Reduction In Arterial Pressure Research Articles

Effects of pulmonary hypertension targeted therapy on haemodynamics in pulmonary arterial hypertension associated with adult congenital heart disease: a meta-analysis

Abstract Background Pulmonary arterial hypertension (PAH) in adult patients with congenital heart disease (CHD) is associated with increased morbidity and mortality. There is growing evidence that PAH drugs lead to improved hemodynamics, exercise capacity, quality of life and survival in patients with PAH. Purpose The aim of this systematic review and meta-analysis is to evaluate the effects of pulmonary hypertension (PH) medical therapy on the haemodynamic parameters as well as exercise capacity in adult patients with PAH-CHD. Methods PubMed and the Cochrane Library databases have been systematically searched. Meta-analysis was conducted using STATA and Review Manager. Results Fourteen studies including 575 patients were analyzed. Pulmonary haemodynamics improved in patients receiving PH-targeted therapy. The weighted mean reduction in mean pulmonary arterial pressure (mPAP) was -5.8mmHg (I2=0%, 95% CI [–7.55, –4.06], p<0.001).The weighted mean reduction in right atrial pressure (RAP) was -5.81mmHg (I2=0%, 95% CI [-7.55, - 4,07], p<0.001). The weighted mean reduction in pulmonary vascular resistance (PVR) was 358.5dynes/sec/cm-5 (I2 51%, 95% CI [-566.55, -150.46] and p<0.001). Cardiac index was increased by 0.61L/min/m2 (I2=6%, 95% CI [0.23,1.00], p=0.002). Six-minute walking distance increased by 47.26m, (I2=0%, CI [38.36, 56.16], p<0.001). Conclusions PH-targeted therapy improves pulmonary haemodynamics and exercise capacity in adult patients with PAH-CHD.

Development of a new micellar formulation of carvedilol and curcumin to enhance blood pressure reduction in a spontaneously hypertensive rat model.

Cardiovascular diseases remain a leading cause of morbidity and mortality worldwide, requiring innovative therapeutic strategies. This project explores a nano-pharmaceutical approach to enhance the efficacy of cardiovascular drugs, focusing on carvedilol and curcumin. These agents, known for their potential cardiovascular benefits, are encapsulated within Soluplus® micelles to form a novel drug delivery system. The novelty of this formulation lies in its ability to significantly improve the solubility of both carvedilol and curcumin, which have traditionally been limited by their hydrophobic nature. By utilizing Soluplus® micelles, we have developed a unique delivery system that optimizes the therapeutic potential of both drugs. The nanomicelles were meticulously characterized for drug loading, size distribution, and morphological features. The carvedilol and curcumin release patterns were investigated, revealing sustained and controlled release profiles. Additionally, the antioxidant capacity of the micellar formulation was evaluated, demonstrating the preservation of curcumin's antioxidative properties. In vivo studies using spontaneously hypertensive male rats explored the pharmacokinetics and hemodynamic effects of the nanomicellar system. These results indicated successful encapsulation of both drugs without altering their plasma profiles. Furthermore, the administration of carvedilol and curcumin micelles exhibited a more significant reduction in mean arterial pressure compared to individual drug administration, suggesting a potential synergistic effect. In conclusion, this nano-pharmaceutical approach offers a promising avenue for cardiovascular therapy, providing a platform for combined drug delivery and potential synergistic effects. The optimized formulation could lead to improved patient outcomes and enhanced cardiovascular health.

L-Arginine and Taurisolo® Effects on Brain Hypoperfusion-Reperfusion Damage in Hypertensive Rats.

