Mean Arterial Pressure Responses Research Articles

Muscle Sympathetic Nerve Activity and Cerebrovascular Responses to Mental Stress

Mental stress has been shown to elicit increases in arterial blood pressure, heart rate and cerebral blood flow, whereas the degree of sympathoexcitation induced by mental stress has been shown to be inconsistent. Previous studies have examined the relationship between limb vascular responsiveness and muscle sympathetic nerve activity (MSNA) during mental stress; however, this has not been studied in relation to the cerebral vasculature. The purpose of this study was to examine concurrent neural and cerebrovascular responses to mental stress. Thirteen healthy adults (men/women: 7/6; age = 28 ± 5 years; BMI = 25 ± 2 kg/m2) completed the Stroop Color Word Test. Beat‐to‐beat mean arterial pressure (MAP) using finger photoplethysmograpy, heart rate (HR) using a 3‐lead ECG, middle cerebral artery velocity (MCAv) using transcranial doppler ultrasound, and MSNA using microneurography were continuously recorded at baseline and in response to the Stroop Color Word Test. The response to the mental stress was recorded as the change from baseline. Linear regression was used to assess the influence of MSNA on cerebrovascular and hemodynamic variables. As expected, there were increases in HR (baseline = 58 ± 8 bpm vs. Stroop = 66 ± 10 bpm; p = 0.045) and MCAv (baseline = 58 ± 8 cm/s vs. Stroop = 69 ± 13 cm/s; p = 0.016) from baseline during the Stroop test. However, there was no change in MAP (baseline = 96 ± 16 mmHg vs. Stroop = 99 ± 17 mmHg; p > 0.05) or MSNA (baseline = 16 ± 6 bursts/min vs. Stroop = 17 ± 7 bursts/min; p > 0.05) from baseline during the Stroop test. Although the change in MAP was positively associated with the change in MCAv (r = 0.46, p = 0.025), there were no associations between the change in MSNA and the increase in MCAv, MAP, or HR in response to the Stroop test. In conclusion, our results demonstrate a disassociation between the MSNA, MAP and MCAv responses to mental stress. It is also possible that the temporal response to mental stress is different and future studies could examine the time course of the sympathetic and cerebrovascular responses.

Exaggerated Activities of P2X3 and ASIC3 Signaling Pathway in Muscle Afferent Following Himblimb Muscle Ischemia‐Reperfusion

BackgroundPeripheral artery disease (PAD) is one of the major cardiovascular concerns and dramatically reduces the blood flow supply in the affected limbs. A combination of revascularization surgery in the femoral artery and supervised exercise intervention is among the most general approaches for the treatment of PAD. The approach of revascularization inevitably induces ischemia‐reperfusion (IR) injury in the tissues with the reperfusion of blood flow. Notably, following muscle IR in rats, we have observed an exaggerated exercise pressor reflex (EPR) indicating a risk of cardiovascular diseases, as the increased blood pressure (BP) response during exercise. In specific, a time‐course study (18, 66 and 114 hours post‐IR) showed that an increment in BP response was most profound in 18 hours post‐IR (IR 18h) among all the time points. However the underlying molecular mechanism leading to the IR‐induced exaggerated EPR has yet poorly understood.AimsWe targeted if the hindlimb muscle IR alters the activities of two key signaling pathway in muscle afferent nerves in regulating the EPR, namely P2X3 and ASIC3.MethodsWestern blot technique was used to determine the protein expression of P2X3 and ASIC3 in L4‐6 dorsal root ganglion (DRG) of sham rats and IR 18h rats. Meanwhile, the mean arterial pressure (MAP) responses to α‐β‐me‐ATP and lactic acid intra‐arterially injected into the hindlimb were examined to assess the P2X3 and ASIC3‐mediated EPR, respectively. Whole‐cell patch clamp was applied to evaluate the P2X and ASIC3 currents in the isolated muscle DRG neurons in both sham and IR 18h rats. All data were presented as mean ± standard deviation.ResultsCompared with sham rats, there were significant increases in both P2X3 and ASIC3 protein expression in L4‐6 DRGs in IR 18h rats (P2X3: 1.56±0.10 in IR 18h rats/n=4 vs. 1.00±0.10 in sham rats/n=6; P<0.05; and ASIC3: 1.42±0.47 in IR 18h rats/n=8 vs. 1.00±0.07 in sham rats/n=10; P<0.05). In addition, compared with sham rats, the MAP responses following the injection of α‐β‐me‐ATP (0.125 mM) and lactic acid (2 and 4 µmol/kg) were significantly amplified in IR 18h rats (α‐β‐me‐ATP: 29±8 mmHg in IR 18h rats/n=5 vs. 20±5 mmHg in sham rats/n=2; P<0.05; Lactic acid: 2 µmol/kg, 28±8 mmHg in IR 18h rats/n=15 vs. 21±7 mmH in sham rats/n=8, P<0.05; 4 µmol/kg, 37±10 mmHg in IR 18h rats/n=15 vs. 25±6 mmH in sham rats/n=9, P<0.01). In the isolated DRG neurons, amplitude of both P2X and ASIC3 currents was significantly higher in IR 18h rats than that in sham rats. i.e., P2X transient currents: 1281.64±776.74 pA in IR 18h rats/n=25, vs. 717.91±556.2 pA in sham rats/n=9, (P<0.05); and sustain currents: 466.94±168.68 pA in IR 18h rats/n=11, vs. 271.49±200.90 pA in sham rats/n=8 (P<0.05).ConclusionThe activities of the P2X3 and ASIC3 signaling pathways in the muscle afferents are exaggerated following muscle IR. Results of this study shed light upon the future potential intervention strategy to minimize the IR‐induced exaggerated EPR response in the post‐revascularization PAD patients.

