Changes In Vascular Resistance Research Articles

Percutaneous transluminal pulmonary angioplasty for Takayasu arteritis-associated pulmonary hypertension: A single-arm meta-analysis.

The efficacy and safety of percutaneous transluminal pulmonary angioplasty (PTPA) for Takayasu arteritis-associated pulmonary hypertension (TA-PH) remain unclear. To examine the efficacy and safety of PTPA in TA-PH. PubMed, Embase, and the Cochrane Central Register of Controlled Trials Library were searched from inception to August 18, 2022, for articles investigating the efficacy and safety of PTPA for TA-PH. The primary efficacy outcomes were pulmonary vascular resistance (PVR) changes from baseline to re-evaluation and 6-minute walking distance (6MWD). The safety outcome was procedure-related complications. Five articles comprising 104 patients with TA-PH who underwent PTPA were included. The scores of article quality, as assessed using the methodological index for nonrandomized studies tool, were high, ranging from 13 to 15 points. The pooled treatment effects of PVR (weighted mean difference [WMD]: -4.8 WU; 95% confidence interval [CI]: -6.0 to -3.5 WU; I2 = 0.0%), 6MWD (WMD: 101.9 m; 95% CI: 60.3-143.6 m; I2 = 70.4%) significantly improved. Procedure-related complications, which predominantly present as pulmonary artery injury and pulmonary injury, occurred in 32.0% of the included patients. Periprocedural death occurred in one patient (1.0%, 1/100). Patients with TA-PH could benefit from PTPA in terms of hemodynamics and exercise tolerance, at the expense of procedure-related complications. PTPA should be encouraged to enhance the treatment response in TA-PH. These findings need to be confirmed by further studies, ideally, randomized controlled trials. PROSPERO CRD42022354087.

A Novel Dual Energy Computed Tomography Score Correlates With Postoperative Outcomes in Chronic Thromboembolic Pulmonary Hypertension.

To compare dual-energy computed tomography (DECT) based qualitative and quantitative parameters in chronic thromboembolic pulmonary hypertension with various postoperative primary and secondary endpoints. This was a retrospective analysis of 64 patients with chronic thromboembolic pulmonary hypertension who underwent DECT. First, a clot score was calculated by assigning the following score: pulmonary trunk-5, each main pulmonary artery-4, each lobar-3, each segmental-2, and subsegmental-1 per lobe; the sum total was then calculated. The perfusion defect (PD) score was calculated by assigning 1 point to each segmental PD. The combined score was calculated by adding clot and PD scores. For quantitative evaluation, we calculated perfused blood volume (PBV) (%) of each lung and the sum of both lungs. Primary endpoints included testing association between combined score and total PBV with change in mean pulmonary arterial pressure ([mPAP], change calculated as preop minus postop values). Secondary endpoints included explorative analysis of the correlation between combined score and PBV with change in preoperative and postoperative pulmonary vascular resistance, change in preoperative 6-minute walk distance (6MWD), and immediate postoperative complications such as reperfusion edema, ECMO placement, stroke, death and mechanical ventilation for more than 48 hours, all within 1 month of surgery. Higher combined scores were associated with larger decreases in mPAP ( =0.27, P =0.036). On average, the decrease in mPAP (pre mPAP-post mPAP) increased by 2.2mmHg (95% CI: -0.6, 5.0) with each 10 unit increase in combined score. The correlation between total PBV and change in mPAP was small and not statistically significant. During an exploratory analysis, higher combined scores were associated with larger increases in 6MWD at 6 months postprocedure ( =0.55, P =0.002). Calculation of DECT-based combined score offers potential in the evaluation of hemodynamic response to surgery. This response can also be objectively quantified.

Animal experimental study on the effects of different levels of amputation on cardiovascular system

Vascular injury resulting from lower limb amputation leads to the redistribution of blood flow and changes in vascular terminal resistance, which can affect the cardiovascular system. However, there was no clear understanding of how different amputation levels affect the cardiovascular system in animal experiments. Therefore, this study established two animal models of above-knee amputation (AKA) and below-knee amputation (BKA) to explore the effects of different amputation levels on the cardiovascular system through blood and histopathological examinations. The results showed that amputation caused pathological changes in the cardiovascular system of animals, including endothelial injury, inflammation, and angiosclerosis. The degree of cardiovascular injury was higher in the AKA group than in the BKA group. This study sheds light on the internal mechanisms of amputation's impact on the cardiovascular system. Based on the amputation level of patients, the findings recommend more comprehensive and targeted monitoring after surgery and necessary interventions to prevent cardiovascular diseases.