Acute and chronic hypertension causes cerebral vasculopathy, increasing the risk of ischemia and stroke. Our study aimed to compare the effects of arterial pressure reduction on the pial microvascular responses induced by hypoperfusion and reperfusion in spontaneously hypertensive Wistar rats, desamethasone-induced hypertensive Wistar rats and age-matched normotensive Wistar rats fed for 3 months with a normal diet or normal diet supplemented with L-arginine or Taurisolo® or L-arginine plus Taurisolo®. At the end of treatments, the rats were submitted to bilateral occlusion of common carotid arteries for 30 min and reperfusion. The microvascular parameters investigated in vivo through a cranial window were: arteriolar diameter changes, permeability increase, leukocyte adhesion to venular walls and percentage of capillaries perfused. Hypoperfusion-reperfusion caused in all rats marked microvascular changes. L-arginine treatment was effective in reducing arterial blood pressure causing vasodilation but did not significantly reduce the damage induced by hypoperfusion-reperfusion. Taurisolo® treatment was less effective in reducing blood pressure but prevented microvascular damage from hypoperfusion-reperfusion. L-arginine plus Taurisolo® maintained blood pressure levels within the physiological range and protected the pial microcirculation from hypoperfusion-reperfusion-induced microvascular injuries. Therefore, the blood pressure reduction is not the only fundamental aspect to protect the cerebral circulation from hypoperfusion-reperfusion damage.

Efficacy and safety of fenoldopam for the treatment of hypertensive crises in children with kidney disease: a retrospective study.

Hypertensive crises in children represent critical medical situations characterized by severe hypertension and potential organ damage. Fenoldopam, a dopaminergic medication, offers a viable therapeutic option for managing such clinical scenarios. We aimed to evaluate efficacy and safety of fenoldopam in the management of hypertensive urgencies and emergencies. This retrospective analysis focused on pediatric patients affected by acute or chronic kidney disease, aged 1month-18years, admitted to the Pediatric Nephrology and the Pediatric Intensive Care Unit at University-Hospital of Padua, Italy, who presented witha hypertensive crisis treated with fenoldopam between March 2010 and December 2022. The study included 74 patients with median age 10years (interquartile range [IQR] 4-15years) who received 102 fenoldopam infusions. Seventy-two percent were already receiving antihypertensive treatment before admission. In all cases, fenoldopam was associated with a reduction of blood pressure (BP) after 8h of treatment, but in 87% of patients reduction of the initial mean arterial pressure (MAP) was higher than 25% of calculated drop pressure. MAP normalized in 26% of cases after 24h and in35% after 48h. Occurrence of hypotension was 7%, while hypokalemia was observed in 13% of cases. Patients who presented a MAP reduction not exceeding 25% of calculated drop pressure received a lower median fenoldopam dose (0.2 mcg/kg/min; IQR 0.1-0.2) compared with patients having a MAP reduction > 25% of calculated drop pressure (0.4 mcg/kg/min; IQR 0.2-0.6; p = 0.002). Fenoldopam seems effective and safe for the treatment of hypertensive crises in children with kidney disease, at a starting dose of 0.2 mcg/kg/min. Strict BP monitoring is required to identify possible excessive drop pressure in the first hours of infusion.

Post‐intubation hypotension risk factors in patients with COVID‐19 undergoing endotracheal intubation in the emergency department: A prospective observational study

AbstractIntroductionAcute respiratory distress syndrome, a severe manifestation of COVID‐19, prompts the critical intervention of endotracheal intubation (ETI). However, ETI is associated with complications, notably post‐intubation hypotension (PIH), linked to an increased adverse prognosis. Our purpose was to investigate risk factors for PIH in COVID‐19 patients in the emergency department (ED).MethodsThis observational study was conducted at the Afzalipour Hospital, Iran. Adult COVID‐19 patients undergoing ETI were included, with data collected on demographic variables, medical history, and hemodynamic parameters. PIH was defined as the occurrence of any of the following: reduction of systolic blood pressure (SBP) to 90 mmHg or less; reduction of mean arterial pressure (MAP) to 65 mmHg or less; reduction of SBP by at least 20% of the initial value; or the need for vasopressor support during the 30 min after intubation.ResultsAmong 145 patients, the mortality rate was 82.7%, and PIH occured in 22.7%. Univariate analysis revealed associations between PIH and initial SBP (SBP‐0) and initial MAP. Multivariable regression revealed that each 1 mmHg decrease in SBP‐0 increased the risk of PIH by 5%. Patients with SBP‐0 of less than 116 mmHg had a PIH odds ratio of 4.1. A history of hypertension (HTN) or ischemic heart disease (IHD) increased the likelihood of PIH sixfold. The receiver operating characteristic curves for SBP‐0 had an area under the curve (AUC) of 0.67 (95% CI: 0.54–0.79), lower than the AUC of 0.77 (95% CI: 0.64–0.86) for the model incorporating SBP‐0, history of HTN or IHD, and total severity score. Despite this, the Z score comparing the AUCs of SBP‐0 and the multivariable model did not indicate a statistically significant difference.ConclusionsHistory of HTN or IHD, as well as low SBP‐0, are independently associated with an increased risk of PIH in COVID‐19 patients.