Intramuscular insulin administration potentiates sympathetic and pressor responses to capsaicin in rats

Insulin centrally activates the sympathetic nervous system. However, little is known about the effects of insulin on peripheral primary sensory neurons. Transient receptor potential vanilloid 1 (TRPV1), of which capsaicin (CAP) is an agonist, is widely expressed in small dorsal root ganglia (DRG) neurons subserving skeletal muscle thin‐fiber afferents expressing sensory nociceptors and/or metabolically sensitive skeletal muscle receptors. Evidence suggests that insulin increases the sensitivity of these sensory receptors as well as translocation of TRPV1 from cytosol to plasma membrane in DRG neurons. We therefore hypothesized that insulin potentiates the responsiveness of thin fiber muscle afferents to TRPV1 activation.PurposeThe aim of this investigation was 1) to examine whether TRPV1 and insulin receptors (IR) are co‐localized in small‐diameter (< 30 µm) DRG neurons subserving thin‐fiber afferents (C‐fibers or A‐delta fibers), and 2) to determine the effects of insulin on renal sympathetic nerve activity (RSNA) and mean arterial blood pressure (MAP) responses to stimulation of TRPV1 by injection of CAP into the arterial supply of the hindlimb in decerebrated rats.MethodsL4‐L6 DRGs were harvested from Sprague‐Dawley rats (n=3, 19 weeks, body weight: 518 ± 6 g). The percentage of neurons that expressed IR and/or isolectin B4 binding (IB4, a C‐fiber neuronal marker) in TRPV1 positive small DRGs neurons were assessed. RSNA and MAP responses to intra‐arterial administration of CAP (0.3 µg/100 µL) were measured in decerebrate Sprague‐Dawley rats (10 ± 1 weeks, body weight: 330 ± 43 g) before and after intramuscular injection of either insulin (5 U/mL, 30 µL) or saline (vehicle control, 30 µL). To avoid insulin/saline spill over into the systemic circulation, a vascular occluder placed around the abdominal aorta was inflated immediately prior to intramuscular administration of insulin or saline.ResultsImmunohistochemical staining demonstrated that 22 % of TRPV1 positive DRG neurons expressed IR and IB4 binding. Intramuscular insulin administration did not change blood glucose as well as plasma insulin levels assessed from the jugular vein. The RSNA response to CAP after insulin administration was significantly greater than post injection of vehicle (vehicle: 25 ± 24, n=9, vs. insulin: 54 ± 32 %, n=8, P=0.04). While the MAP response to CAP was not significantly changed by vehicle injection (before: 26 ± 13 vs. after: 24 ± 12 mmHg, n=18), insulin administration significantly increased MAP responsiveness (before: 24 ± 1 vs. after: 29 ± 15 mmHg, n=22, P=0.01).ConclusionThe data demonstrate that 1) TRPV1 and IR co‐localize on small DRG neurons and 2) intramuscular insulin administration significantly augments sympathetic and pressor responses to chemical stimulation of skeletal muscle afferents. These findings suggest that insulin potentiates TRPV1 responsiveness at the muscle tissue level, possibly contributing to insulin‐induced sympathoexcitation.

Venoconstrictor responses to activation of bradykinin-sensitive pericardial afferents involve the region of the hypothalamic paraventricular nucleus.

