral vascular dysfunction may be a mechanism by which PTSD increases CVD risk via increases in oxidative stress, inflammation, and/or sympathetic nervous system activity. PURPOSE: This study sought to examine peripheral vascular function in those with PTSD compared to age-matched controls. METHODS: Eight individuals with PTSD (5 women, 3 men; age 22 ± 2 years), and sixteen healthy controls (CON; 10 women, 6 men, 23 ± 2 years), participated in the study. Leg vascular function was assessed via passive leg movement (PLM) technique and evaluated with Doppler ultrasonography. PLM-induced increases in leg blood flow were quantified as peak change in blood flow from baseline (ΔPeak LBF) and blood flow area under the curve (LBF AUC). RESULTS: Significant differences in leg vascular function were revealed between groups. The PTSD group reported significantly lower ΔPeak LBF (PTSD: 294.16 ± 54.16; CON: 594.78 ± 73.70 ml∙min-1; p = 0.01) and LBF AUC (PTSD: 57.23 ± 24.37; CON: 169.92 ± 29.84 ml; p = 0.02) when compared to the CON group. CONCLUSION: This study revealed that lower limb vascular function is impaired in individuals with PTSD when compared to healthy counterparts.https://scholarscompass.vcu.edu/gradposters/1043/thumbnail.jp

Vascular Dysfunction and Posttraumatic Stress Disorder: Examining the Role of Oxidative Stress and Sympathetic Activity

Purpose: The physiological manifestations of posttraumatic stress disorder (PTSD) have been associated with an increase in risk of cardiovascular disease (CVD) independent of negative lifestyle factors. The goal of the study was to better elucidate the mechanisms behind the increased CVD risk by examining peripheral vascular function, a precursor to CVD. Moreover, this study sought to determine the role of oxidative stress and sympathetic nervous system (SNS) activity in PTSD-induced vascular dysfunction. Methods: Sixteen individuals with PTSD (10 women, 6 men; age 24 ± 4 years), and twenty-four healthy controls (CTRL; 15 women, 9 men, 24 ± 4 years), participated in the study. The PTSD group participated in two visits, consuming either a placebo or antioxidant cocktail (AO - vitamins C and E and alpha lipoic acid) prior to their visits, in a randomized order. Arm vascular function was assessed via the reactive hyperemia- induced flow mediated dilation of the brachial artery (BAFMD) technique and evaluated with Doppler ultrasonography. Brachial artery and arm microvascular function were determined by percent change of diameter from baseline normalized for BA shear rate (BAD/Shear), and blood flow area under the curve (BF AUC), respectively. Heart rate variability (HRV) was used to assess autonomic nervous system activity. Results: BF AUC was significantly lower (p = 0.02) and SNS activity was significantly higher (p = 0.02) in the PTSD group when compared to the CTRL group. BAD/Shear was not different between groups. Following the acute AO supplementation, BF AUC was augmented to which it was no longer significantly different (p = 0.16) when compared to the CTRL group. SNS activity within the PTSD group was significantly reduced (p=.007) following the AO supplementation when compared to the PL condition, and the difference between PTSD and CTRL was no longer significant (p=.41). Conclusion: Young individuals with PTSD demonstrated lower arm microvascular, but not brachial artery, function as well as higher sympathetic activity when compared to healthy controls matched for age, sex, and physical activity level. Furthermore, this microvascular dysfunction and SNS activity was attenuated by an acute AO supplementation to the level of the healthy controls. Taken together, this study revealed that the modulation of oxidative stress, via an acute AO supplementation, improved vascular dysfunction in individuals with PTSD, potentially by reducing the substantial SNS activity associated with this disorder.https://scholarscompass.vcu.edu/gradposters/1084/thumbnail.jp

The effect of partial vascular occlusion on oxidative stress and inflammatory markers in young resistance trained individuals

