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Context: We previously reported positive behavioral effects of both daily mantra meditation and classical music listening interventions in breast cancer survivors with cancer related cognitive complaints. Objective: The objective of this pilot study was to compare the effects of the meditation intervention to a music listening intervention on biomarkers of inflammation and cellular aging (secondary outcomes) in breast cancer survivors. Design: Randomized control trial, baseline data collection (time 1), post intervention data collection (time 2) Setting: Community-based, Central Texas Participants: 25 breast cancer survivors (BCS) who were 3 months to 6 years post chemotherapy completion and reported cognitive decline Intervention(s): Kirtan Kriya meditation (KK) or music listening (ML), 8 weeks, 12 minutes a day Main Outcome: Telomerase activity [TA], c-reactive protein [CRP], soluble IL-2 receptor alpha [sIL-2Rα], soluble IL-4 receptor [sIL-4R], soluble IL-6 receptor [sIL-6R], soluble tumor necrosis factor receptor II [sTNF-RII], VEGF receptor 2 [sVEGF-R2], and VEGF receptor 3 [sVEGF-R3] Results: Repeated measures analysis of variance models were analyzed from time 1 to time 2 by group for each biomarker. A pattern of greater telomerase activity across time in both groups (F (1,15) = 3.98, p = .06, η²p = .21); significant decreases in sIL-4R across time for both groups (F (1,22)= 6.28, p = .02, η²p = .22); group*time effect was nominally different but not statistically different for sIL-4R (F(1,22)= 3.82, p = .06, η²p = .15); and a pattern for a group*time effect with ML group showing higher levels of sVEGF-R3 at time 2 (F (1,20)=, p = .12, η²p = .11). No significant effects were found for CRP, sIL-2Rα, sIL-6R, sTNF-RII, or sVEGF-R2.

Studies have shown that early-stage type 1 diabetes mellitus (T1DM) leads to an exaggerated reflex pressor response to both static muscle contraction and tendon stretch. However, whether similar responses are present during dynamic exercise (i.e., intermittent contraction) is not known. Therefore, the purpose of this study was to determine whether T1DM leads to an exaggerated reflex pressor response to intermittent muscle contraction. We measured the exercise pressor reflex in unanesthetized, decerebrated T1DM (50 mg/kg streptozotocin; STZ) and healthy control (CTL) Sprague-Dawley rats by intermittently contracting the hindlimb muscles for 30 s while measuring mean arterial pressure (MAP), renal sympathetic nerve activity (RSNA), and heart rate (HR). Intermittently contracting the hindlimb muscles evoked exaggerated mean RSNA (STZ: Δ109 ± 21%

Introduction: Studies in humans and animals have found that type 2 diabetes mellitus (T2DM) exaggerates the blood pressure (BP) response to exercise, which increases the risk of adverse cardiovascular events such as heart attack and stroke. T2DM is a chronic disease that, without appropriate management, progresses in severity as individuals grow older. Thus, it is possible that aging may also exaggerate the BP response to exercise. Therefore, the purpose of the current study was to determine the effect of the pathophysiology of T2DM on the exercise pressor reflex independent of aging.Methods: We compared changes in peak pressor (mean arterial pressure; ΔMAP), BP index (ΔBPi), heart rate (ΔHR), and HR index (ΔHRi) responses to static contraction, intermittent contraction, and tendon stretch in UCD-T2DM rats to those of healthy, age-matched Sprague Dawley rats at three different stages of the disease.Results: We found that the ΔMAP, ΔBPi, ΔHR, and ΔHRi responses to static contraction were significantly higher in T2DM rats (ΔMAP: 29 ± 4 mmHg; ΔBPi: 588 ± 51 mmHg•s; ΔHR: 22 ± 5 bpm; ΔHRi: 478 ± 45 bpm•s) compared to controls (ΔMAP: 10 ± 1 mmHg, p < 0.0001; ΔBPi: 121 ± 19 mmHg•s, p < 0.0001; ΔHR: 5 ± 2 bpm, p = 0.01; ΔHRi: 92 ± 19 bpm•s, p < 0.0001) shortly after diabetes onset. Likewise, the ΔMAP, ΔBPi, and ΔHRi to tendon stretch were significantly higher in T2DM rats (ΔMAP: 33 ± 7 mmHg; ΔBPi: 697 ± 70 mmHg•s; ΔHRi: 496 ± 51 bpm•s) compared to controls (ΔMAP: 12 ± 5 mmHg, p = 0.002; ΔBPi: 186 ± 30 mmHg•s, p < 0.0001; ΔHRi: 144 ± 33 bpm•s, p < 0.0001) shortly after diabetes onset. The ΔBPi and ΔHRi, but not ΔMAP, to intermittent contraction was significantly higher in T2DM rats (ΔBPi: 543 ± 42 mmHg•s; ΔHRi: 453 ± 53 bpm•s) compared to controls (ΔBPi: 140 ± 16 mmHg•s, p < 0.0001; ΔHRi: 108 ± 22 bpm•s, p = 0.0002) shortly after diabetes onset.Discussion: Our findings suggest that the exaggerated exercise pressor reflex and mechanoreflex seen in T2DM are due to the pathophysiology of the disease and not aging.