Veins are important in the control of venous return, cardiac output, and cardiovascular homeostasis. However, the effector systems modulating venous function remain to be fully elucidated. We demonstrated that activation of bradykinin‐sensitive pericardial afferents elicited systemic venoconstriction. The hypothalamic paraventricular nucleus (PVN) is an important site modulating autonomic outflow to the venous compartment. We tested the hypothesis that the PVN region is involved in the venoconstrictor response to pericardial injection of bradykinin. Rats were anesthetized with urethane/alpha chloralose and instrumented for recording arterial pressure, vena caval pressure, and mean circulatory filling pressure (MCFP), an index of venous tone. The rats were fitted with a pericardial catheter and PVN injector guide tubes. Mean arterial pressure (MAP), heart rate (HR), and MCFP responses to pericardial injection of bradykinin (1, 10 µg/kg) were recorded before and after PVN injection of omega conotoxin GVIA (200 ng/200 nl). Pericardial injection of saline produced no systematic effects on MAP, HR, or MCFP. In contrast, pericardial injection of bradykinin was associated with short latency increases in MAP (16 ± 4 to 18 ± 2 mm Hg) and MCFP 0.35 ± 0.19 to 1.01 ± 0.27 mm Hg. Heart rate responses to pericardial BK were highly variable, but HR was significantly increased (15 ± 9 bpm) at the higher BK dose. Conotoxin injection in the PVN region did not affect baseline values for these variables. However, injection of conotoxin into the area of the PVN largely attenuated the pressor (−1 ± 3 to 6 ± 3 mm Hg), MCFP (−0.19 ± 0.07 to 0.20 ± 0.18 mm Hg), and HR (4 ± 14 bpm) responses to pericardial bradykinin injection. We conclude that the PVN region is involved in the venoconstrictor responses to pericardial bradykinin injection.

Effectiveness of Angiotensin II for Catecholamine Refractory Septic or Distributive Shock on Mortality: A Propensity Score Weighted Analysis of Real-World Experience in the Medical ICU.

This study examined ATII as a third-line vasopressor based on institutional approval. Retrospective observational cohort study. Medical ICU at an academic tertiary care medical center. Adult patients requiring 3 or more vasopressor agents for septic shock or other forms of distributed shock from September 1, 2018, to January 31, 2020. Effect of ATII after norepinephrine and vasopressin on mortality and mean arterial blood pressure response after 3 hours of administration. One-hundred forty-seven patients, 56 receiving ATII and 91 receiving another vasopressor (non-ATII), were enrolled. Patients in the ATII group had higher mortality compared to the non-ATII group, and more required 5 or greater vasopressor agents (p < 0.01). After propensity score weighting, there remains a trend in higher mortality in the ATII compared to non-ATII group, but not statistically significant (86.0% vs 71.0%, p = 0.16). More patients in the ATII group continued to require 5 or greater vasopressor agents compared to the non-ATII group after propensity score weighting (45.9% vs 12.5%, p < 0.01). SOFA score was the only variable associated with mortality (OR = 1.25, 95% CI, 1.05-1.49; p = 0.01). Patients were considered a "responder" if mean arterial pressure greater than 65 mm Hg at 3 hours after the third vasopressor was initiated. Among the ATII group, 37.5% patients were responders compared to 45.1% responders in the non-ATII group (relative risk = 1.07, 95% CI, 0.6-1.93; p = 0.81). Although previous data support the use of ATII due to its favorable hemodynamic response in patients with distributive shock, there was no observed benefit in mortality or hemodynamic response with ATII as a third-line vasopressor in our study of real-world patients.

Handgrip exercise induces sex-specific mean arterial pressure and oxygenation responses but similar performance fatigability.

Women exhibit an attenuated exercise pressor reflex (EPR) when compared to men. The influence of sex-specific mechanisms related to the EPR and performance fatigability remain to be fully elucidated. The purpose was to determine the impact of oxygenation and metabolic efficiency on sex-specific performance fatigability and increases in mean arterial pressure (MAP) resulting from a fatiguing isometric handgrip (IHG). Twenty-four adults volunteered to perform an IHG at 25% at maximal voluntary isometric contractions (MVICs). Pre- and posttest MVICs were conducted to quantify performance fatigability. MAP was collected at 3 timepoints. A near-infrared spectroscopy device was attached to the forearm to derive the following signals: oxy[haem], deoxy[haem], total[haem], and diff[haem]. These values were normalized and examined across time in 5% segments of time-to-task-failure. Metabolic efficiency was defined as the ratio force:deoxy[haem]. During the IHG, there was a decline in oxy[haem] for the men (b = -0.075), whereas the women demonstrated an increase (b = 0.117). For the men, the diff[haem] tracked the mean oxy[haem] response, but there was no change for the women. The men exhibited greater declines in metabolic efficiency, yet there were no sex differences in PF (46.6 ± 9.7% vs. 45.5 ± 14.2%). For relative MAP, the men (24.5 ± 15.1%) exhibited a greater (p = .03) increase than the women (11.0 ± 17.6%). These results indicated the EPR was more prominent for the men, perhaps due to differences in mechanical stimuli and a lack of ability to maintain metabolic efficiency. However, these physiological differences did not induce a sex difference in performance fatigability.

