The effects of local versus systemic passive heating on the acute inflammatory, vascular and glycaemic response.

The aim of this study was to compare the acute cardiometabolic and perceptual responses between local and whole-body passive heating. Using a water-perfused suit, 10 recreationally active males underwent three 90 min conditions: heating of the legs with upper-body cooling (LBH), whole-body heating (WBH) and exposure to a thermoneutral temperature (CON). Blood samples were collected before and up to 3 h post-session to assess inflammatory markers, while a 2 h oral glucose tolerance test was initiated 1 h post-session. Femoral artery blood flow and perceptual responses were recorded at regular intervals. The interleukin (IL)-6 incremental area under the curve (iAUC) was higher for LBH (1096 ± 851 pg/mL × 270 min) and WBH (833 ± 476 pg/mL × 270 min) compared with CON (565 ± 325 pg/mL × 270 min; p < 0.047). Glucose concentrations were higher after WBH compared with LBH and CON (p < 0.046). Femoral artery blood flow was higher at the end of WBH (1713 ± 409 mL/min) compared with LBH (943 ± 349 mL/min; p < 0.001), and higher in LBH than CON (661 ± 222 mL/min; p = 0.002). Affect and thermal comfort were more negative during WBH compared with LBH and CON (p < 0.010). In conclusion, local passive heating elevated blood flow and the IL-6 iAUC. However, while resulting in more positive perceptual responses, the majority of the included cardiometabolic markers were attenuated compared with WBH. Novelty: The increase in the IL-6 iAUC in response to passive heating is not reduced by upper-body cooling. Upper-body cooling attenuates the plasma nitrite, IL-1ra and femoral artery blood flow response to passive heating. Upper-body cooling leads to more positive perceptual responses to passive heating.

Acute Dietary Nitrate Supplementation Improves Flow Mediated Dilatation of the Superficial Femoral Artery in Healthy Older Males.

Aging is often associated with reduced leg blood flow, increased arterial stiffness, and endothelial dysfunction, all of which are related to declining nitric oxide (NO) bioavailability. Flow mediated dilatation (FMD) and passive leg movement (PLM) hyperaemia are two techniques used to measure NO-dependent vascular function. We hypothesised that acute dietary nitrate (NO3-) supplementation would improve NO bioavailability, leg FMD, and PLM hyperaemia. Fifteen healthy older men (69 ± 4 years) attended two experiment sessions and consumed either 140 mL of concentrated beetroot juice (800 mg NO3-) or placebo (NO3--depleted beetroot juice) in a randomised, double blind, cross-over design study. Plasma nitrite (NO2-) and NO3-, blood pressure (BP), augmentation index (AIx75), pulse wave velocity (PWV), FMD of the superficial femoral artery, and PLM hyperaemia were measured immediately before and 2.5 h after consuming NO3- and placebo. Placebo had no effect but NO3- led to an 8.6-fold increase in plasma NO2-, which was accompanied by an increase in FMD (NO3-: +1.18 ± 0.94% vs. placebo: 0.23 ± 1.13%, p = 0.002), and a reduction in AIx75 (NO3-: -8.7 ± 11.6% vs. placebo: -4.6 ± 5.5%, p = 0.027). PLM hyperaemia, BP, and PWV were unchanged during both trials. This study showed that a dose of dietary NO3- improved NO bioavailability and enhanced endothelial function as measured by femoral artery FMD. These findings provide insight into the specific central and peripheral vascular responses to dietary NO3- supplementation in older adults.

Martial arts technique for control of severe external bleeding.

