Differential engagement of inhibitory and excitatory cardiopulmonary reflexes by capsaicin and phenylbiguanide in C57BL/6 mice.

The Bezold-Jarisch reflex is a powerful inhibitory reflex initiated by activation of cardiopulmonary vagal nerves during myocardial ischemia, hemorrhage, and orthostatic stress leading to bradycardia, vasodilation, hypotension, and vasovagal syncope. This clinically relevant reflex has been studied by measuring heart rate (HR) and mean arterial pressure (MAP) responses to injections of a variety of chemical compounds. We hypothesized that reflex responses to different compounds vary due to differential activation of vagal afferent subtypes and/or variable coactivation of excitatory afferents. HR and MAP responses to intravenous injections of the transient receptor potential vanilloid-1 (TRPV1) agonist capsaicin and the serotonin 5-HT3 receptor agonist phenylbiguanide (PBG) were measured in anesthetized C57BL/6 mice before and after bilateral cervical vagotomy. Capsaicin and PBG evoked rapid dose-dependent decreases in HR and MAP followed by increases in HR and MAP above baseline. Bezold-Jarisch reflex responses were abolished after vagotomy, whereas the delayed tachycardic and pressor responses to capsaicin and PBG were differentially enhanced. The relative magnitude of bradycardic versus depressor responses (↓HR/↓MAP) in vagus-intact mice was greater with capsaicin. In contrast, after vagotomy, the magnitude of excitatory tachycardic versus pressor responses (↑HR/↑MAP) was greater with PBG. Although capsaicin-induced increases in MAP and HR postvagotomy were strongly attenuated or abolished after administration of the ganglionic blocker hexamethonium, PBG-induced increases in MAP and HR were mildly attenuated and unchanged, respectively. We conclude that responses to capsaicin and PBG differ in mice, with implications for delineating the role of endogenous agonists of TRPV1 and 5-HT3 receptors in evoking cardiopulmonary reflexes in pathophysiological states.

A meta-analysis on the effect of proximal landing zone location on stroke and mortality in thoracic endovascular aortic repair.

BACKGROUND: Thoracic endovascular aortic repair (TEVAR) involving the aortic arch may increase the opportunity for stroke owing to disruption of cerebral circulation and embolization. In this study, a systematic meta-analysis was performed to examine the impact of proximal landing zone location on stroke and 30-day mortality after TEVAR. METHODS: MEDLINE and Cochrane Library were searched for all original studies of TEVAR reporting outcomes of stroke or 30-day mortality for at least two adjacent proximal landing zones, based on the Ishimaru classification scheme. Forest plots were created using relative risks (RR) with 95% confidence intervals (CI). An I2 of <40% was regarded as minimal heterogeneity. A P value of <.05 was considered significant. RESULTS: Of the 57 studies examined, a total of 22,244 patients (male 73.1%, aged 71.9 ± 11.5 years) were included in the meta-analysis, with 1693 undergoing TEVAR with proximal landing zone 0, 1931 with zone 1, 5839 with zone 2, and 3089 with zone 3 and beyond. The overall risk of clinically evident stroke was 2.7% for zones ≥3, 6.6% for zone 2, 7.7% for zone 1, and 14.2% for zone 0. More proximal landing zones were associated with higher risks of stroke compared with distal (zone 2 vs ≥3: RR, 2.14; 95% CI, 1.43-3.20; P = .0002; I2 = 56%; zone 1 vs 2: RR, 1.48; 95% CI, 1.20-1.82; P = .0002; I2 = 0%; zone 0 vs 1: RR, 1.85; 95% CI, 1.52-2.24; P < .00001; I2 = 0%). Mortality at 30 days was 2.9% for zones ≥3, 2.4% for zone 2, 3.7% for zone 1, and 9.3% for zone 0. Zone 0 was associated with higher mortality compared with zone 1 (RR, 2.30; 95% CI, 1.75-3.03; P < .00001; I2 = 0%). No significant differences were found in 30-day mortality between zones 1 and 2 (P = .13) and between zone 2 and zones ≥3 (P = .87). CONCLUSIONS: The risk of stroke from TEVAR is lowest in zone 3 and beyond, increasing significantly as the landing zone is moved proximally. Furthermore, perioperative mortality is increased with zone 0 compared with zone 1. Therefore, risk of stent grafting in the proximal arch should be weighed against alternative surgical or nonoperative options. It is anticipated that the risk of stroke will improve with further development of stent graft technology and implantation technique.