Context Physical activity for women with early-stage breast cancer is well recognized for managing cancer-related symptoms and improving quality of life. While typically excluded from interventions, women with metastatic breast cancer may also benefit from physical activity. Objective To 1) determine the safety and feasibility of a physical activity program for women with metastatic breast cancer and 2) explore the efficacy of the program. Methods Fourteen women with metastatic breast cancer were randomized to either a control group or an 8-week home-based physical activity intervention comprising twice weekly supervised resistance training and an unsupervized walking program. Results The recruitment rate was 93%. Adherence to the resistance and walking components of the program was 100% and 25%, respectively. No adverse events were reported. When mean change scores from baseline to postintervention were compared, trends in favor of the exercise group over the control group were observed for the Functional Assessment of Chronic Illness Therapy-Fatigue score (+5.6 ± 3.2 vs. −1.8 ± 3.9, respectively), VO2max (+1.6 ml/kg/minute ±1.8 mL/kg/minute vs. −0.2 mL/kg/minute ±0.1 mL/kg/minute, respectively) and six-minute walk test (+40 m ± 23 m vs. −46 m ± 56 m, respectively). Conclusion A partially supervised home-based physical activity program for women with metastatic breast cancer is feasible and safe. The dose of the resistance training component was well tolerated and achievable in this population. In contrast, adherence and compliance to the walking program were poor. Preliminary data suggest a physical activity program, comprising predominantly resistance training, may lead to improvements in physical capacity and may help women to live well with their disease.

The aim of CATS (Cardiotoxicity of Adjuvant Trastuzumab Study) was to prospectively assess clinical, biochemical, and genomic predictors of trastuzumab-related cardiotoxicity (TRC).Cardiac dysfunction is a common adverse effect of trastuzumab. Studies to identify predictive biomarkers for TRC have enrolled heterogeneous populations and yielded mixed results.A total of 222 patients with early-stage human epidermal growth factor receptor 2-positive breast cancer scheduled to receive adjuvant anthracyclines followed by 12 months of trastuzumab were prospectively recruited from 17 centers. Left ventricular ejection fraction (LVEF), troponin T, and N-terminal prohormone of brain natriuretic peptide were measured at baseline, post-anthracycline, and every 3 months during trastuzumab. Germline single-nucleotide polymorphisms in ERBB2, FCGR2A, and FCGR3A were analyzed. TRC was defined as symptomatic heart failure; cardiac death, arrhythmia, or infarction; a decrease in LVEF of15% from baseline; or a decrease in LVEF of10% to 50%.TRC occurred in 18 of 217 subjects (8.3%). Lower pre-anthracycline LVEF and greater interval decline in LVEF from pre- to post-anthracycline were each associated with TRC on multivariate analyses (odds ratio: 3.9 [p = 0.0001] and 7.9 [p 0.0001] for a 5% absolute change in LVEF). Higher post-anthracycline N-terminal prohormone of brain natriuretic peptide level was associated with TRC on univariate but not multivariate analyses. There were no associations between troponin T or ERBB2/FGCR polymorphisms and TRC. Baseline LVEF and LVEF change post-anthracycline were used to generate a "low-risk TRC score" to identify patients with low TRC incidence.Low baseline LVEF and greater LVEF decline post-anthracycline were both independent predictors of TRC. The other biomarkers did not further improve the ability to predict TRC. (Cardiotoxicity of Adjuvant Trastuzumab [CATS]; NCT00858039).