Hemodynamic effects of a low versus a high dose of propofol during induction of anesthesia. A randomized trial.

Hypotension is common after anesthesia induction with propofol and is associated with increased morbidity. It is important to examine the effects of the proposed interventions to limit preventable hypotension, as suggested by the reduction in the dose of propofol. Our objective was to investigate whether a high dose of propofol is inferior to a low dose with respect to changes in systolic arterial blood pressure (SAP). This randomized, double-blind, dose-controlled, non-inferiority study included 68 healthy women scheduled for gynecological surgery at the Day Surgery Unit, Haugesund Hospital, Norway. The patients were randomly allocated 1:1 to a low or high dose (1.4 mg/kg total body weight (TBW) versus 2.7 mg/kg TBW of propofol corresponding to maximal effect site concentrations (Ce) of 2.0 μg/mL versus 4.0 μg/mL. The dose of remifentanil was 1.9-2.0 μg/kg TBW, with maximal Ce of 5.0 ng/mL. The patients were observed for 450 s from the start of the infusions. The first 150 s was the sedation period, after which a bolus of propofol and remifentanil was administered. Baseline was defined as 55-5 s before the bolus doses. LiDCOplus was used for invasive beat-to-beat hemodynamic monitoring of changes in SAP, heart rate (HR), cardiac output (CO), stroke volume (SV), and systemic vascular resistance (SVR). A difference of 10 mmHg in the change in SAP was considered to be clinically important. The SAP change difference for low versus high dose was -2.9 mmHg (95% CI -9.0-3.1). The relative changes for low versus high dose were SAP -31% versus -36%, (p < .01); HR -24% versus -20%, (p = .09); SVR -20% versus -31%, (p < .001); SV -16% versus -20%, (p = .04); and CO -35% versus -32%, (p = .33). A high dose of propofol was not inferior to a low dose, and a reduction in the dose of propofol did not result in clinically important attenuation of major hemodynamic changes during induction in healthy women. ClinicalTrials.gov identifier NCT03861364, January 3, 2019.

P98: Hemodynamic Effects of Minimally Invasive Mechanical Circulatory Support – Impella 5.5 versus Intra-Aortic Balloon Pump

Background: While the hemodynamic benefits of durable LVADs and intra-aortic balloon pumps (IABPs) in patients with acute-on-chronic heart failure are well described, the hemodynamic effects of the minimally-invasive Impella 5.5 in this patient population are not. Methods: Patient and hemodynamic data on all Impella 5.5 and IABP recipients between August 2020-November 2022 were extracted from a single-institutional database. Only patients with a history of decompensated chronic congestive heart failure were included. Patients requiring Impella support after myocardial infarction or immediately after cardiac surgery were excluded. The primary outcome was survival at 30 days after implantation. Secondary outcomes included changes in pulmonary vascular resistance (PVR), pulmonary capillary wedge pressure (PCWP), and cardiac index (CI) between device implantation and removal. Results: We identified 25 Impella 5.5 patients (12.0% female), 68 IABP patients (19.1% female), and 21 patients who had IABP exchanged for Impella 5.5 (14.2% female). There were no significant differences in baseline characteristics or hemodynamics between Impella 5.5 and isolated IABP patients (Table). Median support duration was significantly longer in the Impella 5.5 cohort (11 days vs. 8 days, p = 0.04). There was no significant difference in survival at 30 days between groups (Figure). PVR and PCWP significantly decreased in both cohorts, while CI significantly increased (Table). The percent increase in CI was significantly greater in Impella 5.5 patients than in IABP patients (67.8% vs 33.6%, p=0.01). However, only the IABP cohort demonstrated significantly decreased mean pulmonary artery pressure (PAP) (-7.0 mmHg, p<0.01) and central venous pressure (CVP) (-3.5 mmHg, p=0.03). Exchanging IABP to Impella 5.5 significantly improved PVR (-50.92 dynes sec cm-5, p=0.03), but not other hemodynamic parameters. Conclusion: Both IABP and Impella 5.5 improve hemodynamics by decreasing pulmonary congestion and increasing cardiac output. While only the IABP significantly decreased mean PAP and CVP, the Impella 5.5 provided greater improvements in CI, and exchanging IABP for Impella 5.5 provided further reductions in PVR.Figure 1. 30-day survival after Impella 5.5 or IABP. - IABP (n=68) Impella 5.5 (n=25) P-value Age 59.10 (47.12-64.97) 44.58 (40.3-63.2) 0.1824 Female 19.1% (13/68) 12.0% (3/25) 0.5442 ICM 30.9% (21/68) 40.3% (10/25) 0.4585 Pre-op PVR 240.0 (176.0-344.0) 231.0 (191.8-344.0) 0.4294 Pre-op PCWP 30.0 (26.0-34.0) 27.0 (20.5-34.0) 0.1186 Pre-op mean PAP 41.5 (37.8-48.0) 40.0 (32.5-49.3) 0.1964 Pre-op CVP 14.0 (10.0-12.5) 14.0 (10.0-22.0) 0.3746 Pre-op CO 3.6 (3.0-4.4) 3.6 (3.0-4.6) 0.3184 Pre-op CI 1.7 (1.5-2.1) 1.9 (1.5-2.2) 0.3184 IABP => Impella 5.5 Pre-exchange Pre-explant P-value PVR 184.4 (111.9-253.1) 148.2 (94.45-214.2) 0.0290 PCWP 23.0 (18.8-27.8) 22.0 (16.0-31.0) 0.3398 Mean PAP 34.5 (29.0-38.3) 35.0 (32.0-38.0) 0.2142 CVP 12.0 (7.50-20.5) 13.0 (9.8-18.8) 0.4431 CO 4.3 (3.3-5.4) 4.9 (4.0-6.1) 0.1832 CI 2.1 (1.6-2.8) 2.3 (2.1-2.6) 0.1526