Elevated Risk Analysis Index (RAI) Frailty Scores Are Independently Associated with Adverse Outcomes in Lower Extremity Surgical Revascularizations Similarly Across Genders.

BACKGROUND: The Risk Analysis Index (RAI) frailty scoring system has recently undergone revision and external validation using the National Surgical Quality Improvement Program (NSQIP) database. We set forth to evaluate the association of RAI-rev ranges with outcomes following lower extremity surgical revascularization and verify equivalent applicability across genders. METHODS: All elective NSQIP Targeted Lower Extremity Open cases from 2015-2019 were divided by EMR-recorded gender. Aggregate demographics, perioperative factors, and 30-day outcomes were compared using unpaired t-test and Fisher's exact test. Adjusted odds-ratios (aOR) for each outcome were generated by applying a multivariate binary logistic regression model (IBM SPSSTM) for five-point RAI-rev score increments from 25-45 and a most-frail group with scores >45 with a non-frail reference of <25. Covariates included surgical indication, prior ipsilateral revascularization, graft utilization, dirty/infected wound, smoking, hypertension, diabetes, and steroid use. RESULTS: 8,155 cases included 2,498 (31%) performed in women who demonstrated slightly lower RAI-rev scores than men (22.1 ± 5.8 vs. 24.2 ± 5.1; P = 0.0001). Univariate trends demonstrated dose-dependent increases in frequency of most outcomes with rising frailty score ranges, most substantially regarding mortality (0.4% non-frail to 14.7% most-frail), disposition to skilled nursing facility (8% non-frail to 27% most-frail), and extended length of stay (16% non-frail to 44% most-frail). After adjusting for co-variates, patients with RAI-rev scores of 26-30 had aOR of 1.4 (95% CI: 1.2-1.6; P < 0.001), 1.9 (95% CI: 1.6-2.2; P < 0.001), and 2.4 (95% CI:1.3-4.4; P < 0.001) for extended stay, disposition to skilled nursing, and mortality respectively. Trends were similar across genders in both univariate and multivariate analyses. CONCLUSIONS: Mortality, extended stay, and increased rehabilitation needs after surgical revascularization were associated with higher RAI-rev score ranges in a dose dependent manner similarly across genders.

Analysis of a Novel Inpatient Acute Limb Ischemia Alert System.

OBJECTIVES: Acute limb ischemia (ALI) is a surgical emergency that generally develops in the outpatient setting. Hospitalized patients are also at risk for acute limb ischemia, but their presentation may be atypical or altered by medical therapy. Our institution developed an alert system to facilitate the prompt recognition and treatment of ALI that occurs in the inpatient population. We aimed to evaluate the usage of the system after the first 2 years of operation. METHODS: All ALI alerts from October 2017 to December 2019 were collected from paging records and analyzed for location, timing, and the need for intervention. Alerts undergoing vascular intervention were classified as urgent (within 8 hours) or delayed (after 8 hr). Time and location data were evaluated to determine patterns of usage and true-positive rate of the system. RESULTS: From October 2017 to December 2019, there were 237 ALI alerts obtained from paging records containing time and location information for the alert. More alerts originated from ICUs relative to non-ICU floors (68% vs. 33%, P< 0.001), however a greater proportion of non-ICU floor alerts required intervention compared to ICU alerts (32.0% vs. 5.1%, P < .0001). The highest number of ALI alerts were from the Medical ICU (MRICU) (45.9%) and medical/surgical floors (33.3%), followed by Surgical ICU (20.2%). Alerts were more common within 3 hr of morning and evening nursing shift changes (47.3%, P < 0.001). From the 237 total alerts, the patient was able to be identified retrospectively in 186 cases, and of these 27 resulted in operative interventions (14.5%, positive predictive value), with 11 patients (40.7%) requiring urgent intervention with a median time to intervention of 3.5 hr (range 2.2-4.8), and 16 (59%) alerts undergoing a delayed intervention at a mean of 3 days (range 2-4). A total of 73 (39.2%) alert patients died during their admission, of which 65 (89.0%) were in an ICU, and no deaths were directly related to ALI. The median time to death was 2 days (range 0-95 days), and in 22 cases death occurred <24 hr from time of alert. CONCLUSION: Our novel hospital-wide ALI alert system demonstrates a 14.5% positive predictive value for ischemia that resulted in an intervention. Alerts were more likely to originate from the ICU setting and during nursing shift changes. Alerts originating from non-ICU floors were 5 times more likely to undergo surgical intervention for ALI. Further analysis is required to assess the effect of this system on patient safety, outcome, and allocation of institutional resources.