Recent findings have shown that muscle contraction evokes an exaggerated pressor response in type 1 diabetes mellitus (T1DM) rats; however, it is not known whether the mechanoreflex, which is commonly stimulated by stretching the Achilles tendon, contributes to this abnormal response. Furthermore, the role of mechano-gated Piezo channels, found on thin-fiber afferent endings, in evoking the mechanoreflex in T1DM is also unknown. Therefore, in male and female streptozotocin (STZ, 50 mg/kg)-induced T1DM and healthy control (CTL) rats, we examined the pressor and cardioaccelerator responses to tendon stretch during the early stage of the disease. To determine the role of Piezo channels, GsMTx-4, a selective Piezo channel inhibitor, was injected into the arterial supply of the hindlimb. At 1 wk after STZ injection in unanesthetized, decerebrate rats, we stretched the Achilles tendon for 30 s and measured pressor and cardioaccelerator responses. We then compared pressor and cardioaccelerator responses to tendon stretch before and after GsMTx-4 injection (10 µg/100 ml). We found that the pressor (change in mean arterial pressure) response [41 ± 5 mmHg ( n = 15) for STZ and 18 ± 3 mmHg ( n = 11) for CTL ( P < 0.01)] and cardioaccelerator (change in heart rate) response [18 ± 4 beats/min for STZ ( n = 15) and 8 ± 2 beats/min ( n = 11) for CTL ( P < 0.05)] to tendon stretch were exaggerated in STZ rats. Local injection of GsMTx-4 attenuated the pressor [55 ± 7 mmHg ( n = 6) before and 27 ± 9 mmHg ( n = 6) after GsMTx-4 ( P < 0.01)], but not the cardioaccelerator, response to tendon stretch in STZ rats and had no effect on either response in CTL rats. These data suggest that T1DM exaggerates the mechanoreflex response to tendon stretch and that Piezo channels play a role in this exaggeration.

Chronic immune activation and ensuing inflammation that accompany HIV infection lead to adverse metabolic consequences and an increased risk of type 2 diabetes (T2D). We examined the additive effects of T2D on circulating biomarkers involved in inflammation, coagulation, and vascular function along with plasma amino acids in people living with HIV (PLWH). This cross-sectional study included PLWH with and without T2D (n = 32 total). Analyses involved a multiplex platform for circulating biomarkers and gas chromatography-vacuum ultraviolet spectroscopy for plasma amino acids. In PLWH and T2D, both fibrinogen (2.0 ± 0.6 vs 1.6 ± 0.4 µg/mL, p = 0.02) and von Willebrand factor (vWF) (40.8 ± 17.2 vs 26.7 ± 13.8 µg/mL, p = 0.02) were increased and tryptophan (47 ± 6 vs 53 ± 8 nmol/mL, p = 0.03) and threonine (102 ± 25 vs 125 ± 33 nmol/mL, p = 0.03) were decreased. Fibrinogen, as a biomarker of inflammation, and vWF, as a biomarker of endothelial dysfunction, are augmented by the combined effects of HIV and T2D and may contribute to the pathogenesis of T2D in PLWH. Chronic immune activation and inflammation compromise the integrity of the intestinal mucosa, which increases mucus production. Tryptophan metabolism is altered by a loss of intestinal membrane integrity and threonine is consumed in the production of mucus. Metabolic competition arising from increased protein synthesis in the setting of chronic inflammation along with the associated loss in intestinal membrane integrity may be a primary mechanism in the pathogenesis of T2D in PLWH and requires further investigation.

Emerging evidence suggests the exercise pressor reflex is exaggerated in early-stage type 1 diabetes mellitus (T1DM). Piezo channels may play a role in this exaggeration since blocking these channels attenuates the exaggerated pressor response to tendon stretch in T1DM rats. However, tendon stretch constitutes a different mechanical and physiological stimuli than that occurring during muscle contraction. Therefore, the purpose of this study was to determine the contribution of Piezo channels in evoking the pressor reflex during an intermittent muscle contraction in T1DM. In unanaesthetized, decerebrate rats we compared the pressor and cardioaccelerator responses to intermittent muscle contraction before and after locally injecting GsMTx-4 (0.25 µM) into the hindlimb vasculature. Although GsMTx-4 has a high potency for Piezo channels, it has also been suggested to block TRPC channels. We, therefore, performed additional experiments to control for this possibility by also injecting SKF 96365 (10 µM), a TRPC channel blocker. We found that local injection of GsMTx-4, but not SKF 96365, attenuated the exaggerated peak pressor (ΔMAP before: 33±3 mmHg, after: 22±3 mmHg, p=0.007) and pressor index (ΔBPi before: 668±91 mmHg·s, after: 418±81 mmHg·s, p=0.021) response in STZ rats (n=8). GsMTx-4 attenuated the exaggerated early-onset pressor as well as the pressor response over time, which eliminated peak differences as well as those over time between T1DM and healthy controls. These data suggest that Piezo channels are an effective target to normalize the exercise pressor reflex in T1DM.