Differential frequency-dependent reflex summation of the aortic baroreceptor afferent input.

Reflex summation in the expression of left and right aortic baroreflex control of hemodynamic functions was investigated. In anesthetized Sprague-Dawley rats, mean arterial pressure (MAP), heart rate (HR), and mesenteric vascular resistance (MVR) were recorded following left, right, and bilateral stimulation of the aortic depressor nerve (ADN). Stimulation frequency was varied between low (1Hz), moderate (5Hz), and high (20Hz). At 1Hz, left and right ADN stimulation evoked similar depressor, bradycardic and MVR responses, whereas bilateral stimulation induced larger MAP, HR, and MVR reductions compared with stimulations of either side. The sum of the separate and combined stimulation effects on MAP, HR, and MVR was similar, indicating an additive summation. A similar additive summation was observed with HR responses at 5 and 20Hz. Left-sided and bilateral stimulation produced greater depressor and MVR responses than right-sided stimulation, with responses of the bilateral stimulation mimicking those of the left side. The bilateral MAP or MVR response was smaller than the sum of the separate responses, suggesting an inhibitory summation. In conclusion, reflex summation of the left and right aortic baroreceptor afferent input is differentially expressed in relation to the frequency of the input signal. Summation of baroreflex control of HR is always additive and independent of stimulation frequency. Summation of baroreflex control of MAP is additive when the frequency input is small and inhibitory when the frequency input is moderate to high, with MAP changes mainly driven by parallel baroreflex-triggered changes in vascular resistance.

Relaxin mechanistic effects on renal hemodynamics and natriuresis: a mathematical modeling approach

Relaxin (RLX) is a hormone that stimulates renal vasodilation during early pregnancy. Recombinant RLX may have potential as a treatment for heart failure and chronic kidney disease, but its application has been limited in part due to uncertainties about its mechanism of action, and particularly its effect on glomerular capillary hydrostatic pressure (P gc ) and fluid status. The objective of this study was to couple mathematical modeling with experimental observations of the renal hemodynamic and natriuretic response to RLX, in order to quantitatively describe the mechanistic effects of relaxin on the kidney, and to predict its effect on clinically difficult-to-measure variables such as P gc . Utilizing a previously developed mathematical model of kidney function and hemodynamics, we began by hypothesizing a minimum set of RLX mechanisms (afferent/efferent vasodilation), fitting the available hemodynamic/natriuretic response in two previously published rat studies (GFR, renal plasma flow (RPF), mean arterial pressure (MAP), sodium and water excretion), and adding additional RLX mechanisms to the model only when the minimal set could not explain available data. We found that changes in renal vascular resistances alone were sufficient to reproduce observed changes in RPF, but insufficient to explain other data features. Experimental studies reported much larger increases in sodium excretion relative to water excretion with RLX, and this effect could only be reproduced if an effect of RLX on the osmotic setpoint for vasopressin release was included in the model – a mechanism that has previously been reported in ovariectomized rats treated with RLX. A small effect of RLX on heart rate was necessary to produce observed changes in MAP.In addition, the single experimental study in which P gc has been measured with RLX reported a rise in GFR but fall in P gc , and this difference could not be explained mathematically by relative afferent/efferent dilation or by downstream shifting of the filtration equilibrium with increased RPF; it could only be reproduced mathematically if RLX was assumed to large positive effect on glomerular membrane permeability. However, the magnitude of this effect is difficult to justify physiologically. Thus, while the model can be forced to fit this limited data, further study is needed to understand whether and how RLX might have such large permeability effects.The fitted model was then able to make predictions consistent with observed renal responses in human subjects, and these effects were better predicted when the RLX effect on permeability was excluded, further suggesting that this effect may not be real. In these simulations, RLX had no net effect on P gc . In conclusion, while some uncertainty remains, this analysis suggests that RLX acts primarily by dilating the afferent and efferent arterioles and shifting the osmotic setpoint for vasopressin release. AstraZeneca and Eli Lilly This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Elastin haploinsufficiency accelerates age-related structural and functional changes in the renal microvasculature and impairment of renal hemodynamics in female mice.