The Application of Virtual Reality in Patient Education.

BACKGROUND: Virtual reality (VR) provides an immersive image-viewing experience that has recently been expanding in use in clinical medicine. We developed a three-dimensional (3D) model of an abdominal aortic aneurysm (AAA) for patients with a diagnosis of an AAA to view in VR to assess the use of VR in patient education. METHODS: This was a cross-sectional study using an educational intervention. A standardized 3D model of an AAA was generated from a computed tomography scan and uploaded onto a 3D image-hosting website. Patients with an AAA who participated in the study wore a Google Cardboard VR headset, with a mobile device displaying the digital 3D AAA image in VR. Patients completed a survey afterward for assessing satisfaction with VR on a 5-point agreement Likert scale. RESULTS: Between September 2017 and January 2018, 19 patients participated in our study (90% participation rate). Most participants had no prior experience with VR (n = 15; 79%), and the mean age was 69 ± 8 years. Seventeen (89%) participants agreed or strongly agreed that they felt better informed about their health status after using VR and would like to see VR used more in their health care, while sixteen (84%) agreed or strongly agreed that they felt more engaged in their health care because of using VR. Almost all participants felt comfortable using VR (n = 17; 90%) and enjoyed using the technology (n = 16; 84%). CONCLUSIONS: VR proved to be an engaging learning tool that patients perceived as beneficial in understanding their health status. Further efforts to investigate the role of VR in education and health care should be explored.

Increased activity of the orexin system in the paraventricular nucleus contributes to salt-sensitive hypertension.

The orexin system is involved in arginine vasopressin (AVP) regulation, and its overactivation has been implicated in hypertension. However, its role in salt-sensitive hypertension (SSHTN) is unknown. Here, we tested the hypothesis that hyperactivity of the orexin system in the paraventricular nucleus (PVN) contributes to SSHTN via enhancing AVP signaling. Eight-week-old male Dahl salt-sensitive (Dahl S) and age- and sex-matched Sprague-Dawley (SD) rats were placed on a high-salt (HS; 8% NaCl) or normal-salt (NS; 0.4% NaCl) diet for 4 wk. HS intake did not alter mean arterial pressure (MAP), PVN mRNA levels of orexin receptor 1 (OX1R), or OX2R but slightly increased PVN AVP mRNA expression in SD rats. HS diet induced significant increases in MAP and PVN mRNA levels of OX1R, OX2R, and AVP in Dahl S rats. Intracerebroventricular infusion of orexin A (0.2 nmol) dramatically increased AVP mRNA levels and immunoreactivity in the PVN of SD rats. Incubation of cultured hypothalamus neurons from newborn SD rats with orexin A increased AVP mRNA expression, which was attenuated by OX1R blockade. In addition, increased cerebrospinal fluid Na+ concentration through intracerebroventricular infusion of NaCl solution (4 µmol) increased PVN OX1R and AVP mRNA levels and immunoreactivity in SD rats. Furthermore, bilateral PVN microinjection of the OX1R antagonist SB-408124 resulted in a greater reduction in MAP in HS intake (-16 ± 5 mmHg) compared with NS-fed (-4 ± 4 mmHg) anesthetized Dahl S rats. These results suggest that elevated PVN OX1R activation may contribute to SSHTN by enhancing AVP signaling.NEW & NOTEWORTHY To our best knowledge, this study is the first to investigate the involvement of the orexin system in salt-sensitive hypertension. Our results suggest that the orexin system may contribute to the Dahl model of salt-sensitive hypertension by enhancing vasopressin signaling in the hypothalamic paraventricular nucleus.

Sympathoexcitation in ANG II-salt hypertension involves reduced SK channel function in the hypothalamic paraventricular nucleus.