The exercise pressor reflex is exaggerated in type 2 diabetes mellitus (T2DM). Hyperglycemia, a main characteristic of T2DM, likely contributes to this exaggerated response. However, the isolated effect of acute hyperglycemia, independent of T2DM, on the exercise pressor reflex is not known. Therefore, the purpose of this study was to determine the effect of acute, local exposure to hyperglycemia on the exercise pressor reflex and its two components, namely the mechanoreflex and the metaboreflex, in healthy rats. To accomplish this, we determined the effect of an acute locol intra-arterial glucose infusion (0.25 g/mL) on cardiovascular responses to static contraction (i.e., exercise pressor reflex) and tendon stretch (i.e., mechanoreflex) for 30 s, as well as hindlimb intra-arterial lactic acid (24 mM) injection (i.e., metaboreflex) in fasted unanesthetized, decerebrated Sprague-Dawley rats. We measured and compared changes in mean arterial pressure (MAP) and heart rate (HR) before and after glucose infusion. We found that acute glucose infusion did not affect the pressor response to static contraction (ΔMAP: before: 15 ± 2 mmHg, after: 12 ± 2 mmHg; n = 8, p > 0.05), tendon stretch (ΔMAP: before: 12 ± 1 mmHg, after: 12 ± 3 mmHg; n = 8, p > 0.05), or lactic acid injection (ΔMAP: before: 13 ± 2 mmHg, after: 17 ± 3 mmHg; n = 9, p > 0.05). Likewise, cardioaccelerator responses were unaffected by glucose infusion, p > 0.05 for all. In conclusion, these findings suggest that acute, local exposure to hyperglycemia does not affect the exercise pressor reflex or either of its components.

PURPOSE The effect of menstrual blood loss on oxygen-carrying capacity remains equivocal. The purpose of this study was to determine the effect of menstrual blood loss on hemoglobin mass in young, healthy women. METHODS Twenty-one women (age, 23 ± 6 yr; height, 168 ± 7 cm; weight, 66.1 ± 12.6 kg) with regular menstrual cycles, either using (n = 10) or not using oral contraceptives, participated in the study. Hemoglobin mass was assessed using carbon monoxide rebreathing on three separate occasions over the course of one menstrual cycle. RESULTS Visits for women not using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (1 ± 1 d after the surge of luteinizing hormone in urine), and luteal phase (9 ± 1 d after the late follicular visit). Visits for women using oral contraceptives were performed in the early follicular phase (3 ± 1 d after the onset of menses), late follicular phase (15 ± 3 d after the onset of menses), and luteal phase (9 ± 2 d after the late follicular visit). Hemoglobin mass was not affected by menstrual cycle phase (early follicular, 618 ± 61; late follicular, 610 ± 65; luteal, 607 ± 68 g; P = 0.52). Interestingly, when normalized to weight, hemoglobin mass was 12% higher in women using oral contraceptives in comparison to nonusers (10.0 ± 1.2 vs 8.9 ± 1.2 g·kg, P < 0.05). CONCLUSION Menstrual blood loss had no measurable effect on hemoglobin mass in eumenorrheic women. However, oral contraceptive use resulted in a greater oxygen-carrying capacity, potentially leading to a greater maximal oxygen uptake.

INTRODUCTION: The purpose of this study is to explore 13 cytokine predictors of chemotherapy-related cognitive impairment (CRCI) in breast cancer survivors (BCS) 6 months to 10 years after chemotherapy completion using a multivariate, non-parametric approach. METHODS: Cross sectional data collection included completion of a survey, cognitive testing, and non-fasting blood from 66 participants. Data were analyzed using random forest regression to identify the most significant predictors for each of the cognitive test scores. RESULTS: A different cytokine profile predicted each cognitive test. Adjusted R(2) for each model ranged from 0.71–0.77 (p’s < 9.50(−10)). The relationships between all the cytokine predictors and cognitive test scores were non-linear. CONCLUSIONS: Our findings are unique to the field of CRCI and suggest non-linear cytokine specificity to neural networks underlying cognitive functions assessed in this study.