Age-related decline in functional elastin is associated with increased arterial stiffness, a known risk factor for developing cardiovascular disease. While the contribution of elastin insufficiency to the stiffening of conduit arteries is well described, little is known about the impact on the structure and function of the resistance vasculature, which contributes to total peripheral resistance and the regulation of organ perfusion. In this study, we determined how elastin insufficiency impinges on age-related changes in the structure and biomechanical properties of the renal microvasculature, altering renal hemodynamics and the response of the renal vascular bed to changes in renal perfusion pressure (RPP) in female mice. Using Doppler ultrasonography, we found that resistive index and pulsatility index were elevated in young Eln +/- and aged mice. Histological examination showed thinner internal and external elastic laminae, accompanied by increased elastin fragmentation in the medial layer without any calcium deposits in the small intrarenal arteries of kidneys from young Eln +/- and aged mice. Pressure myography of interlobar arteries showed that vessels from young Eln +/- and aged mice had a slight decrease in distensibility during pressure loading but a substantial decline in vascular recoil efficiency upon pressure unloading. To examine whether structural changes in the renal microvasculature influenced renal hemodynamics, we clamped neurohumoral input and increased renal perfusion pressure by simultaneously occluding the superior mesenteric and celiac arteries. Increased renal perfusion pressure caused robust changes in blood pressure in all groups; however, changes in renal vascular resistance and renal blood flow (RBF) were blunted in young Eln +/- and aged mice, accompanied by decreased autoregulatory index, indicating greater impairment of renal autoregulation. Finally, increased pulse pressure in aged Eln +/- mice positively correlated with high renal blood flow. Together, our data show that the loss of elastin negatively affects the structural and functional integrity of the renal microvasculature, ultimately worsening age-related decline in kidney function.

Differential central integration of left versus right baroreceptor afferent input in spontaneously hypertensive rats.

The blood pressure (BP) regulatory impact of the arterial baroreflex has been well established in health and disease. Under normotensive conditions, we have previously demonstrated functional differences in the central processing of the left versus right aortic baroreceptor afferent input. However, it is unknown if lateralization in aortic baroreflex function remains evident during hypertension. We therefore, investigated the effects of laterality on the expression of baroreflex-driven cardiovascular reflexes in a genetic model of essential hypertension, the spontaneously hypertensive rat (SHR). Anesthetized male SHRs (total n = 9) were instrumented for left, right, and bilateral aortic depressor nerve (ADN) stimulation (1-40 Hz, 0.2 ms, and 0.4 mA for 20 s) and measurement of mean arterial pressure (MAP), heart rate (HR), mesenteric vascular resistance (MVR), and femoral vascular resistance (FVR). Left right, and bilateral ADN stimulation evoked frequency-dependent decreases in MAP, HR, MVR, and FVR. Left and bilateral ADN stimulation evoked greater reflex reductions in MAP, HR, MVR, and FVR compared with right-sided stimulation. Reflex bradycardia to bilateral stimulation was larger relative to both left-sided and right-sided stimulation. Reflex depressor and vascular resistance responses to bilateral stimulation mimicked those of the left-sided stimulation. These data indicate a left-side dominance in the central integration of aortic baroreceptor afferent input. Furthermore, reflex summation due to bilateral stimulation is only evident on the reflex bradycardic response, and does not drive further reductions in BP, suggesting that reflex depressor responses in the SHRs are primarily driven by changes in vascular resistance. Together, these results indicate that lateralization in aortic baroreflex function is not only evident under normotensive conditions but also extends to hypertensive conditions.