Hypertension (HTN) resulting from subcutaneous infusion of ANG II and dietary high salt (HS) intake involves sympathoexcitation. Recently, we reported reduced small-conductance Ca(2+)-activated K(+) (SK) current and increased excitability of presympathetic neurons in the paraventricular nucleus (PVN) in ANG II-salt HTN. Here, we hypothesized that ANG II-salt HTN would be accompanied by altered PVN SK channel activity, which may contribute to sympathoexcitation in vivo. In anesthetized rats with normal salt (NS) intake, bilateral PVN microinjection of apamin (12.5 pmol/50 nl each), the SK channel blocker, remarkably elevated splanchnic sympathetic nerve activity (SSNA), renal sympathetic nerve activity (RSNA), and mean arterial pressure (MAP). In contrast, rats with ANG II-salt HTN demonstrated significantly attenuated SSNA, RSNA, and MAP (P < 0.05) responses to PVN-injected apamin compared with NS control rats. Next, we sought to examine the individual contributions of HS and subcutaneous infusion of ANG II on PVN SK channel function. SSNA, RSNA, and MAP responses to PVN-injected apamin in rats with HS alone were significantly attenuated compared with NS-fed rats. In contrast, sympathetic nerve activity responses to PVN-injected apamin in ANG II-treated rats were slightly attenuated with SSNA, demonstrating no statistical difference compared with NS-fed rats, whereas MAP responses to PVN-injected apamin were similar to NS-fed rats. Finally, Western blot analysis showed no statistical difference in SK1-SK3 expression in the PVN between NS and ANG II-salt HTN. We conclude that reduced SK channel function in the PVN is involved in the sympathoexcitation associated with ANG II-salt HTN. Dietary HS may play a dominant role in reducing SK channel function, thus contributing to sympathoexcitation in ANG II-salt HTN.

Sympathoexcitation and pressor responses induced by ethanol in the central nucleus of amygdala involves activation of NMDA receptors in rats.

The central nervous system plays an important role in regulating sympathetic outflow and arterial pressure in response to ethanol exposure. However, the underlying neural mechanisms have not been fully understood. In the present study, we tested the hypothesis that injection of ethanol in the central nucleus of the amygdala (CeA) increases sympathetic outflow, which may require the activation of local ionotropic excitatory amino acid receptors. In anesthetized rats, CeA injection of ethanol (0, 0.17, and 1.7 µmol) increased splanchnic sympathetic nerve activity (SSNA), lumbar sympathetic nerve activity (LSNA), and mean arterial pressure (MAP) in a dose-dependent manner. A cocktail containing ethanol (1.7 µmol) and kynurenate (KYN), an ionotropic excitatory amino acid receptor blocker, showed significantly blunted sympathoexcitatory and pressor responses compared with those elicited by CeA-injected ethanol alone (P < 0.01). A cocktail containing ethanol and d-2-amino-5-phosphonovalerate, an N-methyl-d-aspartate (NMDA) receptor antagonist, elicited attenuated sympathoexcitatory and pressor responses that were significantly less than ethanol alone (P < 0.01). In addition, CeA injection of acetate (0.20 µmol, n = 7), an ethanol metabolite, consistently elicited sympathoexcitatory and pressor responses, which were effectively blocked by d-2-amino-5-phosphonovalerate (n = 9, P < 0.05). Inhibition of neuronal activity of the rostral ventrolateral medulla (RVLM) with KYN significantly (P < 0.01) attenuated sympathoexcitatory responses elicited by CeA-injected ethanol. Double labeling of immune fluorescence showed NMDA NR1 receptor expression in CeA neurons projecting to the RVLM. We conclude that ethanol and acetate increase sympathetic outflow and arterial pressure, which may involve the activation of NMDA receptors in CeA neurons projecting to the RVLM.

Sleep efficiency and nocturnal hemodynamic dipping in young, normotensive adults.