Low-intensity strength training with partial vascular occlusion (PVO)was reported to result in muscle hypertrophy and strength increases similar to high-intensity training without PVO. Resistance training has been reported to increase markers of oxidative stress and inflammation. A recent study reported that PVO by itself may result in elevated oxidative stress markers. The purpose of this study was to examine the effects of PVO on oxidative stress and inflammatory markers. Twelve resistance trained males (18-35yrs) completed three sets of elbow flexion at either moderate (70% 1RM) or low (30% 1RM) intensity with or without PVO. Two rest (R) conditions done with and without PVO were also included. All exercise conditions were done to failure with the exception of one condition done at 30%1RM and repetition matched to the 30%1RM condition with PVO. The seven conditions were completed at least72 hours apart in a counterbalanced fashion over 3-4 weeks. Blood was obtained before and immediately after each condition. Protein carbonyls (PC), glutathione ratio (GSSG/TGSH), xanthine oxidase (XO), oxygen radical absorbance capacity (ORAC), and interleukin-6 (IL-6) were analyzed in the plasma. The addition of PVO impacted the number of repetitions done and time to completion in both the low and moderate intensity conditions. The analysis of PC levels revealed interaction effects which post hoc analysis revealed a time effect for exercise. Glutathione ratio measures revealed a PVO main effect independent of intensity level or time. ORAC analysis revealed significant interaction effects which were intensity x PVO, intensity x time, and PVO x time interactions. XO activity analysis noted an intensity x time interaction resulting from decreases in XO activity over time in both the moderate and low intensity conditions that were not observed in the rest condition. Analysis of IL-6 levels revealed an intensity x time interaction with a significant increase over time for the moderate intensity condition when compared to the rest condition. A PVO x time interaction was also noted and subsequent post-hoc analysis revealed a significant increase over time for the conditions with PVO. This resulted in a greater IL-6 increase over time in conditions with PVO compared to without PVO. The effect of completing each set to failure as opposed to repetitions matched resulted in no differences between low intensity groups without PVO. In summary, this study shows that partial vascular occlusion can increase oxidative stress and inflammation independent of exercise and that combined with low or moderate intensity exercise there was not a significant change in the variables determined using the elbow flexor muscle group

Effects of Dietary Sodium Intake on Blood Flow Regulation During Exercise in Salt Resistant Individuals

PURPOSE: Dietary sodium intake guidelines is ≤2,300 mg/day, yet is exceeded by 90% of Americans. This study examined the impact of a high sodium diet on blood flow regulation during exercise. METHODS: Six males (25 ± 2 years) consumed dietary sodium intake guidelines for two weeks, with one week salt-capsule supplemented (HS: 6,900 mg/day of sodium) and the other week placebo-capsule supplemented (LS: 2,300 mg/day of sodium). At the end of each week, peripheral hemodynamic measurements [blood flow (BF), shear rate (SR), and flow mediated dilation (FMD)/SR)] of the brachial and superficial femoral artery were taken during handgrip (HG) and plantar flexion (PF) exercise, respectively. Each exercise workload was 3 minutes and progressed by 8 kilograms until exhaustion. RESULTS: There were no differences between LS and HS in blood pressure (82 ± 4 v 80 ± 5 mmHg; p = 0.3) or heart rate (56 ± 6 v 59 ± 10 bpm; p = 0.4). HG and PF exercise increased BF, SR, and FMD/SR across workload (p \u3c 0.03 for all), but no difference between diets (p \u3e 0.05 for all). CONCLUSION: Despite previous reports that HS impairs resting vascular function, this study revealed that peripheral vascular function and blood flow regulation during exercise is not impacted by a HS diet.https://scholarscompass.vcu.edu/gradposters/1082/thumbnail.jp

The Effects of a High Fat Meal on Blood Flow Regulation during Arm Exercise

A diet high in saturated fats results in endothelial dysfunction and can lead to atherosclerosis, a precursor to cardiovascular disease. Exercise training is a potent stimulus though to mitigate the negative effects of a high saturated fat diet; however, it is unclear how high-saturated fat meal (HSFM) consumption impacts blood flow regulation during a single exercise session. PURPOSE: This study sought to examine the impact of a single HSFM on peripheral vascular function during an acute upper limb exercise bout. METHODS: Ten young healthy individuals completed two sessions of progressive handgrip exercise. Subjects either consumed a HSFM (0.84 g of fat/kg of body weight) 4 hours prior or remained fasted before the exercise bout. Progressive rhythmic handgrip exercise (6kg, 12kg, 18kg) was performed for 3 minutes per stage at rate of 1 Hz. The brachial artery (BA) diameter and blood velocity was obtained using Doppler Ultrasound (GE Logiq e) and BA blood flow was calculated with these values. RESULTS: BA blood flow and flow mediated dilation (normalized for shear rate) during the handgrip exercise significant increased from baseline in all workloads, but no differences were revealed in response to the HSFM consumption. CONCLUSION: Progressive handgrip exercise augmented BA blood flow and flow mediated dilation in both testing days; however, there was no significant differences following the HSFM consumption. This suggests that upper limb blood flow regulation during exercise is unaltered by a high fat meal in young healthy individuals.https://scholarscompass.vcu.edu/gradposters/1060/thumbnail.jp