Refined Balloon Pulmonary Angioplasty in Chronic Thromboembolic Pulmonary Hypertension: Initial Results of U.S. Regional Program

BackgroundBalloon pulmonary angioplasty (BPA) is rapidly evolving therapeutic option for patients with nonsurgical chronic thromboembolic pulmonary hypertension (CTEPH). There are few U.S. studies that have reported on the outcomes of this novel therapeutic option. ObjectivesThe authors sought to evaluate the efficacy and safety of refined BPA in the treatment of patients with CTEPH. MethodsThis is a retrospective study of CTEPH patients that underwent BPA. The primary efficacy endpoint was the change in pulmonary vascular resistance after BPA as compared to baseline and the primary safety endpoint was the rate of hemoptysis within 24 hours. Secondary endpoints included death, World Health Organization functional class, and 6-minute walk distance. Logistic regression was used to evaluate factors associated with a hemodynamic and functional response. ResultsA total of 211 BPA sessions were performed on 77 patients (average 2.7 ± 1.7 sessions/patient). After BPA the mean pulmonary vascular resistance improved by 26% (6.5 ± 3.4 WU to 4.8 ± 2.9 WU, P < 0.001). The mean 6-minute walk distance improved by 71.7 m (P < 0.001), and WHO functional class improved by 1 functional class (P < 0.001). There was one death related to reperfusion lung injury. Ten sessions (4.7%) were complicated by hemoptysis. Independent factors associated with improved functional and hemodynamic response included preprocedural use of riociguat, reduce baseline PA compliance, and >3 BPA sessions/patient. ConclusionsThis single center study from the United States showed that BPA with refined techniques in patients with CTEPH was relatively safe and was associated with significant improvements in pulmonary hemodynamics and functional capacity.

Arterial hypotension: epidemiology, etiopathogenesis, symptomatology, and diagnosis

Arterial hypotension is a systemic hemodynamic disorder that is defined as a decrease in blood pressure below 90/60 mm Hg, caused by changes in cardiac output or systemic vascular resistance or both of these values, and that can lead to organ and tissue hypoperfusion. The review considers the epidemiology, etiology, and pathogenesis of this condition. Particular attention is paid to the classification of hypotension based on various biometric parameters, by the rate of occurrence and time of exposure, taking into account the impact on organ perfusion. The symptomatology and diagnosis of hypotension are analyzed; its complications are described.

Mechanism of Increased Spinal Cord Blood Flow due to Noradrenaline Administration Using Vascular Resistance: An Experimental Study Using a Canine Model

During thoracoabdominal aortic surgery, the spinal cord is placed under ischemic conditions. Elevation of systemic blood pressure is thus recommended as a method of increasing the blood supply from collateral networks. This study examined the mechanisms by which noradrenaline administration increases spinal cord blood flow (SCBF) by elevating systemic blood pressure. In beagles (n = 7), the thoracoabdominal aorta and L2-L7 spinal cord segmental arteries (SAs) were exposed and a distal perfusion bypass was created to simulate clinical practice. SCBF was measured by laser flowmetry at the L5 dura mater and spinal cord perfusion pressure (SCPP) was measured inside the clamped aorta. The six pairs of SAs from L2 to L7 were clamped, and mean systemic blood pressure (mSBP), SCBF, and SCPP were measured before and after clamping and after starting continuous infusion of noradrenaline at 0.5 µg/kg/min. Rates of change in systemic vascular resistance (SVR) and spinal cord vascular resistance (SCVR) were calculated from the measured values. With no SA clamping (control), the rate of increase in SCVR was 0.74 times the rate of increase in SVR (y = 0.2 + 0.74x, r = 0.889, r2 = 0.789; P < 0.01). When all six pairs of SAs were clamped, a weak correlation was evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.39 + 0.07x, r = 0.209, r2 = 0.039; P < 0.01). When all six pairs of SAs were clamped in the absence of distal perfusion, a weak correlation was also evident between rate of change in SCVR and rate of change in SVR, and the rate of increase in SCVR was lower than the rate of increase in SVR (y = 0.19 + 0.08x, r = 0.379, r2 = 0.144; P < 0.01). The rate of increase in SCVR induced by noradrenaline administration was lower than the rate of increase in SVR in the control group with no spinal cord SA clamping and in both experimental groups with clamped SAs (with and without distal perfusion), creating an environment conducive to spinal cord flow distribution.