OBJECTIVES: Haemorrhage control is a critical component of preventing traumatic death. Other than the battlefield, haemostatic devices, such as tourniquets or bandages, may not be available, allowing for significant avoidable blood loss. We hypothesised that compression of vascular pressure points using a position adapted from the martial art of Brazilian Jiu-Jitsu could be adapted to decrease blood flow velocity in major extremity arteries. METHODS: Knee mount compression was applied to the shoulder, groin and abdomen of healthy adult volunteer research subjects from Seattle, Washington, USA, from March through May 2018. Mean arterial blood flow velocity (MAV) was measured using ultrasound in the brachial and femoral arteries before and after compression. A MAV decrease greater than 20% with compression was deemed clinically relevant. RESULTS: For 11 subjects, median (IQR) MAV combining all anatomical locations tested was 29.2 (34.1, 24.1) cm/s at baseline and decreased to 3.3 (0, 19.1) cm/s during compression (Wilcoxon p<0.001). MAV was significantly decreased during compression for each individual anatomical position tested (Wilcoxon p≤0.004). Per cent (95% CI) MAV reduction was significantly greater than 20% for shoulder compression at 97.5%(94% to 100%) and groin compression at 78%(56% to 100%), but was not statistically greater for abdominal compression at 35%(12% to 57%). Complete vessel occlusion was most common with compression at the shoulder (73%), followed by groin (55%) and abdomen (9%) (χ² LR, p=0.018). CONCLUSION: The Brazilian Jiu-Jitsu knee mount position can significantly decrease blood flow in major arteries of the extremities. This technique may be useful for bleeding control after injury.

Effects of a pre-workout supplement on hyperemia following leg extension resistance exercise to failure with different resistance loads.

BACKGROUND: We sought to determine if a pre-workout supplement (PWS), containing multiple ingredients thought to enhance blood flow, increases hyperemia associated with resistance training compared to placebo (PBO). Given the potential interaction with training loads/time-under-tension, we evaluated the hyperemic response at two different loads to failure. METHODS: Thirty males participated in this double-blinded study. At visit 1, participants were randomly assigned to consume PWS (Reckless™) or PBO (maltodextrin and glycine) and performed four sets of leg extensions to failure at 30% or 80% of their 1-RM 45-min thereafter. 1-wk. later (visit 2), participants consumed the same supplement as before, but exercised at the alternate load. Heart rate (HR), blood pressure (BP), femoral artery blood flow, and plasma nitrate/nitrite (NOx) were assessed at baseline (BL), 45-min post-PWS/PBO consumption (PRE), and 5-min following the last set of leg extensions (POST). Vastus lateralis near infrared spectroscopy (NIRS) was employed during leg extension exercise. Repeated measures ANOVAs were performed with time, supplement, and load as independent variables and Bonferroni correction applied for multiple post-hoc comparisons. Data are reported as mean ± SD. RESULTS: With the 30% training load compared to 80%, significantly more repetitions were performed (p < 0.05), but there was no difference in total volume load (p > 0.05). NIRS derived minimum oxygenated hemoglobin (O2Hb) was lower in the 80% load condition compared to 30% for all rest intervals between sets of exercise (p < 0.0167). HR and BP did not vary as a function of supplement or load. Femoral artery blood flow at POST was higher independent of exercise load and treatment. However, a time*supplement*load interaction was observed revealing greater femoral artery blood flow with PWS compared to PBO at POST in the 80% (+56.8%; p = 0.006) but not 30% load condition (+12.7%; p = 0.476). Plasma NOx was ~3-fold higher with PWS compared to PBO at PRE and POST (p < 0.001). CONCLUSIONS: Compared to PBO, the PWS consumed herein augmented hyperemia following multiple sets to failure at 80% of 1-RM, but not 30%. This specificity may be a product of interaction with local perturbations (e.g., reduced tissue oxygenation levels [minimum O2Hb] in the 80% load condition) and/or muscle fiber recruitment.

Does l-citrulline supplementation improve exercise blood flow in older adults?