Altered skeletal muscle mitochondrial phenotype in COPD: disease vs. disuse

Patients with chronic obstructive pulmonary disease (COPD) exhibit an altered skeletal muscle mitochondrial phenotype, which often includes reduced mitochondrial density, altered respiratory function, and elevated oxidative stress. As this phenotype may be explained by the sedentary lifestyle that commonly accompanies this disease, the aim of this study was to determine whether such alterations are still evident when patients with COPD are compared to control subjects matched for objectively measured physical activity (PA; accelerometry). Indexes of mitochondrial density [citrate synthase (CS) activity], respiratory function (respirometry in permeabilized fibers), and muscle oxidative stress [4-hydroxynonenal (4-HNE) content] were assessed in muscle fibers biopsied from the vastus lateralis of nine patients with COPD and nine PA-matched control subjects (CON). Despite performing similar levels of PA (CON: 18 ± 3, COPD: 20 ± 7 daily minutes moderate-to-vigorous PA; CON: 4,596 ± 683, COPD: 4,219 ± 763 steps per day, P \u3e 0.70), patients with COPD still exhibited several alterations in their mitochondrial phenotype, including attenuated skeletal muscle mitochondrial density (CS activity; CON 70.6 ± 3.8, COPD 52.7 ± 6.5 U/mg, P \u3c 0.05), altered mitochondrial respiration [e.g., ratio of complex I-driven state 3 to complex II-driven state 3 (CI/CII); CON: 1.20 ± 0.11, COPD: 0.90 ± 0.05, P \u3c 0.05), and oxidative stress (4-HNE; CON: 1.35 ± 0.19, COPD: 2.26 ± 0.25 relative to β-actin, P \u3c 0.05). Furthermore, CS activity (r = 0.55), CI/CII (r = 0.60), and 4-HNE (r = 0.49) were all correlated with pulmonary function, assessed as forced expiratory volume in 1 s (P \u3c 0.05), but not PA (P \u3e 0.05). In conclusion, the altered mitochondrial phenotype in COPD is present even in the absence of differing levels of PA and appears to be related to the disease itself

Quadriceps exercise intolerance in patients with chronic obstructive pulmonary disease: the potential role of altered skeletal muscle mitochondrial respiration

This study sought to determine if qualitative alterations in skeletal muscle mitochondrial respiration, associated with decreased mitochondrial efficiency, contribute to exercise intolerance in patients with chronic obstructive pulmonary disease (COPD). Using permeabilized muscle fibers from the vastus lateralis of 13 patients with COPD and 12 healthy controls, complex I (CI) and complex II (CII)-driven State 3 mitochondrial respiration were measured separately (State 3:CI and State 3:CII) and in combination (State 3:CI+CII). State 2 respiration was also measured. Exercise tolerance was assessed by knee extensor exercise (KE) time to fatigue. Per milligram of muscle, State 3:CI+CII and State 3:CI were reduced in COPD (P \u3c 0.05), while State 3:CII and State 2 were not different between groups. To determine if this altered pattern of respiration represented qualitative changes in mitochondrial function, respiration states were examined as percentages of peak respiration (State 3:CI+CII), which revealed altered contributions from State 3:CI (Con 83.7 ± 3.4, COPD 72.1 ± 2.4%Peak, P \u3c 0.05) and State 3:CII (Con 64.9 ± 3.2, COPD 79.5 ± 3.0%Peak, P \u3c 0.05) respiration, but not State 2 respiration in COPD. Importantly, a diminished contribution of CI-driven respiration relative to the metabolically less-efficient CII-driven respiration (CI/CII) was also observed in COPD (Con 1.28 ± 0.09, COPD 0.81 ± 0.05, P \u3c 0.05), which was related to exercise tolerance of the patients (r = 0.64, P \u3c 0.05). Overall, this study indicates that COPD is associated with qualitative alterations in skeletal muscle mitochondria that affect the contribution of CI and CII-driven respiration, which potentially contributes to the exercise intolerance associated with this disease

The Comparison of High-Intensity Interval Exercise vs. Continuous Moderate-Intensity Exercise on C1q/TNF-Related Protein-9 Expression and Flow-Mediated Vasodilation in Obese Individuals