BACKGROUND AND PURPOSE: Many breast cancer survivors (BCS) experience persistent cognitive and psychological changes associated with their cancer and/or treatment and that have limited treatment options. Therefore, the purpose of this study was to explore the feasibility and effects of a Kirtan Kriya meditation (KK) intervention on cognitive and psychological symptoms compared to an attention control condition, classical music listening (ML), in BCS. MATERIALS AND METHODS: A randomized control trial design was used. Participants completed eight-week interventions. Cognitive function and psychological symptoms were measured at baseline and post-intervention. Mixed analysis of variance models were examined for all cognitive and psychological outcomes. RESULTS: 27 BCS completed the study. Intervention adherence was 88%. Both groups improved in perceived cognitive impairments, cognition related quality of life, verbal memory, and verbal fluency (p’s < 0.01). There were no significant group by time effects for cognitive and psychological outcomes, except stress. The ML group reported lower stress at time 2 (p < 0.05). CONCLUSION: KK and ML are feasible, acceptable, and cost-effective interventions that may be beneficial for survivors’ cognition and psychological symptoms. Both interventions were easy to learn, low cost, and required just 12 minutes/day. Meditation or music listening could offer providers evidence-based suggestions to BCS experiencing cognitive symptoms.

Background Persons living with HIV experience high symptom burden that can negatively impact medication adherence, work productivity, and quality of life. Symptoms are highly subjective, which can lead to under- or improper treatment. The purpose of this exploratory study was to examine relationships between circulating biomarkers representative of inflammatory, coagulation, and vascular function pathways and prevalent HIV symptoms. Setting and Sample. Adults >18 years who were diagnosed with HIV and spoke English for this cross-sectional study were recruited from community clinics and organizations. Methods Symptom burden was measured with the HIV Symptom Index; depression with the Patient Health Questionnaire. Human multiplex kits were used to determine serum concentrations of select biomarkers representing inflammatory, coagulation, and vascular function pathways. The biomarkers were included as features in machine learning models to determine which biomarkers predicted the most prevalent HIV symptoms (fatigue and muscle/joint pain) and the symptom of depression. Results Participants (N = 32) were representative of the local population of people with HIV, being mostly Black (54.4%) and male (60.6%). Depression was predicted by age, gender, glucose, hemoglobin A1c, and inflammation. Muscle/joint pain was predicted by adiponectin, C-reactive protein, and serum amyloid A (SAA). Fatigue was predicted by adiponectin, SAA, and soluble interleukin-1 receptor type II (sIL-1RII). Conclusion Biomarker clusters can be a tool to monitor symptoms. Adding an objective measure to subjective patient experiences could improve management and monitoring of symptoms. Defining a biomarker cluster for the objective assessment of HIV symptoms warrants further investigation; however, the presence of comorbid conditions needs to be controlled.

Aging, type 2 diabetes mellitus (T2DM), and cardiovascular disease are all associated with systematic low grade inflammation. Accordingly, these conditions alter circulating concentrations of cytok...

New Findings What is the central question of this study? The purpose was to determine whether acute flavanol consumption improves cerebral vasodilatory capacity during rebreathing-induced hypercapnia in African Americans. What is the main finding and its importance? The reduced cerebral vasodilatory response to hypercapnia in young healthy African Americans was improved acutely following consumption of a flavanol-rich beverage. This may have important clinical implications regarding racial differences in cerebrovascular disease risk and possible interventional approaches to offset this risk. African Americans (AAs) have increased risk for cardiovascular and cerebrovascular disease. African Americans have attenuated cerebral vasodilator capacity during hypercapnia relative to Caucasian Americans (CAs). This study tested the hypothesis, using a placebo-controlled crossover design, that acute flavanol consumption improves the range of change in cerebral vascular conductance [CVCI, (a)] and the maximal CVCI (y0) achieved during rebreathing-induced increases in end-tidal carbon dioxide tension. Fourteen college-aged AAs and 14 CAs participated. Both a and y0 were lower in AAs prior to flavanols (for a, AAs, 46 ± 16 versus CAs, 74 ± 18% CVCI, P