Phase 3 Trial of Sotatercept for Treatment of Pulmonary Arterial Hypertension

BackgroundPulmonary arterial hypertension is a progressive disease involving proliferative remodeling of the pulmonary vessels. Despite therapeutic advances, the disease-associated morbidity and mortality remain high. Sotatercept is a fusion protein that traps activins and growth differentiation factors involved in pulmonary arterial hypertension.MethodsWe conducted a multicenter, double-blind, phase 3 trial in which adults with pulmonary arterial hypertension (World Health Organization [WHO] functional class II or III) who were receiving stable background therapy were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. Nine secondary end points, tested hierarchically in the following order, were multicomponent improvement, change in pulmonary vascular resistance, change in N-terminal pro–B-type natriuretic peptide level, improvement in WHO functional class, time to death or clinical worsening, French risk score, and changes in the Pulmonary Arterial Hypertension–Symptoms and Impact (PAH-SYMPACT) Physical Impacts, Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores; all were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit.ResultsA total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, −0.3 to 3.5) in the placebo group. The Hodges–Lehmann estimate of the difference between the sotatercept and placebo groups in the change from baseline at week 24 in the 6-minute walk distance was 40.8 m (95% CI, 27.5 to 54.1; P<0.001). The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.ConclusionsIn patients with pulmonary arterial hypertension who were receiving stable background therapy, sotatercept resulted in a greater improvement in exercise capacity (as assessed by the 6-minute walk test) than placebo. (Funded by Acceleron Pharma, a subsidiary of MSD; STELLAR ClinicalTrials.gov number, NCT04576988.)

Increased cerebral vascular resistance underlies preserved cerebral blood flow in response to orthostasis in humans on a high-salt diet.

Cerebral blood flow autoregulation protects brain tissue from blood pressure variations and maintains cerebral perfusion pressure by changes in vascular resistance. High salt (HS) diet impairs endothelium-dependent vasodilation in many vascular beds, including cerebral microcirculation, and may affect vascular resistance. The aim of present study was to determine if 7-day HS diet affected the reactivity of middle cerebral artery (MCA) to orthostatic challenge in healthy human individuals, and if autoregulatory mechanisms and sympathetic neural regulation were involved in this phenomenon.Twenty-seven persons participated in study (F:21, M:6, age range 19-24). Participants consumed 7-day low-salt (LS) diet (< 2.3g kitchen salt/day) and afterwards 7-day HS diet (> 11.2g kitchen salt/day). Blood and urine analysis and anthropometric measurements were performed after each diet. Arterial blood pressure, heart rate and heart rate variability, and cerebral and systemic hemodynamic parameters were recorded simultaneously with transcranial Doppler ultrasound and The Task Force®Monitor in response to orthostatic test.Participants remained normotensive during HS diet. Following both, the LS and HS dietary protocols, mean cerebral blood flow (CBF), as well as the velocity time integral and diastolic blood pressure decreased, and cerebral pulsatility index increased after rising up. Importantly, cerebrovascular resistance significantly increased in response to orthostasis only after HS diet. Urine concentration of noradrenaline and vanillylmandelic acid, baroreflex sensitivity (BRS), and sympathetic neural control was significantly decreased in HS diet.Results suggest that CBF in response to orthostatic test was preserved in HS condition due to altered vascular reactivity of MCA, with increased cerebrovascular resistance and blunted BRS and sympathetic activity.

규칙적인 웨이트트레이닝이 비만 남성의 혈관계 변인 및 스트레스호르몬에 미치는 영향

In this study, to analyze the effect of regular weight training on the vascular variable and stress hormones, the body fat was measured using In body 3.0 in obese men consisting of 10 obese experimental group and 10 control group, and ultrasound Doppler technique. As a result of measuring and analyzing arterial blood flow velocity and vascular resistance and stress hormone variables such as epinephrine and norepinephrine, the experimental group showed a decrease ratio of -15.6% for each treatment period, and the change in the control group by period. there was no Vascular resistance showed a high reduction ratio of -25.2% by treatment period in the experimental group, and there was no change in the control group by period. In the case of epinephrine, there was no change in the control group, and the experimental group showed a rather low increase ratio of -6.03% by treatment period, but there was no statistically significant difference. As for norepinephrine, compared to the control group by period, the experimental group showed a high reduction ratio of -24.5%. As a result, the blood flow rate and vascular resistance decreased through the reduction of the stress hormone in obese men, so it was adapted to long-term weight training. Changes in blood flow rate and vascular resistance and stress hormones were observed. Therefore, the weight training presented in this study is interpreted as having a positive effect on the improvement of blood flow rate and changes in the stress hormones epinephrine and norepinephrine, along with relieving obesity in men. In order to improve the functional improvement and prevent clinical diseases, we would like to recommend a weight training program with a high repetition concept.