NEW FINDINGS: What is the central question of this study? Does short-term supplementation with l-citrulline in order to increase l-arginine improve exercise blood flow and peripheral dilatation responses to exercise in older adults? What is the main finding and its importance? l-Citrulline increased femoral blood flow by 11% and vascular conductance by 14% during lower-limb exercise in older men, whereas no changes were observed in older women. This modest improvement in bulk muscle blood flow in older men has implications for altering muscle metabolism that may result in enhanced exercise tolerance in older adults. l-Citrulline (Cit) increases l-arginine (Arg), the primary substrate for nitric oxide biosynthesis. We tested the hypothesis that muscle blood flow during exercise would be enhanced by Cit supplementation in older adults. Femoral artery blood flow was measured during calf exercise using Doppler ultrasound, and vascular conductance (FVC) was calculated in 25 older adults (13 women and 12 men) before and after 14 days of Cit (6 g day-1 ) and placebo (maltodextrin) in a randomized, double-blind, crossover study. Plasma [Arg] and resting blood pressure were also measured before and after each condition. Women and men were analysed separately because of significant sex-by-condition interactions for the change in exercise blood flow and FVC. Plasma [Arg] was increased by 30 and 35% after Cit (P < 0.01) in women and men, respectively, with no change after placebo. Citrulline lowered diastolic blood pressure in men (75 ± 9 versus 71 ± 6 mmHg, P = 0.02), but this variable remained unchanged in women. Blood flow and FVC during exercise at higher workloads were increased after Cit in men (flow, 521 ± 134 versus 584 ± 166 ml min-1 , P = 0.04; FVC, 5.0 ± 1.5 versus 5.8 ± 1.7 m, min mmHg-1 , P = 0.01) but were not different after placebo. These variables were not altered by Cit in women. Adjusting for baseline diastolic blood pressure removed (P = 0.10) the difference in FBF and FVC following Cit in men. These results indicate that l-citrulline has a modest effect of improving muscle blood flow during submaximal exercise in older men.

Passive heat therapy improves endothelial function, arterial stiffness and blood pressure in sedentary humans.

KEY POINTS: A recent 30 year prospective study showed that lifelong sauna use reduces cardiovascular-related and all-cause mortality; however, the specific cardiovascular adaptations that cause this chronic protection are currently unknown. We investigated the effects of 8 weeks of repeated hot water immersion ('heat therapy') on various biomarkers of cardiovascular health in young, sedentary humans. We showed that, relative to a sham group which participated in thermoneutral water immersion, heat therapy increased flow-mediated dilatation, reduced arterial stiffness, reduced mean arterial and diastolic blood pressure, and reduced carotid intima media thickness, with changes all on par or greater than what is typically observed in sedentary subjects with exercise training. Our results show for the first time that heat therapy has widespread and robust effects on vascular function, and as such, could be a viable treatment option for improving cardiovascular health in a variety of patient populations, particularly those with limited exercise tolerance and/or capabilities. ABSTRACT: The majority of cardiovascular diseases are characterized by disorders of the arteries, predominantly caused by endothelial dysfunction and arterial stiffening. Intermittent hot water immersion ('heat therapy') results in elevations in core temperature and changes in cardiovascular haemodynamics, such as cardiac output and vascular shear stress, that are similar to exercise, and thus may provide an alternative means of improving health which could be utilized by patients with low exercise tolerance and/or capabilities. We sought to comprehensively assess the effects of 8 weeks of heat therapy on biomarkers of vascular function in young, sedentary subjects. Twenty young, sedentary subjects were assigned to participate in 8 weeks (4-5 times per week) of heat therapy (n = 10; immersion in a 40.5°C bath sufficient to maintain rectal temperature ≥ 38.5°C for 60 min per session) or thermoneutral water immersion (n = 10; sham). Eight weeks of heat therapy increased flow-mediated dilatation from 5.6 ± 0.3 to 10.9 ± 1.0% (P < 0.01) and superficial femoral dynamic arterial compliance from 0.06 ± 0.01 to 0.09 ±0.01 mm(2)  mmHg(-1) (P = 0.03), and reduced (i.e. improved) aortic pulse wave velocity from 7.1 ± 0.3 to 6.1 ± 0.3 m s(-1) (P = 0.03), carotid intima media thickness from 0.43 ± 0.01 to 0.37 ± 0.01 mm (P < 0.001), and mean arterial blood pressure from 83 ± 1 to 78 ± 2 mmHg (P = 0.02). No changes were observed in the sham group or for carotid arterial compliance, superficial femoral intima media thickness or endothelium-independent dilatation. Heat therapy improved endothelium-dependent dilatation, arterial stiffness, intima media thickness and blood pressure, indicating improved cardiovascular health. These data suggest heat therapy may provide a simple and effective tool for improving cardiovascular health in various populations.

Prediction of all-cause death in hemodialysis patients using elevated postdialysis pulse wave velocity.