Pressure Support Ventilation During Extracorporeal Membrane Oxygenation Support in Patients With Acute Respiratory Distress Syndrome.

In the initial phases of veno-venous extracorporeal membrane oxygenation (VV ECMO) support for severe acute respiratory distress syndrome (ARDS), ultraprotective controlled mechanical ventilation (CMV) is typically employed to limit the progression of lung injury. As patients recover, transitioning to assisted mechanical ventilation can be considered to reduce the need for prolonged sedation and paralysis. This study aimed to evaluate the feasibility of transitioning to pressure support ventilation (PSV) during VV ECMO and to explore variations in respiratory mechanics and oxygenation parameters following the transition to PSV. This retrospective monocentric study included 191 adult ARDS patients treated with VV ECMO between 2009 and 2022. Within this population, 131 (69%) patients were successfully switched to PSV during ECMO. Pressure support ventilation was associated with an increase in respiratory system compliance (p = 0.02) and a reduction in pulmonary shunt fraction (p < 0.001). Additionally, improvements in the cardiovascular Sequential Organ Failure Assessment score and a reduction in pulmonary arterial pressures (p < 0.05) were recorded. Ninety-four percent of patients who successfully transitioned to PSV were weaned from ECMO, and 118 (90%) were discharged alive from the intensive care unit (ICU). Of those who did not reach PSV, 74% died on ECMO, whereas the remaining patients were successfully weaned from extracorporeal support. In conclusion, PSV is feasible during VV ECMO and potentially correlates with improvements in respiratory function and hemodynamics.

Large-bore Aspiration Thrombectomy with the FlowTriever System for the Treatment of Pulmonary Embolism: A Large Single-Center Retrospective Analysis

PurposeEvaluate the outcomes of patients undergoing large-bore aspiration thrombectomy for the treatment of pulmonary embolism at a large university medical center.Materials and methodsAll patients treated for pulmonary embolism with the FlowTriever System (Inari Medical, Irvine, CA) between September 2019 and January 2023 were retrospectively analyzed. The primary safety and effectiveness outcomes included 7- and 30-day all-cause mortality, major bleeding, procedure-associated clinical decompensation, pulmonary vascular or cardiac injury, and pulmonary artery pressure reduction. Additional outcomes included technical success (completing thrombectomy with the device as intended), changes in hemodynamics and supplemental oxygen requirements, and postprocedural intensive care unit stay.ResultsA total of 286 patients were identified. The mean age was 60.5 years, and 90.9% of patients presented with intermediate-risk pulmonary embolism. Technical success was achieved in 96.9% (n = 277) of cases. The average reduction in mean pulmonary arterial pressure was 6.8 mmHg, from 28.7 ± 9.0 to 21.9 ± 8.0 mmHg (p < 0.0001). Two major bleeds (0.7%), 2 pulmonary vascular injuries (0.7%), and 4 (1.4%) procedure-associated decompensations were reported, but no device-related deaths occurred. The mean post-procedure intensive care unit stay was 2.0 ± 4.1 days, and 49.3% of patients had no postprocedural intensive care unit admittance. The overall 7-day and 30-day all-cause mortality rates were 2.4% and 6.7%, respectively, with a 30-day pulmonary embolism-related mortality rate of 3.5%.ConclusionThis non-industry-sponsored single-center analysis of large-bore aspiration thrombectomy in a large population corroborates the findings of other studies and confirms that this approach is safe and effective for the treatment high- and intermediate-risk pulmonary embolism.Level of Evidence IVRetrospective observational study.Graphical