Blunted dipping of nocturnal systolic arterial pressure (SAP) and heart rate (HR) are independent risk factors for hypertension and all-cause mortality. While several epidemiological studies report a significant association between short sleep duration and hypertension, associations between sleep efficiency and the nocturnal drop of SAP remain controversial. Moreover, relations between sleep efficiency and HR diurnal patterns have been overlooked. We hypothesized that low sleep efficiency (<85%) would be associated with blunted nocturnal SAP and HR dipping. Twenty-two normotensive subjects (13 men, 9 women; age: 18-28 yr) wore an actigraphy watch for 7 days and nights, and an ambulatory blood pressure monitor for 24 h on a nonactigraph night. There were no differences in age, sex, body mass index, mean sleep time, number of awakenings, or 24-h blood pressure between the low (n = 12) and high (n = 10) sleep efficiency groups. However, the low sleep efficiency subjects demonstrated a blunted dip of nocturnal SAP (10 ± 1% vs. 14 ± 1%, P = 0.04) and HR (12 ± 3% vs. 21 ± 3%, P = 0.03) compared with the high sleep efficiency group. The low sleep efficiency group also demonstrated a higher mean nocturnal HR (63 ± 2 vs. 55 ± 2 beats/min; P = 0.02). These findings support growing evidence that sleep efficiency, independent of total sleep time, may be an important cardiovascular risk factor.

Sympathetic neural responses to 24-hour sleep deprivation in humans: sex differences.

Sleep deprivation has been linked to hypertension, and recent evidence suggests that associations between short sleep duration and hypertension are stronger in women. In the present study we hypothesized that 24 h of total sleep deprivation (TSD) would elicit an augmented pressor and sympathetic neural response in women compared with men. Resting heart rate (HR), blood pressure (BP), and muscle sympathetic nerve activity (MSNA) were measured in 30 healthy subjects (age, 22 ± 1; 15 men and 15 women). Relations between spontaneous fluctuations of diastolic arterial pressure and MSNA were used to assess sympathetic baroreflex function. Subjects were studied twice, once after normal sleep and once after TSD (randomized, crossover design). TSD elicited similar increases in systolic, diastolic, and mean BP in men and women (time, P < 0.05; time × sex, P > 0.05). TSD reduced MSNA in men (25 ± 2 to 16 ± 3 bursts/100 heart beats; P = 0.02), but not women. TSD did not alter spontaneous sympathetic or cardiovagal baroreflex sensitivities in either sex. However, TSD shifted the spontaneous sympathetic baroreflex operating point downward and rightward in men only. TSD reduced testosterone in men, and these changes were correlated to changes in resting MSNA (r = 0.59; P = 0.04). Resting HR, respiratory rate, and estradiol were not altered by TSD in either sex. In conclusion, TSD-induced hypertension occurs in both sexes, but only men demonstrate altered resting MSNA. The sex differences in MSNA are associated with sex differences in sympathetic baroreflex function (i.e., operating point) and testosterone. These findings may help explain why associations between sleep deprivation and hypertension appear to be sex dependent.

Role of small conductance calcium-activated potassium channels expressed in PVN in regulating sympathetic nerve activity and arterial blood pressure in rats.

Small conductance Ca(2+)-activated K(+) (SK) channels regulate membrane properties of rostral ventrolateral medulla (RVLM) projecting hypothalamic paraventricular nucleus (PVN) neurons and inhibition of SK channels increases in vitro excitability. Here, we determined in vivo the role of PVN SK channels in regulating sympathetic nerve activity (SNA) and mean arterial pressure (MAP). In anesthetized rats, bilateral PVN microinjection of SK channel blocker with peptide apamin (0, 0.125, 1.25, 3.75, 12.5, and 25 pmol) increased splanchnic SNA (SSNA), renal SNA (RSNA), MAP, and heart rate (HR) in a dose-dependent manner. Maximum increases in SSNA, RSNA, MAP, and HR elicited by apamin (12.5 pmol, n = 7) were 330 ± 40% (P < 0.01), 271 ± 40% (P < 0.01), 29 ± 4 mmHg (P < 0.01), and 34 ± 9 beats/min (P < 0.01), respectively. PVN injection of the nonpeptide SK channel blocker UCL1684 (250 pmol, n = 7) significantly increased SSNA (P < 0.05), RSNA (P < 0.05), MAP (P < 0.05), and HR (P < 0.05). Neither apamin injected outside the PVN (12.5 pmol, n = 6) nor peripheral administration of the same dose of apamin (12.5 pmol, n = 5) evoked any significant changes in the recorded variables. PVN-injected SK channel enhancer 5,6-dichloro-1-ethyl-1,3-dihydro-2H-benzimidazol-2-one (DCEBIO, 5 nmol, n = 4) or N-cyclohexyl-N-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-4-pyrimidin]amine (CyPPA, 5 nmol, n = 6) did not significantly alter the SSNA, RSNA, MAP, and HR. Western blot and RT-PCR analysis of punched PVN tissue showed abundant expression of SK1-3 channels. We conclude that SK channels expressed in the PVN play an important role in the regulation of sympathetic outflow and cardiovascular function.