BACKGROUND: To identify the relationship between predialysis pulse wave velocity (PWV), postdialysis PWV during 1 hemodialysis (HD) session, and deaths in maintenance HD patients. METHODS: 43 patients were recruited. PWV was measured before and after one HD session and dialysis- related data were recorded. Clinical data such as blood pressure, blood lipids, and blood glucose, were carefully observed and managed in a 5-year follow-up. The association between all-cause death, predialysis PWV, postdialysis PWV, change of PWV (ΔPWV), and other related variables were analyzed. RESULTS: After 5 years, 17 patients (39.5%) died. Univariate Cox regression analysis showed that all-cause death of the patients significantly correlated with age, postdialysis PWV, and ΔPWV. Multivariate Cox regression analysis revealed that postdialysis PWV was an independent predictor for all-cause death in these patients (HR: 1.377, 95% CI: 1.146 - 1.656, p = 0.001). CONCLUSION: Elevated postdialysis PWV significantly correlated with and was an independent predictor for all-cause death in maintenance HD patients.

Effect of Chinese herbal medicine on vascular functions during 60-day head-down bed rest.

PURPOSE: Chinese herbal medicine is a promising countermeasure against cardiovascular dysfunction associated with a sedentary lifestyle. We examined the impact of the Chinese herb, Taikong Yangxin, on the micro- and macrovascular dysfunction associated with a 60-day bed rest. METHODS: Fourteen healthy men were randomly divided into two groups: those given herbal supplement, and the control group; the two groups underwent a 60-day bed rest. The macrovasculature was assessed by sonography. Skin microvascular functions were assessed with laser Doppler. The plasma level of endothelial microparticles (EMPs), markers of endothelial injury, was determined. RESULTS: Bed rest induced a 33 % decrease in the femoral artery diameter and compliance whereas carotid wall thickness, diameter, and compliance remained unchanged. The early phase of endothelium-dependent vasodilation to ACh was unmodified by bed rest, while the late phase was reduced by 30 % along with a twofold increase in EMPs. In those given Taikong Yangxin, the early phase was amplified by 2.5-fold, and the effects of bed rest on the late phase were prevented. CONCLUSION: These findings indicate that Taikong Yangxin ameliorates endothelium-dependent vasodilation, likely by improving the NO pathway. The study suggests Taikong Yangxin as a new countermeasure to prevent the changes in microvascular function induced by physical inactivity.

Effects of three postexercice recovery treatments on femoral artery blood flow kinetics.

AIM: This study aimed to compare the kinetics of muscle leg blood flow during three recovery treatments following a prolonged exercise: contrast water therapy (CWT), compression stockings (CS) or passive recovery (PR). METHODS: Fifteen men came to the laboratory three times to perform a 45-min exercise followed 5 min after by a standardized 12-min recovery treatment in upright position, alternating between two vats every 2 min: CWT (cold: ~12 °C to warm: 36 °C), CS (~20 mmHg) or PR. The order of treatments was randomized. Blood flow was measured using Doppler ultrasound during the recovery treatments (i.e., min 3, 5, 7 and 9) in the superficial femoral artery distally to the common bifurcation (~3 cm) (above the water and stocking). RESULTS: Blood flow was significantly higher during CWT (P<0.01; +22.91%) and CS (P<0.05; +15.26%) than during PR. Although no statistical difference between CWT and CS was observed, effect sizes were larger during CWT (large) than during CS (moderate). No changes in blood flow occurred in the femoral artery between hot and cold transitions of CWT. CONCLUSION: During immediate recovery of a high intensity exercise, CWT and CS trigger higher femoral artery blood flow than PR. Moreover, effect sizes were greater during CWT than during CS.

Changes in femoral artery blood flow during thermoneutral, cold, and contrast-water therapy.