Pulmonary arterial compliance and exercise capacity after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

To determine whether changes in pulmonary vascular resistance (PVR) and changes in pulmonary artery compliance (C pa) are associated with changes in exercise capacity assessed either by changes in peak oxygen consumption (V'O2 ) or by changes in 6-min walk distance (6MWD) in patients with chronic thromboembolic pulmonary hypertension (CTEPH) undergoing balloon pulmonary angioplasty (BPA). Invasive haemodynamic parameters, peak V'O2 and 6MWD were measured within 24 h, before and after BPA (interval 3.1±2.4 months) in 34 CTEPH patients without significant cardiac and/or pulmonary comorbidities, of whom 24 received at least one pulmonary hypertension-specific treatment. C pa was calculated according to the pulse pressure method: C pa=((SV/PP)/1.76+0.1), where SV is the stroke volume and PP is the pulse pressure. The resistance-compliance (RC)-time of the pulmonary circulation was calculated as the PVR and C pa product. After BPA, PVR decreased (562±234 versus 290±106 dyn·s·cm-5; p<0.001); C pa increased (0.90±0.36 versus 1.63±0.65 mL·mmHg-1; p<0.001); but RC-time did not change (0.325±0.069 versus 0.321±0.083 s; p=0.75). There were improvements in peak V'O2 (1.11±0.35 versus 1.30±0.33 L·min-1; p<0.001) and in 6MWD (393±119 versus 432±100 m; p<0.001). After adjustment for age, height, weight and gender, changes in exercise capacity, assessed either by peak V'O2 or 6MWD, were significantly associated with changes in PVR, but not with changes in C pa. Contrary to what has been reported in CTEPH patients undergoing pulmonary endarterectomy, in CTEPH patients undergoing BPA, changes in exercise capacity were not associated with changes in C pa.

Favorable effect of renal denervation on elevated renal vascular resistance in patients with resistant hypertension and type 2 diabetes mellitus.

To assess the effect of renal denervation (RDN) on renal vascular resistance and renal function in patients with drug-resistant hypertension (HTN) and type 2 diabetes mellitus (T2DM). Fifty-nine patients (mean age 60.3 ± 7.9 years, 25 men) with resistant HTN [mean 24-h ambulatory blood pressure (BP) 158.0 ± 16.3/82.5 ± 12.7 mmHg, systolic/diastolic] and T2DM (mean HbA1c 7.5 ± 1.5%) were included in the single-arm prospective study and underwent RDN. Renal resistive index (RRI) derived from ultrasound Doppler; estimated glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration formula), office and 24-h ambulatory BP were measured at baseline, 6, and 12 months after RDN to evaluate the respective changes in renal vascular resistance, renal function, and BP during treatment. Forty-three patients completed 12 months follow-up. The RRI changed depending on the baseline value. Specifically, the RRI decreased significantly in patients with elevated baseline RRI values ≥ 0.7 {n = 23; -0.024 [95% confidence interval (CI): -0.046, -0.002], p = 0.035} and did not change in those with baseline RRI < 0.7 [n = 36; 0.024 (95% CI: -0.002, 0.050), p = 0.069]. No significant change was observed in eGFR whereas BP was significantly reduced at 12 months after RDN by -10.9 (95% CI: -16.7, -5.0)/-5.5 (95% CI: -8.7, -2.4) mmHg, systolic/diastolic. No relationship was found between the changes in RRI and BP. Our study shows that RDN can decrease elevated renal vascular resistance (RRI > 0.7) and stabilize kidney function in patients with RHTN and T2DM independently of its BP-lowering effect.

β3 adrenergic agonist treatment in chronic pulmonary hypertension associated with heart failure (SPHERE-HF): a double blind, placebo-controlled, randomized clinical trial.