PURPOSE: A recent novel adipocytokine, C1q/TNF-related protein-9 (CTRP9), has been shown to increase activation of endothelial nitric oxide synthase and reduce vasoconstrictors (e.g., endothelin-1). In addition, CTRP9 may play a compensatory role in obesity-related endothelial dysfunction. Although there is limited information regarding exercise-mediated CTRP9, high-intensity interval exercise (HIIE) has been shown to be as or more effective than continuous moderate-intensity exercise (CME) in improving indicators of endothelial function (e.g., brachial artery flow-mediated dilation [BAFMD]). Therefore, the purpose of this study was to investigate the effect of acute HIIE vs. CME on serum CTRP9 and BAFMD responses in obese individuals. METHODS: Sixteen young male subjects (9 obese and 7 normal-weight) participated in a counterbalanced and caloric equated experiment: HIIE (30 minutes, 4 intervals of 4 minutes at 80-90% of VO2max with 3 minutes rest between intervals) and CME (38 minutes at 50-60% VO2max). Serum CTRP9 and BAFMD, were measured prior to, immediately following exercise, and 1 hour and 2 hours into recovery. RESULTS: The concentration of serum CTRP9 was significantly increased immediately following acute HIIE and CME in both obese and normal-weight groups (p = 0.003). Furthermore, both significant treatment by time and group by time interactions for BAFMD were observed following both exercise protocols (p = 0.018; p = 0.009; respectively), with a greater CME-induced BAFMD response at 2 hours into recovery in obese compared to normal-weight subjects. Additionally, a positive correlation in percent change (baseline to peak value) between CTRP9 and BAFMD was found following acute CME (r = 0.589, p = 0.016). CONCLUSIONS: Acute HIIE is as effective as CME to upregulate CTRP9 expression in both obese and normal-weight individuals, although CTRP9 may potentially improve CME-mediated BAFMD. The novel results from this study provide a foundation for additional examination of the mechanisms of exercise-mediated CTRP9 on endothelial function

IFITM3 Inhibits Influenza A Virus Infection by Preventing Cytosolic Entry

To replicate, viruses must gain access to the host cell's resources. Interferon (IFN) regulates the actions of a large complement of interferon effector genes (IEGs) that prevent viral replication. The interferon inducible transmembrane protein family members, IFITM1, 2 and 3, are IEGs required for inhibition of influenza A virus, dengue virus, and West Nile virus replication in vitro. Here we report that IFN prevents emergence of viral genomes from the endosomal pathway, and that IFITM3 is both necessary and sufficient for this function. Notably, viral pseudoparticles were inhibited from transferring their contents into the host cell cytosol by IFN, and IFITM3 was required and sufficient for this action. We further demonstrate that IFN expands Rab7 and LAMP1-containing structures, and that IFITM3 overexpression is sufficient for this phenotype. Moreover, IFITM3 partially resides in late endosomal and lysosomal structures, placing it in the path of invading viruses. Collectively our data are consistent with the prediction that viruses that fuse in the late endosomes or lysosomes are vulnerable to IFITM3's actions, while viruses that enter at the cell surface or in the early endosomes may avoid inhibition. Multiple viruses enter host cells through the late endocytic pathway, and many of these invaders are attenuated by IFN. Therefore these findings are likely to have significance for the intrinsic immune system's neutralization of a diverse array of threats

Stable Isotope Biogeochemistry of Seabird Guano Fertilization: Results from Growth Chamber Studies with Maize (Zea Mays)

Stable isotope analysis is being utilized with increasing regularity to examine a wide range of issues (diet, habitat use, migration) in ecology, geology, archaeology, and related disciplines. A crucial component to these studies is a thorough understanding of the range and causes of baseline isotopic variation, which is relatively poorly understood for nitrogen (δ(15)N). Animal excrement is known to impact plant δ(15)N values, but the effects of seabird guano have not been systematically studied from an agricultural or horticultural standpoint.This paper presents isotopic (δ(13)C and δ(15)N) and vital data for maize (Zea mays) fertilized with Peruvian seabird guano under controlled conditions. The level of (15)N enrichment in fertilized plants is very large, with δ(15)N values ranging between 25.5 and 44.7‰ depending on the tissue and amount of fertilizer applied; comparatively, control plant δ(15)N values ranged between -0.3 and 5.7‰. Intraplant and temporal variability in δ(15)N values were large, particularly for the guano-fertilized plants, which can be attributed to changes in the availability of guano-derived N over time, and the reliance of stored vs. absorbed N. Plant δ(13)C values were not significantly impacted by guano fertilization. High concentrations of seabird guano inhibited maize germination and maize growth. Moreover, high levels of seabird guano greatly impacted the N metabolism of the plants, resulting in significantly higher tissue N content, particularly in the stalk.The results presented in this study demonstrate the very large impact of seabird guano on maize δ(15)N values. The use of seabird guano as a fertilizer can thus be traced using stable isotope analysis in food chemistry applications (certification of organic inputs). Furthermore, the fertilization of maize with seabird guano creates an isotopic signature very similar to a high-trophic level marine resource, which must be considered when interpreting isotopic data from archaeological material