AIM: The purpose of this study was to examine the changes in femoral artery blood flow during cold water immersion (CWI), contrast water therapy (CWT) and thermoneutral water immersion (TWI). METHODS: Ten athletes came to the laboratory three times, to complete a 20-min procedure in upright position: 4 min in air (baseline), then 16-min full leg TWI (~35 °C), CWI (~12 °C) or CWT (2:2 ~12 °C to ~35 °C) min ratio, in a random order. Blood flow was measured every 2 min: baseline (i.e. min 3 and 1) and throughout water immersion (i.e. min 1, 3, 5, 7, 9, 11, 13 and 15), using Doppler ultrasound in the superficial femoral artery, distal to the common bifurcation (~3 cm), above the water and stocking. RESULTS: Compared with baseline, blood flow was significantly higher throughout TWI (min 1 to 15: P<0.001; +74.6%), significantly lower during CWI (from min 7 to 15: P<0.05; -16.2%) and did not change during CWT (min 1 to 15). No changes in blood flow occurred between the hot and cold transitions of CWT. CONCLUSION: This study shows that external hydrostatic pressure (TWI ~35 °C) significantly increases femoral artery blood flow. We also show that associating hydrostatic pressure with cooling (CWI ~12 °C) decreases femoral artery blood flow after a sufficient duration, whereas associating hydrostatic pressure with alternating brief exposures to contrasted temperatures does not change femoral artery blood flow under resting conditions.

The effect of footplate neuromuscular electrical stimulation on venous and arterial haemodynamics.

OBJECTIVE: This pilot study aims to determine the effect of the Revitive™ footplate neuromuscular electrical stimulation device on venous and arterial haemodynamic changes in healthy individuals. METHOD: The blood flow (cc/min) and time averaged mean velocity (cm/s) of the superficial femoral vein and artery were measured using ultrasound at baseline, 15 min during, and immediately after cessation of the 30 min stimulation cycle. Data were analysed using the Wilcoxon matched-pairs signed rank test. RESULTS: Venous and arterial duplex ultrasound haemodynamic measurements were taken in 10 and 20 healthy volunteers, respectively. Mean age 38.7 (range 21-64), ankle brachial pressure index 0.9-1.0. At 15 min, there was a significant increase in venous median blood flow (88.3 cc/min, p = 0.014) and an increase in time averaged mean velocity (1.13 cm/s, p = 0.065) compared to baseline. Similarly, there was a significant increase in arterial median blood flow (38.7 cc/min, p < 0.0001) and time averaged mean velocity (2.21 cm/s, p = 0.0003) at 15 min compared to baseline. There was no significant difference in venous or arterial measurements compared to baseline after stimulation cessation. CONCLUSIONS: Blood flow and time averaged mean velocity increased during neuromuscular electrical stimulation but returned to baseline once stimulation had stopped. By improving blood flow, neuromuscular electrical stimulation has the ability to enhance venous return, counteract venous stasis and improve limb arterial inflow.

Elevated vascular level of ortho-tyrosine contributes to the impairment of insulin-induced arterial relaxation.

Previous studies have shown that in diabetes mellitus, insulin-induced relaxation of arteries is impaired and the level of ortho-tyrosine (o-Tyr), an oxidized amino acid is increased. Thus, we hypothesized that elevated vascular level of o-Tyr contributes to the impairment of insulin-induced vascular relaxation. Rats were fed with o-Tyr for 4 weeks. Insulin-induced vasomotor responses of isolated femoral artery were studied using wire myography. Vascular o-Tyr content was measured by HPLC, whereas immunoblot analyses were preformed to detect eNOS phosphorylation. Sustained oral supplementation of rats with o-Tyr increased the content of o-Tyr in the arterial wall and significantly reduced the relaxations to insulin. Sustained supplementation of cultured endothelial cells with o-Tyr increased the incorporation of o-Tyr and mitigated eNOS Ser (1 177) phosphorylation to insulin. Increasing arterial wall o-Tyr level attenuates insulin-induced relaxation - at least in part - by decreasing eNOS activation. Elevated level of o-Tyr could be an underlying mechanism for vasomotor dysfunction in diabetes mellitus.

Nitric oxide signalling is involved in diarylheptanoid-induced increases in femoral arterial blood flow in ovariectomized rats.