Introduction A high degree of interindividual variability exists in the magnitude of heat stress (HS)-induced reductions in orthostatic tolerance relative to normothermia (NT). This variability may be associated with HS-mediated reductions in cerebral perfusion (indexed as middle cerebral artery blood velocity; MCAV(mean)) and altered cerebrovascular regulation. Methods We tested the hypothesis that cerebrovascular reactivity to hypocapnia would be positively correlated with differences in tolerance to lower body negative pressure (LBNP) [assessed with a cumulative stress index (CSI)] between HS and NT (CSI(diff)). Subjects (N = 13) underwent LBNP twice (NT and HS) separated by > 72 h to assess CSI. On a third day, cerebrovascular reactivity [changes in cerebral vascular conductance (CVCi) during hyperventilation-induced hypocapnia (indexed by end tidal carbon dioxide; P(ET)CO2)] was assessed during NT, HS, and HS+LBNP (-20 mmHg; HS(LBNP)). Results Tolerance to LBNP was reduced after a 1.5 +/- 0.1 degrees C increase in internal temperature and a high degree of variability was observed for CSI(diff) (range: 122 to 1826 mmHg x min(-1)). The magnitude of reduction in CVCi during voluntary hyperventilation-induced hypocapnia (-16 +/- 5 Torr) was attenuated during HS and HS(LBNP) VS. NT (NT: -0.20 +/- 0.09 cm x s(-1) x mmHg(-1); HS: -0.12 +/- 0.09 cm x s(-1) x mmHg(-1); HS(LBNP): -0.11 +/- 0.11 cm x s(-1). mmHg(-1)); however, no relationship existed between deltaCVCi/ P(ET)CO2 and CSI(diff) in any condition. Conclusions Cerebrovascular reactivity to hyperventilation-induced hypocapnia is attenuated when internal temperature is elevated, perhaps as a protective mechanism to protect against further reductions in the already diminished cerebral perfusion in this thermal state. However, individual differences in these responses do not appear to predict orthostatic tolerance during HS.

Summary Flow-mediated dilation (FMD) is a surrogate marker for endothelial function. In the FMD procedure, arterial response during cuff inflation is not taken into consideration yet studies have demonstrated vasoconstriction, vasodilation and no change in the brachial artery during cuff inflation. The term low flow-mediated constriction (L-FMC) has been introduced to describe the vasoconstriction that occurs in some individuals during inflation of the cuff. The aims of this study were to examine (i) whether brachial artery response during cuff inflation differed in a population with varied coronary artery disease (CAD) risk factor profiles, (ii) the impact of this response on the subsequent calculation of FMD and (iii) the role of arterial stiffness in this variable response. L-FMC, ‘traditional’ FMD and ‘modified’ FMD, which accounts for brachial artery response during cuff inflation, were studied in a total of 46 subjects varying in risk factor profiles for coronary artery disease. During cuff inflation, brachial artery responses varied widely from −5·6% (vasoconstriction) to 5·0% (vasodilation). When subjects were divided into healthy versus multiple risk factors (n = 34), L-FMC and FMD were not different between the groups but modified FMD was significantly different (P = 0·02). L-FMC was modestly but significantly associated with FMD (r = 0·41) and positively correlated with brachial artery pulse wave velocity (r = 0·30). Our results indicate that brachial artery responses to inflation of the cuff are very variable and are associated with arterial stiffness and that accounting for so-called L-FMC may provide a more comprehensive assessment of endothelial vasodilatory function.

Resistance exercise involves muscular contractions that can render downstream tissues ischemic and may precondition the vasculature against ischemia–reperfusion (IR) injury, but it is unknown if habitual resistance exercise protects against IR injury in humans. We determined the magnitude and recovery from endothelial IR injury induced by forearm occlusion in 22 healthy young sedentary and resistance-trained adults. After IR injury, brachial artery flow-mediated dilation (FMD) significantly decreased by 36% in sedentary, but not resistance-trained subjects and fully recovered within 45min. Though HDL-cholesterol, handgrip strength and systolic blood pressure were significantly associated with FMD 15min after IR injury, the change in FMD from before to 15min after IR injury was not associated with any subject characteristics. These results are consistent with the notion that habitual resistance exercise may protect against endothelial IR injury in young adults, presumably through effects analogous to ischemic preconditioning.