Sustained hypoxia in mice increases parasympathetic but not sympathetic tone.

The autonomic profile of mice submitted to sustained hypoxia (SH) was not yet fully evaluated. Herein, we characterized the cardiovascular and autonomic profile of conscious freely moving mice submitted to SH using two sequential experimental protocols to evaluate the parasympathetic and sympathetic tone to the heart and the sympathetic tone to the vascular resistance. In the first protocol the sequence of antagonists was methyl-atropine followed by propranolol and then by prazosin, while in the second protocol the sequence was propranolol followed by methyl-atropine and then by prazosin. In SH the baseline heart rate was significantly lower than in control mice and the antagonism of the parasympathetic and sympathetic tone to the heart in both experimental protocols indicated an increased parasympathetic tone in SH mice and no changes in the sympathetic tone. Antagonism of the sympathetic tone to the vascular resistance with prazosin produced similar changes in arterial pressure in control and SH mice. Altogether these findings support the concept that mice submitted to SH present a significant increase in the parasympathetic but not in the sympathetic tone, which may explain why the baseline arterial pressure was not increased in SH mice.

Hemodynamic patterns associated with activation of bradykinin-sensitive pericardial afferents.

The heart is endowed with reflexogenic areas capable of powerful blood pressure responses. Relatively little work has studied the hemodynamic mechanisms underlying these responses and whether these are sexually dimorphic. We hypothesized that activation of bradykinin-sensitive pericardial afferents would produce a sexually dimorphic cardiac output response. Male and female Sprague Dawley rats were anesthetized and instrumented with catheters for recording arterial pressure, with an aortic arch flow probe to record cardiac output and with a catheter in the pericardial sac. Mean arterial pressure (MAP), cardiac index (CI) and total peripheral resistance index (TPRI) responses to pericardial bradykinin injection (0.1, 1 μg/kg) were recorded. Pericardial bradykinin injection caused similar increases in MAP in male and female rats. However, the underlying hemodynamic patterns varied considerably. We identified a cluster of CI responders and TPRI responders in both male and female rats. Within CI responders, females exhibited greater CI increases than males. Conversely, in TPRI responders, males exhibited a greater TPRI increase than females. We conclude that aggregate activation of bradykinin-sensitive pericardial afferents is associated with a relatively uniform pressor response but different hemodynamic patterns with males exhibiting a more robust vascular response and females a more robust cardiac output response.

Associations of corin genetic polymorphisms with salt sensitivity, blood pressure changes, and hypertension incidence in Chinese adults.

Corin, a transmembrane serine protease that can cleave pro‐atrial natriuretic peptide (Pro‐ANP) into smaller bioactive molecule atrial natriuretic peptide, has been shown to be involved in the pathophysiology of hypertension, cardiac hypertrophy. We sought to examine the associations of corin genetic variations with salt sensitivity, blood pressure (BP) changes and hypertension incidence. We studied participants of the original Baoji Salt‐Sensitive cohort, recruited from 124 families from seven Chinese villages in 2004 who sequentially received a usual baseline salt diet, a 7‐day low salt diet (3 g/day) and a 7‐day high salt diet (18 g/day), respectively. They were followed up for 8 years (in 2009, 2012) to evaluate the development of hypertension. Corin SNP rs3749584 was significantly associated with diastolic BP (DBP) and mean arterial pressure (MAP) response to low‐salt diet, while rs4695253, rs17654278 were associated with pulse pressure (PP) response to low‐salt diet. SNPs rs4695253, rs12509275, rs2351783, rs2271036, rs2271037 were significantly associated with systolic BP (SBP), DBP, and MAP responses to high‐salt diet. In addition, SNPs rs12641823, rs6834933, rs2271036, and rs22710367 were significantly associated with the longitudinal changes in SBP, DBP, MAP, or PP over 8 years of follow‐up. SNP rs73814824 was significantly associated with the incidence of hypertension over 8 years. Gene‐based analysis showed that corin gene was significantly associated with longitudinal BP changes and hypertension incidence after 8‐year follow‐up. This study suggests that corin may play a role in salt sensitivity, BP progression, and development of hypertension.