The mechanisms by which the hexane extract of Curcuma comosa increases femoral blood flow (FBF) in ovariectomized rats are not known. Thus, the aim of the present study was to investigate the acute effects and modes of action of the diarylheptanoid (3R)-1,7-diphenyl-(4E,6E)-4,6-heptadien-3-ol (D3), a phyto-oestrogen isolated from C. comosa, on FBF in ovariectomized rats. On Day 7 after ovariectomy, rats were injected once intra-arterially with D3 (100, 200, 400 and 800 µg/kg), 17ß-oestradiol (E2; 1, 2, 4 and 8 µg/kg) or vehicle. In some experiments, rats were injected with N(G)-nitro-L-arginine methyl ester (L-NAME; 10 mg/kg) 120 min after 800 µg/kg D3 or 4 µg/kg E2. In other experiments, rats were injected with 10 mg/kg L-NAME, 900 µg/kg 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) or 900 µg/kg ICI 182 780 30 min prior to the injection of 800 µg/kg D3 or 4 µg/kg E2. Mean arterial blood pressure (mABP) and FBF were recorded using a pressure transducer and a laser Doppler flow meter, respectively. Both D3 and E2 dose-dependently increased FBF without changing mABP or heart rate. The EC(50) at 120 min for D3 and E2 was 195.8 and 1.8 µg/kg, respectively. In addition, D3 and E2 dose-dependently decreased femoral vascular resistance (FVR). The EC(50) of D3 was about 100-fold greater than that of E2. The effects of D3 and E2 on FBF and FVR were diminished by intravenous injection of 10 mg/kg l-NAME. Furthermore, 30 min pretreatment with L-NAME (10 mg/kg), ODQ (900 µg/kg) or ICI 182 780 (900 µg/kg) blocked the effects of D3 and E2 on FBF and FVR. The results of the present study suggest that the phyto-oestrogen D3 increases FBF in ovariectomized rats via oestrogen receptor and nitric oxide-guanylyl cyclase signalling, which, in turn, relaxes femoral vascular resistance.

Perivagal antagonist treatment in rats selectively blocks the reflex and afferent responses of vagal lung C fibers to intravenous agonists.

The terminals of vagal lung C fibers (VLCFs) express various types of pharmacological receptors that are important to the elicitation of airway reflexes and the development of airway hypersensitivity. We investigated the blockade of the reflex and afferent responses of VLCFs to intravenous injections of agonists using perivagal treatment with antagonists (PAT) targeting the transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors in anesthetized rats. Blockading these responses via perivagal capsaicin treatment (PCT), which blocks the neural conduction of C fibers, was also studied. We used capsaicin, α,ß-methylene-ATP, and phenylbiguanide as the agonists, and capsazepine, iso-pyridoxalphosphate-6-azophenyl-2',5'-disulfonate, and tropisetron as the antagonists of transient receptor potential vanilloid 1, P2X, and 5-HT(3) receptors, respectively. We found that each of the PATs abolished the VLCF-mediated reflex apnea evoked by the corresponding agonist, while having no effect on the response to other agonists. Perivagal vehicle treatment failed to produce any such blockade. These blockades had partially recovered at 3 h after removal of the PATs. In contrast, PCT abolished the reflex apneic response to all three agonists. Both PATs and PCT did not affect the myelinated afferent-mediated apneic response to lung inflation. Consistently, our electrophysiological studies revealed that each of the PATs prevented the VLCF responses to the corresponding agonist, but not to any other agonist. PCT inevitably prevented the VLCF responses to all three agonists. Thus these PATs selectively blocked the stimulatory action of corresponding agonists on the VLCF terminals via mechanisms that are distinct from those of PCT. PAT may become a novel intervention for studying the pharmacological modulation of VLCFs.

Dietary nitrate supplementation improves revascularization in chronic ischemia.