Cerebrovascular reactivity represents the capacity of the cerebral circulation to raise blood flow in the face of increased demand, and may be reduced in some clinical and physiological conditions. We tested the hypothesis that the hypercapnia-induced increase in cerebral perfusion is attenuated during heat stress (HS) compared to normothermia (NT), and this response is further reduced during the combined challenges of HS and lower body negative pressure (LBNP).Ten healthy individuals (9 men) undertook rebreathing-induced hypercapnia during NT, HS, and HS + 20 mmHg LBNP (HSLBNP), while cerebral perfusion was indexed from middle cerebral artery blood velocity (MCA V mean). Cerebrovascular responses were calculated from the slope of the change in MCA V mean and cerebral vascular conductance (CVCi) relative to the increase in end tidal carbon dioxide ([Formula: see text]) during rebreathing.MCA V mean was similar in HS (55 ± 19 cm s(-1)) and HSLBNP (52 ± 16 cm s(-1)), and both values were reduced relative to NT (66 ± 20 cm s(-1)), yet the rise in MCA V mean per Torr increase in [Formula: see text] during rebreathing was similar in each condition (NT: 2.5 ± 0.6 cm s(-1) Torr(-1); HS: 2.4 ± 0.8 cm s(-1) Torr(-1); HSLBNP: 2.1 ± 1.1 cm s(-1) Torr(-1)). Likewise, the rate of increase in CVCi was not different between conditions (NT: 2.1 ± 0.65 cm s(-1 )mmHg(-1)100 Torr(-1); HS: 2.4 ± 0.8 cm s(-1) mmHg(-1) 100 Torr(-1); HSLBNP: 2.0 ± 1.0 cm s(-1) mmHg(-1) 100 Torr(-1)).These data indicate that cerebrovascular reactivity is not compromised during whole-body heat stress alone or when combined with mild orthostatic stress relative to normothermic conditions.

Obesity is linked with numerous physiological impairments; however, its impact on orthostatic tolerance (OT) remains unknown. This study tested the hypothesis that OT is reduced in obese individuals, and that reduced heart rate (HR) reserve and impaired cerebral autoregulation contribute to impaired OT.Eleven obese (8 females) and 22 non-obese (10 females) individuals were exposed to incremental lower body negative pressure (LBNP) to presyncope while HR, arterial blood pressure, and cerebral perfusion (middle cerebral artery blood velocity; MCA V mean) were measured. OT was quantified with a cumulative stress index (CSI).OT was reduced in obese subjects, and there was an inverse relationship between body mass index (BMI) and OT (R = -0.47). HR was higher at rest and during each level of LBNP completed by all subjects. Similar peak HR (HRpeak) during LBNP between obese and non-obese subjects resulted in obese having a higher %peak HR at rest and at each stage of LBNP compared. Relationships existed for BMI and resting %HRpeak (R = 0.45) and resting %HRpeak and CSI (R = -0.52). Despite lower CSI in obese, MCA V mean and indices of cerebral autoregulation were similar between groups at all time points.These data suggest that OT is reduced in obese and a higher resting HR, but not impaired regulation of cerebral perfusion, may contribute to this reduction.

African Americans (AA) are at an increased risk for cardio and cerebral vascular disease relative to Caucasians (CA) and the underlying impairments manifest as early as the second generation prior to overt signs of risk. The mechanisms of this increased risk are multifactorial; however, evidence suggests that microvascular dysfunction is a primary contributor. This study tested the hypothesis that microvascular function, indexed by the skin vascular conductance (SkVc) response to local heating, is impaired in young otherwise healthy AAs. Furthermore, we hypothesized that AAs have an attenuated cerebral vasodilator response to hypercapnia. To date complete data sets have has been collected on 5 AAs and 6 CAs. SkVc was assessed while the skin was clamped at 34 °C and 40 °C and values were normalized to a maximal value obtained during heating at 43 °C for 30 min. Cerebral vasomotor reactivity (CVMR) was assessed by increases in cerebral vascular conductance (CVC) during a rebreathing protocol. SkVc was reduced in the AAs at 34 °C (AA: 10±3 % max vs. CA: 20±8 % max; P=0.01) while there was a trend for CVC to be reduced at 40 °C (AA: 56±18 % max vs. CA: 71±8 % max; P=0.09). CVMR was significantly reduced during hypercapnic rebreathing in the AAs relative to the CAs (AA: 2.7±0.7 % / Torr vs. CA: 4.0±1.1 % / Torr; P=0.01). Despite the small sample size, these data suggest that microvascular function is impaired in young otherwise healthy AAs.