Influence of acute alcohol ingestion on sympathetic neural responses to orthostatic stress in humans.

Acute alcohol consumption is reported to decrease mean arterial pressure (MAP) during orthostatic challenge, a response that may contribute to alcohol-mediated syncope. Muscle sympathetic nerve activity (MSNA) increases during orthostatic stress to help maintain MAP, yet the effects of alcohol on MSNA responses during orthostatic stress have not been determined. We hypothesized that alcohol ingestion would blunt arterial blood pressure and MSNA responses to lower body negative pressure (LBNP). MAP, MSNA, and heart rate (HR) were recorded during progressive LBNP (-5, -10, -15, -20, -30, and -40 mmHg; 3 min/stage) in 30 subjects (age 24 ± 1 yr). After an initial progressive LBNP (pretreatment), subjects consumed either alcohol (0.8 g ethanol/kg body mass; n = 15) or placebo (n = 15), and progressive LBNP was repeated (posttreatment). Alcohol increased resting HR (59 ± 2 to 65 ± 2 beats/min, P < 0.05), MSNA (13 ± 3 to 19 ± 4 bursts/min, P < 0.05), and MSNA burst latency (1,313 ± 16 to 1,350 ± 17 ms, P < 0.05) compared with placebo (group × treatment interactions, P < 0.05). During progressive LBNP, a pronounced decrease in MAP was observed after alcohol but not placebo (group × time × treatment, P < 0.05). In contrast, MSNA and HR increased during all LBNP protocols, but there were no differences between trials or groups. However, alcohol altered MSNA burst latency response to progressive LBNP. In conclusion, the lack of MSNA adjustment to a larger drop in arterial blood pressure during progressive LBNP, coupled with altered sympathetic burst latency responses, suggests that alcohol blunts MSNA responses to orthostatic stress.

Expression of Proinflammatory Cytokines Is Upregulated in the Hypothalamic Paraventricular Nucleus of Dahl Salt-Sensitive Hypertensive Rats.

Accumulating evidence indicates that inflammation is implicated in hypertension. However, the role of brain proinflammatory cytokines (PICs) in salt sensitive hypertension remains to be determined. Thus, the objective of this study was to test the hypothesis that high salt (HS) diet increases PICs expression in the paraventricular nucleus (PVN) and leads to PVN neuronal activation. Eight-week-old male Dahl salt sensitive (Dahl S) rats, and age and sex matched normal Sprague Dawley (SD) rats were divided into two groups and fed with either a HS (4% NaCl) or normal salt (NS, 0.4% NaCl) diet for 5 consecutive weeks. HS diet induced hypertension and significantly increased cerebrospinal fluid (CSF) sodium concentration ([Na+]) in Dahl S rats, but not in normal SD rats. In addition, HS diet intake triggered increases in mRNA levels and immunoreactivities of PVN PICs including TNF-α, IL-6, and IL-1ß, as well as Fra1, a chronic marker of neuronal activation, in Dahl S rats, but not in SD rats. Next, we investigated whether this increase in the expression of PVN PICs and Fra1 was induced by increased CSF [Na+]. Adult male SD rats were intracerebroventricular (ICV) infused with 8 µl of either hypertonic salt (4 µmol NaCl), mannitol (8 µmol, as osmolarity control), or isotonic salt (0.9% NaCl as vehicle control). Three hours following the ICV infusion, rats were euthanized and their PVN PICs expression was measured. The results showed that central administration of hypertonic saline in SD rats significantly increased the expression of PICs including TNF-α, IL-6, and IL-1ß, as well as neuronal activation marker Fra1, compared to isotonic NaCl controls and osmolarity controls. Finally, we tested whether the increase in PICs expression occurred in neurons. Incubation of hypothalamic neurons with 10 mM NaCl in a culture medium for 6 h elicited significant increases in TNF-α, IL-6, and Fra1 mRNA levels. These observations, coupled with the important role of PICs in modulating neuronal activity and stimulating vasopressin release, suggest that HS intake induces an inflammatory state in the PVN, which, may in turn, augments sympathetic nerve activity and vasopressin secretion, contributing to the development of salt sensitive hypertension.