Abstract 10234: Exaggerated Blood Pressure Response to Static Exercise Following Muscle Ischemia-Reperfusion: A Time-Course Investigation

Background: Peripheral artery disease (PAD) is one of the major cardiovascular concerns and dramatically reduces the blood flow supply in the affected limbs. A combination of revascularization surgery in the femoral artery and supervised exercise intervention is among the most general approaches for the treatment of PAD. However, the effects of ischemia-reperfusion (IR), which is one of the most predominant complications resulting from the revascularization surgery, on exercise-induced arterial blood pressure (BP) response are poorly understood. Methods: We examined the BP response to static muscle contraction in rats at different time points after the IR procedure. Four groups were included: 1. Sham rats; 2. Rats with 18 hours following IR (IR 18h); 3. Rats with 66 hours following IR (IR 66h); 4. Rats with 114 hours following IR (IR 114h). One-way ANOVA with LSD post-hoc test was applied to analyze the difference among groups. Data were presented as Mean ± Standard Deviation. Results: Compared with Sham group, the BP response to static muscle contraction was significantly increased in rats with all the investigated time points. The response of mean arterial pressure was 19±3 mmHg in Sham rats (n=6); 29±9 mmHg in IR 18h rats (n=8); 26±7 mmHg in IR 66h rats (n=10); 26±4 mmHg in IR 114h rats (n=9) ( P &lt;0.05; the groups at three time courses vs. Sham). There was no significant difference observed in the peak developed tension during muscle contraction among all the groups (Sham rats: 543±101g; IR 18h rats: 520±28g; IR 66h rats: 554±66g; IR 114h rats: 562±45g; P &gt;0.05). Conclusions: IR significantly exaggerates the static exercise-induced BP response. Whereas the BP response tends to decrease with the prolonged IR time, the exaggerated BP response remains through time points from post IR 18 hours to 114 hours. The data suggest that a chronic time course should be considered to alleviate IR-induced ischemic injury in PAD patients for clinical interventions appropriated and exercise.

Abstract 9053: ASIC3 Knockout Alleviates Exaggerated Blood Pressure Response Induced by P2X3 Activation in Hindlimb Muscle Afferent Nerves of Rats With Experimental Peripheral Artery Disease

Background: In peripheral artery disease (PAD), the metaboreceptor and mechanoreceptor in muscle afferent nerves contribute to accentuated sympathetic outflow via a neural reflex. Particularly, lactic acid and ATP produced in exercising muscles respectively stimulate acid sensing ion channel subtype 3 (ASIC3) and purinergic subunit P2X3 receptors in muscle afferent nerves, inducing the reflex sympathetic and arterial blood pressure responses during exercise. Methods: We examined that the P2X3 protein expression in the dorsal root ganglion (DRG) and P2X currents in DRG neurons using western blotting and patch-clamp methods, and the pressor response to P2X3 stimulation using the whole animal preparations. Four groups were included: 1. Wild type (WT) rats; 2. ASIC3 knockout (KO) rats; 3. WT-PAD rats with three days of femoral artery occlusion; 4. KO-PAD rats with three days of femoral artery occlusion. Results: First, P2X3 expression was significantly increased in KO rats compared with that in WT rats (optical density: 6.51±2.20/n=5; P &lt;0.05 vs. WT). However, the levels of P2X3 expression were not significantly increased in KO-PAD rats compared with the KO rats (optical density: 7.99±1.99/n=6; P &gt;0.05 vs. KO) . Second, in WT rats, as 10, 30 and 50 μM of αβ-me ATP (P2X3 agonist) were applied, peak amplitude of both transient and sustained P2X currents was increased by femoral artery occlusion (all P &lt;0.05 WT-PAD vs. WT). Insignificant differences in both transient and sustained P2X currents were found between KO rats and KO-PAD rats (all P &gt;0.05 vs. KO) when αβ-me ATP was applied except of the transient P2X current amplitude at 50 μM of αβ-me ATP. Third, there were insignificant differences in the mean arterial pressure response to 0.0625, 0.125 and 0.25 mM of αβ-me ATP injected into the hindlimb circulation between KO rats and KO-PAD rats (all P &gt;0.05 vs. KO). Conclusions: Compared with WT rats, augmented P2X3-mediated pressor response is blunted by ASIC3 KO in PAD rats and this is accompanied with downregulated P2X3 expression and suppressed activities in P2X3 signaling pathways in muscle afferent neurons.

Acute hyperoxia reveals tonic influence of peripheral chemoreceptors on systemic vascular resistance in heart failure patients

Peripheral chemoreceptors’ (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.