The mechanisms responsible for heat stress-induced reductions in tolerance to a simulated hemorrhage are unclear. Although a high degree of variability exists in the level of reduction in tolerance amongst individuals, syncope will always occur when cerebral perfusion is inadequate. This study tested the hypothesis that the magnitude of reduction in cerebral perfusion during heat stress is related to the reduction in tolerance to a lower body negative pressure (LBNP) challenge. On different days (one during normothermia and the other after a 1.5°C rise in internal temperature), 20 individuals were exposed to a LBNP challenge to presyncope. Tolerance was quantified as a cumulative stress index, and the difference in cumulative stress index between thermal conditions was used to categorize individuals most (large difference) and least (small difference) affected by the heat stress. Cerebral perfusion, as indexed by middle cerebral artery blood velocity, was reduced during heat stress compared with normothermia ( P < 0.001); however, the magnitude of reduction did not differ between groups ( P = 0.51). In the initial stage of LBNP during heat stress (LBNP 20 mmHg), middle cerebral artery blood velocity and end-tidal Pco2 were lower; whereas, heart rate was higher in the large difference group compared with small difference group ( P < 0.05 for all). These data indicate that variability in heat stress-induced reductions in tolerance to a simulated hemorrhage is not related to reductions in cerebral perfusion in this thermal condition. However, responses affecting cerebral perfusion during LBNP may explain the interindividual variability in tolerance to a simulated hemorrhage when heat stressed.

BACKGROUND AND OBJECTIVES Ankle-brachial index (ABI) is currently recommended for the screening of peripheral arterial disease. However, this method becomes less reliable in the presence of calcified, incompressible arteries, as they result in an erroneously elevated ABI, and an additional measure termed the toe-brachial index (TBI) is recommended. The evaluation of ABI, and in particular TBI, typically requires significant technical skill and often involves referral to a vascular laboratory. This present situation reveals the need for a valid and reliable, automatic, noninvasive device that will provide both ABI and TBI at the level of the primary care physician. The aim of this study was to evaluate the accuracy and reliability of such a device, the Vasera VS-1500AT, in the assessment of toe, ankle, and brachial systolic blood pressures. MATERIALS AND METHODS This study involved the assessment of 80 limbs from 40 normotensive and hypertensive individuals (17 men and 23 women) with a mean age of 45 ± 18 years. RESULTS There was a statistically significant correlation (r=0.92) between toe systolic blood pressures obtained manually with photoplethysmography compared with those obtained through the automated device. The same significant correlation was also seen between the two with ankle (r=0.87) and brachial (r=0.88) systolic blood pressures. CONCLUSION These strong correlations demonstrate that further investigation of this device is warranted regarding its use as a screening tool for the assessment of peripheral arterial disease. The automation provided by this device could potentially eliminate variability in these measurements thereby allowing for screening and diagnosis to be done without referral to a vascular laboratory.

Advancing age is a major risk factor for coronary artery disease. Endothelial dysfunction accompanied by increased oxidative stress and inflammation with aging may predispose older arteries to greater ischemia-reperfusion (I/R) injury. Because coronary artery ischemia cannot be induced safely, the effects of age and habitual endurance exercise on endothelial I/R injury have not been determined in humans. Using the brachial artery as a surrogate model of the coronary arteries, endothelial function, assessed by brachial artery flow-mediated dilation (FMD), was measured before and after 20 min of continuous forearm occlusion in young sedentary ( n = 10, 24 ± 2 yr) and middle-aged ( n = 9, 48 ± 2 yr) sedentary adults to gain insight into the effects of primary aging on endothelial I/R injury. Young ( n = 9, 25 ± 1 yr) and middle-aged endurance-trained ( n = 9, 50 ± 2 yr) adults were also studied to determine whether habitual exercise provides protection from I/R injury. Fifteen minutes after ischemic injury, FMD decreased significantly by 37% in young sedentary, 35% in young endurance-trained, 68% in middle-aged sedentary, and 50% in middle-aged endurance-trained subjects. FMD returned to baseline levels within 30 min in young sedentary and endurance-trained subjects but remained depressed in middle-aged sedentary and endurance-trained subjects. Circulating markers of antioxidant capacity and inflammation were not related to FMD. In conclusion, advancing age is associated with a greater magnitude and delayed recovery from endothelial I/R injury in humans. Habitual endurance exercise may provide partial protection to the endothelium against this form of I/R injury with advancing age.