Measurement of cations, anions, and acetate in serum, urine, cerebrospinal fluid, and tissue by ion chromatography.

Accurate quantification of cations and anions remains a major diagnostic tool in understanding diseased states. The current technologies used for these analyses are either unable to quantify all ions due to sample size/volume, instrument setup/method, or are only able to measure ion concentrations from one physiological sample (liquid or solid). Herein, we adapted a common analytical chemistry technique, ion chromatography and applied it to measure the concentration of cations; sodium, potassium, calcium, and magnesium (Na+ , K+ , Ca2+ , and Mg2+ ) and anions; chloride, and acetate (Cl- , - OAc) from physiological samples. Specifically, cations and anions were measured in liquid samples: serum, urine, and cerebrospinal fluid, as well as tissue samples: liver, cortex, hypothalamus, and amygdala. Serum concentrations of Na+ , K+ , Ca2+ , Mg2+ , Cl- , and - OAc (mmol/L): 138.8 ± 4.56, 4.05 ± 0.21, 4.07 ± 0.26, 0.98 ± 0.05, 97.7 ± 3.42, and 0.23 ± 0.04, respectively. Cerebrospinal fluid concentrations of Na+ , K+ , Ca2+ , Mg2+ , Cl- , and - OAc (mmol/L): 145.1 ± 2.81, 2.41 ± 0.26, 2.18 ± 0.38, 1.04 ± 0.11, 120.2 ± 3.75, 0.21 ± 0.05, respectively. Tissue Na+ , K+ , Ca2+ , Mg2+ , Cl- , and - OAc were also measured. Validation of the ion chromatography method was established by comparing chloride concentration between ion chromatography with a known method using an ion selective chloride electrode. These results indicate that ion chromatography is a suitable method for the measurement of cations and anions, including acetate from various physiological samples.

New techniques and developments of stenting for infrainguinal arterial occlusive disease: are the results any better than balloon angioplasty alone?

Infrainguinal occlusive disease is a complex problem necessitating the cooperation of both medical and surgical therapies to aid limb salvage and alleviate symptoms. Endovascular therapies are varied, with no treatment clearly outweighing the other in terms of efficacy and durability. Angioplasty for focal stenosis has gained ground as the treatment of choice when indicated. There has also been a rapid evolution in stent technology, from early stainless steel wall stents to today's drug eluting nitinol stents. In this article, we examine the literature on these new technologies and treatment options and make recommendations based on the best data available.

High Salt Intake Augments Excitability of PVN Neurons in Rats: Role of the Endoplasmic Reticulum Ca2+ Store.

High salt (HS) intake sensitizes central autonomic circuitry leading to sympathoexcitation. However, its underlying mechanisms are not fully understood. We hypothesized that inhibition of PVN endoplasmic reticulum (ER) Ca2+ store function would augment PVN neuronal excitability and sympathetic nerve activity (SNA). We further hypothesized that a 2% (NaCl) HS diet for 5 weeks would reduce ER Ca2+ store function and increase excitability of PVN neurons with axon projections to the rostral ventrolateral medulla (PVN-RVLM) identified by retrograde label. PVN microinjection of the ER Ca2+ ATPase inhibitor thapsigargin (TG) increased SNA and mean arterial pressure (MAP) in a dose-dependent manner in rats with a normal salt (NS) diet (0.4%NaCl). In contrast, sympathoexcitatory responses to PVN TG were significantly (p < 0.05) blunted in HS treated rats compared to NS treatment. In whole cell current-clamp recordings from PVN-RVLM neurons, graded current injections evoked graded increases in spike frequency. Maximum discharge was significantly augmented (p < 0.05) by HS diet compared to NS group. Bath application of TG (0.5 µM) increased excitability of PVN-RVLM neurons in NS (p < 0.05), yet had no significant effect in HS rats. Our data indicate that HS intake augments excitability of PVN-RVLM neurons. Inhibition of the ER Ca2+-ATPase and depletion of Ca2+ store likely plays a role in increasing PVN neuronal excitability, which may underlie the mechanisms of sympathoexcitation in rats with chronic HS intake.