BACKGROUND: Revascularization is an adaptive repair mechanism that restores blood flow to undersupplied ischemic tissue. Nitric oxide plays an important role in this process. Whether dietary nitrate, serially reduced to nitrite by commensal bacteria in the oral cavity and subsequently to nitric oxide and other nitrogen oxides, enhances ischemia-induced remodeling of the vascular network is not known. METHODS AND RESULTS: Mice were treated with either nitrate (1 g/L sodium nitrate in drinking water) or sodium chloride (control) for 14 days. At day 7, unilateral hind-limb surgery with excision of the left femoral artery was conducted. Blood flow was determined by laser Doppler. Capillary density, myoblast apoptosis, mobilization of CD34(+)/Flk-1(+), migration of bone marrow-derived CD31(+)/CD45(-), plasma S-nitrosothiols, nitrite, and skeletal tissue cGMP levels were assessed. Enhanced green fluorescence protein transgenic mice were used for bone marrow transplantation. Dietary nitrate increased plasma S-nitrosothiols and nitrite, enhanced revascularization, increased mobilization of CD34(+)/Flk-1(+) and migration of bone marrow-derived CD31(+)/CD45(-) cells to the site of ischemia, and attenuated apoptosis of potentially regenerative myoblasts in chronically ischemic tissue. The regenerative effects of nitrate treatment were abolished by eradication of the nitrate-reducing bacteria in the oral cavity through the use of an antiseptic mouthwash. CONCLUSIONS: Long-term dietary nitrate supplementation may represent a novel nutrition-based strategy to enhance ischemia-induced revascularization.

[Preliminary research into the relation between characteristic parameters of transesophageal photoelectric pulse wave in descending aorta and ambulatory artery blood pressure].

The present paper aims to investigate the relation between characteristic parameters of transesophageal photoelectric pulse wave in descending aorta and ambulatory artery blood pressure. The chests of ten adult experimental dogs were performed to take the photoelectric pulse wave of descending aorta transesophageally. The concurrent femoral artery invasive blood pressure was recorded simultaneously. Stepwise regression analysis method was used to study the correlation efficient between characteristic parameters of descending aorta pulse wave (H, h, h/H, g/H, At, s, H(1 + ts/td), k)and invasive artery blood pressure. The characteristic parameters, k and h/H (ratio: 90% and 80%) was proved that they had good correlation with systolic pressure; and k, H and s (ratio: 90%, 80% and 70%), had good correlation with diastolic pressure; while k and H (ratio: 90% for both) had good correlation with mean pressure. The mean values of multiple correlation coefficients of the selected characteristic parameters of descending aorta pulse wave with systolic pressure, diastolic pressure and mean pressure of femoral artery were 0.871, 0.900 and 0.856, respectively. The characteristic parameters of descending aorta pulse wave had specific correlation with systolic pressure, diastolic pressure and mean pressure.

Brain GLP-1 signaling regulates femoral artery blood flow and insulin sensitivity through hypothalamic PKC-δ.

OBJECTIVE: Glucagon-like peptide 1 (GLP-1) is a gut-brain hormone that regulates food intake, energy metabolism, and cardiovascular functions. In the brain, through a currently unknown molecular mechanism, it simultaneously reduces femoral artery blood flow and muscle glucose uptake. By analogy to pancreatic ß-cells where GLP-1 activates protein kinase C (PKC) to stimulate insulin secretion, we postulated that PKC enzymes would be molecular targets of brain GLP-1 signaling that regulate metabolic and vascular function. RESEARCH DESIGN AND METHODS: We used both genetic and pharmacological approaches to investigate the role of PKC isoforms in brain GLP-1 signaling in the conscious, free-moving mouse simultaneous with metabolic and vascular measurements. RESULTS: In normal wild-type (WT) mouse brain, the GLP-1 receptor (GLP-1R) agonist exendin-4 selectively promotes translocation of PKC-δ (but not -ßII, -α, or -ε) to the plasma membrane. This translocation is blocked in Glp1r(-/-) mice and in WT mice infused in the brain with exendin-9, an antagonist of the GLP-1R. This mechanism coordinates both blood flow in the femoral artery and whole-body insulin sensitivity. Consequently, in hyperglycemic, high-fat diet-fed diabetic mice, hypothalamic PKC-δ activity was increased and its pharmacological inhibition improved both insulin-sensitive metabolic and vascular phenotypes. CONCLUSIONS: Our studies show that brain GLP-1 signaling activates hypothalamic glucose-dependent PKC-δ to regulate femoral artery blood flow and insulin sensitivity. This mechanism is attenuated during the development of experimental hyperglycemia and may contribute to the pathophysiology of type 2 diabetes.

Systemic inflammation and carotid diameter in obese patients: pilot comparative study with flaxseed powder and cassava powder.