Sequential measurement of the neurosensory retina in hypertensive disorders of pregnancy: a model of microvascular injury in hypertensive emergency

Optical coherence tomography of the eye suggests the retina thins in normal pregnancy. Our objectives were to confirm and extend these observations to women with hypertensive disorders of pregnancy (HDP). Maternal demographics, clinical/laboratory findings and measurements of macular thickness were repeatedly collected at gestational ages <20 weeks, 20-weeks to delivery, at delivery and postpartum. The primary outcome was the change in macular thickness from non-pregnant dimensions in women with incident HDP compared to non-hypertensive pregnant controls. Secondary outcomes were the relationship(s) between mean arterial pressure (MAP) and macular response. Data show macular thicknesses diminished at <20 weeks gestation in each of 27 pregnancies ending in HDP (mean 3.94 µm; 95% CI 4.66, 3.21) and 11 controls (mean 3.92 µm; 5.05, 2.79; P < 0.001 versus non-pregnant dimensions in both; P = 0.983 HDP versus controls). This thinning response continued to delivery in all controls and in 7 women with HDP superimposed on chronic hypertension. Macular thinning was lost after 20 weeks gestation in the other 20 women with HDP. MAP at loss of macular thinning in women without prior hypertension (n = 12) was identical to MAP at enrollment. However, mean MAP subsequently rose 19 mmHg (15, 22) leading to de novo HDP in all 12 women. Loss of thinning leading to a rise in MAP was also observed in 8 of 15 women with HDP superimposed on chronic hypertension. We conclude the macula thins in most women in early pregnancy. Those who lose this early macular thinning response often develop blood pressure elevations leading to HDP.

Neck Chamber Technique Revisited: Low-Noise Device Delivering Negative and Positive Pressure and Enabling Concomitant Carotid Artery Imaging With Ultrasonography.

Background and Objectives: Recently, novel noiseless device for the assessment of baroreceptor function with the neck suction (NS) has been presented. In this study, we present another in-house approach to the variable-pressure neck chamber method. Our device offers further critical improvements. First, it enables delivery of negative (NS) as well as positive pressure (neck pressurizing, NP) in a noiseless manner. Second, we used small, 3D-printed cups positioned over the carotid sinuses instead of cumbersome neck collar to improve subject comfort and to test feasibility of tracking the pressure-induced changes in carotid artery with ultrasonography.Methods: Five healthy, non-smoking, normal-weight subjects aged 29 ± 3 years (mean ± SD) volunteered for the study. Heart rate (HR, bpm) and mean arterial pressure (MAP, mmHg) responses to short, 7-s long episodes of NS and NP were recorded. Each trial consisted of 12 episodes of variable-pressure: six episodes of NS (suction ranging between -10 and -80 mmHg) and six episodes of NP (pressure ranging between + 10 and + 80 mmHg). Carotid artery sonography was performed during the NS and NP in four subjects, on another occasion.Results: The variable-pressure episodes resulted consistently in the expected pattern of hemodynamic alterations: HR and MAP increases or decreases following the NP and NS, respectively, as evidenced by the coefficient of determination (R2) of ≥0.78 for the carotid-HR response curve (for all five participants) and the carotid-MAP response curve (for four out of five participants; the curve cannot be calculated for one subject). We found a linear, dose-dependent relation between the applied pressure and the systolic-diastolic difference in carotid artery diameter.Conclusion: The novel device enables noiseless stimulation and unloading of the carotid baroreceptors with the negative and positive pressure, respectively, applied on the subject’s neck via small, asymmetric and one-side flattened, 3D-printed cups. The unique design of the cups enables concomitant visualizing of the carotid artery during the NS or NP administration, and thereby direct monitoring of the intensity of mechanical stimulus targeting the carotid baroreceptors.

Vagus nerve bundle stimulation using 1505-nm laser irradiation in an in-vivo rat model.

Laser nerve stimulation using near-infrared laser irradiation has recently been studied in the peripheral nervous system as an alternative method to conventional electrical nerve stimulation. Bringing this method to the vagus nerve model could leverage this emerging stimulation approach to be tested in broader preclinical applications. Here, we report the capability of the laser nerve stimulation method on the rat vagus nerve bundle with a 1505-nm diode laser operated in continuous-wave mode. Studies of the stimulation threshold and laser-induced acute thermal injury to the nerve bundle were also performed to determine a temperature window for safe, reliable and reproducible laser stimulation of the rat vagus nerve bundle. The results show that laser stimulation of the vagus nerve bundle provides reliable and reproducible nerve stimulation in a rat model. These results also confirm a threshold temperature of >42°C with acute nerve damage observed above 46°C. A strong correlation was obtained between the laser time required to raise the nerve temperature above the stimulation threshold and the mean arterial pressure response. Advantages of the method such as non-contact delivery of external stimulus signals at mm scaled distance in air, enhanced spatial selectivity and electrical artefact-free measurements may indicate its potential to counteract the side effects of conventional electrical vagus nerve stimulation.