Pulmonary hypertension (PH) associated with left heart disease is an increasingly prevalent problem, orphan of targeted therapies, and related to a poor prognosis, particularly when pre- and post-capillary PH combine. The current study aimed to determine whether treatment with the selective β3 adrenoreceptor agonist mirabegron improves outcomes in patients with combined pre- and post-capillary PH (CpcPH). The β3 Adrenergic Agonist Treatment in Chronic Pulmonary Hypertension Secondary to Heart Failure (SPHERE-HF) trial is a multicentre, randomized, parallel, placebo-controlled clinical trial that enrolled stable patients with CpcPH associated with symptomatic heart failure. A total of 80 patients were assigned to receive mirabegron (50 mg daily, titrated till 200 mg daily, n=39) or placebo (n=41) for 16 weeks. Of them, 66 patients successfully completed the study protocol and were valid for the main analysis. The primary endpoint was the change in pulmonary vascular resistance (PVR) on right heart catheterization. Secondary outcomes included the change in right ventricular (RV) ejection fraction by cardiac magnetic resonance or computed tomography, other haemodynamic variables, functional class, and quality of life. The trial was negative for the primary outcome (placebo-corrected mean difference of 0.62 Wood units, 95% confidence interval [CI] -0.38, 1.61, p=0.218). Patients receiving mirabegron presented a significant improvement in RV ejection fraction as compared to placebo (placebo-corrected mean difference of 3.0%, 95% CI 0.4, 5.7%, p=0.026), without significant differences in other pre-specified secondary outcomes. SPHERE-HF is the first clinical trial to assess the potential benefit of β3 adrenergic agonists in PH. The trial was negative since mirabegron did not reduce PVR, the primary endpoint, in patients with CpcPH. On pre-specified secondary outcomes, a significant improvement in RV ejection fraction assessed by advanced cardiac imaging was found, without differences in functional class or quality of life.

Impaired Left Ventricular Contractile Reserve in Patients With Hypertrophic Cardiomyopathy and Abnormal Blood Pressure Response: A Stress Echocardiographic Study.

Abnormal blood pressure response (ABPR) has been reported to be a risk factor for sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). We aimed to elucidate the relationship between ABPR during exercise stress echocardiography (ESE) and impaired left ventricular (LV) contractile reserve based on two-dimensional strain in patients with HCM. Patients with HCM underwent ESE with treadmill exercise. Patients whose blood pressure elevation at maximum workload was lower than 20 mmHg from baseline were classified as having ABPR. Echocardiographic parameters were compared between patients with and without ABPR. Results: Of 26 patients with HCM, nine patients were diagnosed with ABPR. Significant LV outflow tract obstruction (>50 mmHg) was provoked only in one patient with ABPR (baseline to the conclusion of the exercise, 15.2 mmHg to 63.0 mmHg). Change in cardiac output (CO) and the ratio of early diastolic velocity to early annular velocity (E/e') from baseline to just after the conclusion of exercise did not differ between patients with and without ABPR (CO, 102±40% vs. 122±45%, P = 0.19; E/e', 4±22% vs. 2±20%, P = 0.86). Change in systemic vascular resistance change was not significant (patients with vs. without ABPR, -52±10% vs. -46±13%, P = 0.24). Percent change in LV global longitudinal strain was lower in patients with ABPR than patients without ABPR (12±17% vs. 27±15%, P = 0.02). In conclusion, impaired LV contractile reserve during exercise might contribute to ABPR in patients with HCM.

Cuffless Blood Pressure Estimation During Moderate- and Heavy-Intensity Exercise Using Wearable ECG and PPG.

To develop and evaluate an accurate method for cuffless blood pressure (BP) estimation during moderate- and heavy-intensity exercise. Twelve participants performed three cycling exercises: a ramp-incremental exercise to exhaustion, and moderate and heavy pseudorandom binary sequence exercises on an electronically braked cycle ergometer over the course of 21 minutes. Subject-specific and population-based nonlinear autoregressive models with exogenous inputs (NARX) were compared with feedforward artificial neural network (ANN) models and pulse arrival time (PAT) models. Population-based NARX models, (applying leave-one-subject-out cross-validation), performed better than the other models and showed good capability for estimating large changes in mean arterial pressure (MAP). The models were unable to track consistent decreases in BP during prolonged exercise caused by reduction in peripheral vascular resistance, since this information is apparently not encoded in the employed proxy physiological signals (electrocardiography and forehead PPG) used for BP estimation. Nevertheless, the population-based NARX model had an error standard deviation of 11.0 mmHg during the entire exercise window, which improved to 9.0 mmHg when the model was periodically calibrated every 7 minutes. Population-based NARX models can estimate BP during moderate- and heavy-intensity exercise but need periodic calibration to account for the change in vascular resistance during exertion. MAP can be continuously tracked during exercise using only wearable sensors, making monitoring exercise physiology more convenient and accessible.