BACKGROUND: Botanical omega-3 fatty acid (alphalinolenic acid/ALA) has been shown to alleviate the prothrombotic and proinflammatory profile of metabolic syndrome, however clinical protocols are still scarce. Aiming to focus an obese population, a pilot study was designed. METHODS: Morbidly obese candidates for bariatric surgery (n = 29, age 46.3 ± 5.2 years), 82.8% females (24/29), BMI 44.9 ± 5.2 kg/m², with C-reactive protein/CRP > 5 mg/L were recruited. Twenty were randomized and after exclusions, 16 were available for analysis. Flaxseed powder (60 g/day, 10 g ALA) and isocaloric roasted cassava powder (60 g/day, fat-free) were administered in a double-blind routine for 12 weeks. RESULTS: During flaxseed consumption neutrophil count decreased and fibrinogen, complement C4, prothrombin time and carotid diameter remained stable, whereas placebo (cassava powder) was associated with further elevation of those measurements. CONCLUSIONS: Inflammatory and coagulatory markers tended to exhibit a better outlook in the flaxseed group. Also large-artery diameter stabilized whereas further increase was noticed in controls. These findings raise the hypothesis of a less deleterious cardiovascular course in seriously obese subjects receiving a flaxseed supplement.

Reduction of arterial graft smooth muscle mass by moderate heat therapy.

Radial artery (RA) graft spasm is a major cause of early graft failure in coronary artery bypass grafting surgeries. We explored the feasibility of thermal reduction of smooth muscle mass to attenuate vasoconstriction. Rat and rabbit femoral arteries were treated thermally in situ (45°C to 65°C; 0 s to 120 s) and then excised at various time points for histological and physiological study (pressure-diameter relationships). Human radial arteries were treated in vitro and studied in similar fashion. Weeks after thermal treatment, no overt indication was noted of vasospasm, thrombosis, or scarring in the arterial wall; however, this intervention led to a thermal dose-dependent reduction of vasoconstriction (to phenylephrine or potassium chloride) and to a conspicuous loss of smooth muscle. Pressure-diameter relationships showed no aneurismal dilation of these demuscularized arteries up to 200 mmHg. Qualitatively identical results were obtained in human radial arteries. Thermal ablation of RAs may provide a simple, safe, and effective solution to postsurgical vasospasm.

Effects of cyclic flexure on endothelial permeability and apoptosis in arterial segments perfused ex vivo.

Certain arteries (e.g., coronary, femoral, etc.) are exposed to cyclic flexure due to their tethering to surrounding tissue beds. It is believed that such stimuli result in a spatially variable biomechanical stress distribution, which has been implicated as a key modulator of remodeling associated with atherosclerotic lesion localization. In this study we utilized a combined ex vivo experimental/computational methodology to address the hypothesis that local variations in shear and mural stress associated with cyclic flexure influence the distribution of early markers of atherogenesis. Bilateral porcine femoral arteries were surgically harvested and perfused ex vivo under pulsatile arterial conditions. One of the paired vessels was exposed to cyclic flexure (0-0.7 cm(-1)) at 1 Hz for 12 h. During the last hour, the perfusate was supplemented with Evan's blue dye-labeled albumin. A custom tissue processing protocol was used to determine the spatial distribution of endothelial permeability, apoptosis, and proliferation. Finite element and computational fluid dynamics techniques were used to determine the mural and shear stress distributions, respectively, for each perfused segment. Biological data obtained experimentally and mechanical stress data estimated computationally were combined in an experiment-specific manner using multiple linear regression analyses. Arterial segments exposed to cyclic flexure had significant increases in intimal and medial apoptosis (3.42+/-1.02 fold, p=0.029) with concomitant increases in permeability (1.14+/-0.04 fold, p=0.026). Regression analyses revealed specific mural stress measures including circumferential stress at systole, and longitudinal pulse stress were quantitatively correlated with the distribution of permeability and apoptosis. The results demonstrated that local variation in mechanical stress in arterial segments subjected to cyclic flexure indeed influence the extent and spatial distribution of the early atherogenic markers. In addition, the importance of including mural stresses in the investigation of vascular mechanopathobiology was highlighted. Specific example results were used to describe a potential mechanism by which systemic risk factors can lead to a heterogeneous disease.