Rapid 500 mL albumin bolus versus rapid 200 mL bolus followed by slower continuous infusion in post-cardiac surgery patients: a pilot before-and-after study

Objective: To evaluate the haemodynamic effects of rapid fluid bolus therapy (FBT) (500 mL of 4% albumin over several minutes) versus combined FBT (rapid 200 mL FBT followed by a 300 mL infusion over 30 minutes).Design: Single centre, prospective, before-and-after trial.Setting: A tertiary intensive care unit in Australia.Participants: Fifty mechanically ventilated post-cardiac surgery patients.Interventions: Rapid 4% albumin FBT versus combined FBT.Main outcome measures: We recorded haemodynamic parameters from before FBT to 30 minutes after FBT. A mean arterial pressure (MAP) response was defined by a MAP increase > 10%, and a cardiac index (CI) response was defined by a CI increase > 15%.Results: Immediately after rapid FBT versus combined FBT, there was a CI response in 13 patients (52%) compared with five patients (20%) respectively (P = 0.038), and a MAP response in 11 patients (44%) in each group. However, from FBT administration to 30 minutes, there was a time and group interaction such that MAP was higher in the rapid FBT group (P = 0.003), as was the case for central venous pressure (P = 0.002) and mean pulmonary artery pressure (P < 0.001). Body temperature fell immediately and was lower with rapid FBT but became warmer than with combined FBT later (P < 0.001). At 30 minutes, a MAP response was seen in ten patients (40%) compared with nine patients (36%) (P < 0.99) and a CI response was present in eight patients (32%) compared with 11 patients (44%) (P = 0.56) in the rapid versus combined FBT groups respectively.Conclusion: Rapid FBT was superior to combined FBT in terms of mean MAP levels and immediate CI response. However, the number of MAP responders or CI responders was similar at 30 minutes.

A method to quantify autonomic nervous system function in healthy, able-bodied individuals

BackgroundThe autonomic nervous system (ANS) maintains physiological homeostasis in various organ systems via parasympathetic and sympathetic branches. ANS function is altered in common diffuse and focal conditions and heralds the beginning of environmental and disease stresses. Reliable, sensitive, and quantitative biomarkers, first defined in healthy participants, could discriminate among clinically useful changes in ANS function. This framework combines controlled autonomic testing with feature extraction during physiological responses.MethodsTwenty-one individuals were assessed in two morning and two afternoon sessions over two weeks. Each session included five standard clinical tests probing autonomic function: squat test, cold pressor test, diving reflex test, deep breathing, and Valsalva maneuver. Noninvasive sensors captured continuous electrocardiography, blood pressure, breathing, electrodermal activity, and pupil diameter. Heart rate, heart rate variability, mean arterial pressure, electrodermal activity, and pupil diameter responses to the perturbations were extracted, and averages across participants were computed. A template matching algorithm calculated scaling and stretching features that optimally fit the average to an individual response. These features were grouped based on test and modality to derive sympathetic and parasympathetic indices for this healthy population.ResultsA significant positive correlation (p = 0.000377) was found between sympathetic amplitude response and body mass index. Additionally, longer duration and larger amplitude sympathetic and longer duration parasympathetic responses occurred in afternoon testing sessions; larger amplitude parasympathetic responses occurred in morning sessions.ConclusionsThese results demonstrate the robustness and sensitivity of an algorithmic approach to extract multimodal responses from standard tests. This novel method of quantifying ANS function can be used for early diagnosis, measurement of disease progression, or treatment evaluation.Trial registrationThis study registered with Clinicaltrials.gov, identifier NCT04100486. Registered September 24, 2019, https://www.clinicaltrials.gov/ct2/show/NCT04100486.

Associations of plasma uromodulin and genetic variants with blood pressure responses to dietary salt interventions.

Uromodulin, also named Tamm Horsfall protein, have been associated with renal function and sodium homeostasis regulation. The authors sought to examine the effects of salt intake on plasma and urinary uromodulin levels and the association of its genetic variants with salt sensitivity in Chinese adults. Eighty patients from our natural population cohort were maintained sequentially either on a usual diet for 3 days, a low‐salt diet (3.0 g) for 7 days, and a high‐salt diet (18.0 g) for an additional 7 days. In addition, the authors studied 514 patients of the Baoji Salt‐Sensitive Study, recruited from 124 families who received the same salt intake intervention, and investigated the association of genetic variations in uromodulin gene with salt sensitivity. Plasma uromodulin levels were significantly lower on a high‐salt diet than on a baseline diet (28.3 ± 4.5 vs. 54.9 ± 8.8 ng/ml). Daily urinary excretions of uromodulin were significantly decreased on a high‐salt diet than on a low‐salt diet (28.7 ± 6.7 vs. 157.2 ± 21.7 ng/ml). SNPs rs7193058 and rs4997081 were associated with the diastolic blood pressure (DBP), mean arterial pressure (MAP) responses to the high‐salt diet. In addition, several SNPs in the uromodulin gene were significantly associated with pulse pressure (PP) response to the low‐salt intervention. This study shows that dietary salt intake affects plasma and urinary uromodulin levels and that uromodulin may play a role in the pathophysiological process of salt sensitivity in the Chinese populations.

Chronic ablation of TRPV1-sensitive skeletal muscle afferents attenuates the muscle metaboreflex.

Exercise intolerance is a hallmark symptom of cardiovascular disease and likely occurs via enhanced activation of muscle metaboreflex-induced vasoconstriction of the heart and active skeletal muscle which, thereby limits cardiac output and peripheral blood flow. Muscle metaboreflex vasoconstrictor responses occur via activation of metabolite-sensitive afferent fibers located in ischemic active skeletal muscle, some of which express transient receptor potential vanilloid 1 (TRPV1) cation channels. Local cardiac and intrathecal administration of an ultrapotent noncompetitive, dominant negative agonist resiniferatoxin (RTX) can ablate these TRPV1-sensitive afferents. This technique has been used to attenuate cardiac sympathetic afferents and nociceptive pain. We investigated whether intrathecal administration (L4-L6) of RTX (2 µg/kg) could chronically attenuate subsequent muscle metaboreflex responses elicited by reductions in hindlimb blood flow during mild exercise (3.2 km/h) in chronically instrumented conscious canines. RTX significantly attenuated metaboreflex-induced increases in mean arterial pressure (27 ± 5.0 mmHg vs. 6 ± 8.2 mmHg), cardiac output (1.40 ± 0.2 L/min vs. 0.28 ± 0.1 L/min), and stroke work (2.27 ± 0.2 L·mmHg vs. 1.01 ± 0.2 L·mmHg). Effects were maintained until 78 ± 14 days post-RTX at which point the efficacy of RTX injection was tested by intra-arterial administration of capsaicin (20 µg/kg). A significant reduction in the mean arterial pressure response (+45.7 ± 6.5 mmHg pre-RTX vs. +19.7 ± 3.1 mmHg post-RTX) was observed. We conclude that intrathecal administration of RTX can chronically attenuate the muscle metaboreflex and could potentially alleviate enhanced sympatho-activation observed in cardiovascular disease states.

Characteristics and Physiologic Changes After 4% Albumin Fluid Boluses in a PICU.

To describe the characteristics, hemodynamic, and physiologic changes after 4% albumin fluid boluses in critically ill children. Retrospective observational study. Single-center PICU. Children in a cardiac and general PICU. None. Between January 2017 and May 2019, there were 1,003 fluid boluses of 4% albumin during 420 of 5,731 admissions (7.8%), most commonly in children with congenital/acquired heart disease (71.2%) and sepsis (7.9%). The median fluid bolus dose was 10 mL/kg (interquartile range, 5.8-14.6 mL/kg), and its duration 30 minutes (interquartile range, 14.0-40.0 min; n = 223). After the fluid bolus, a significant change in mean arterial pressure (2.3 mm Hg [5.1%], 2.7 mm Hg [5.8%], 2.9 mm Hg [6.1%], and 3.8 mm Hg [8.0%] at 1, 2, 3, and 4 hr, respectively [p ≤ 0.001]) only occurred in children less than or equal to 12 months old. A mean arterial pressure response, defined by an increase greater than or equal to 10% from baseline, occurred in 290 of 887 patients (33%) with maximal response at 1 hour. Hypotension at baseline predicted the magnitude of mean arterial pressure increase at 60 (coefficient 24.3 [95% CI, 0.79-7.87]; p = 0.04) and 120 minutes (coefficient 26.1 [95% CI, 2.75-48.2]; p = 0.02). There were no biochemical or hematocrit changes within 4 hours of the fluid bolus. Urine output for the entire cohort was 2 mL/kg/hr at baseline and did not change with the fluid bolus. Fluid boluses of 4% albumin were common and predominantly in children with cardiac disease and sepsis with a median dose of 10 mL/kg given over half an hour. Such treatment was associated with significant hemodynamic changes only in children less than 12 months old, and we failed to identify an association with urine output.