Use of Dexmedetomidine versus Nitroglycerine to Provide Hypotensive Anesthesia in ENT Surgeries (Functional Endoscopic Sinus Surgery)

Abstract Background controlled (deliberate/induced) hypotension is a technique by which the arterial blood pressure is lowered in a controllable manner to reduce surgical blood loss and improve the operative field visibility. There are pharmacological and nonpharmacological techniques for inducing hypotension. The nonpharmacological methods for deliberate hypotension include positioning and positive pressure ventilation to control venous return. Aim of the Work to evaluate the efficacy of dexmedetomidine (DEX) as a hypotensive agent in comparison to nitroglycerin (NTG) in FESS regarding the bloodless field, reduction of mean arterial blood pressure, decrease inhalational anesthetic requirements (MAC), decrease perioperative opioid requirements, increase the time to first postoperative analgesic request and recovery profile and increase hemodynamics stability. Patients and Methods we conducted this study on 20 patients who were planned to perform functional endoscopic sinus surgery and were randomly distributed into 2 equal groups: 10 patients received dexamedotomidine and equal number of patients received nitroglycerine. Serial measurements of mean arterial blood pressure and heart rate were obtained and records between both groups were compared. Results There were statistically significant differences between both groups regarding heart rate as mean values of heart rate were lower among dexamedotomidine group. There were no statistically significant differences between both groups regarding mean arterial blood pressure values at different time points during the operation. Regarding the period after stopping infusion, mean values of heart rate and blood pressure were lower among dexamedotomidine group than nitroglycerine group after 5 minutes and after 10 minutes and the differences had statistically significant differences. Regarding postoperative period, both groups were comparable regarding heart rate and blood pressure immediately postoperative. Conclusion From the results of this study, we could conclude that both Dexmedetomidine and Nitroglycerin can be effectively used in induced hypotensive anesthesia for ENT surgery as FESS. Both groups were comparable with intra operative MAP with no statistically significant differences. This study also show that Dexmedetomidine has added advantages as better haemodynamic stability than Nitroglycerin (No rebound HTN, no tachycardia). Has sedative and analgesic effect, reduce requirement of anesthetic agents and perioperative analgesia. Postoperative recovery score (Time to reach modified Aldert score more than nine significantly higher. Postoperative complication as nausea and vomiting is less.

Safety and Efficacy of SGLT2 Inhibitors for Amyloid Light-Chain Cardiomyopathy

BackgroundSodium-glucose cotransporter-2 inhibitors (SGLT2i) have demonstrated benefit in patients with heart failure, but minimal data exists around the use of these medications in amyloid light-chain cardiomyopathy (AL-CM). We performed a retrospective study assessing the safety and efficacy of SGLT2i in AL-CM. MethodsWe queried our institutional registry and identified 27 AL-CM patients who received SGLT2i. The safety analysis included all 27 patients and assessed SGLT2i-associated adverse events, hospitalizations, and deaths. To decrease confounding, the efficacy analysis included only a subset of patients with stable disease (on stable anti-plasma cell therapy for ≥2 months prior to baseline and achieved at least a hematologic Very Good Partial Response) and compared disease marker changes in these patients (n=17) with those of a contemporaneous untreated control cohort from our registry (n=21). ResultsThe mean age of the overall population was 68.6 (standard deviation 9.4) years. Seven (14.6%) patients had diabetes, and 19 (39.6%) had chronic kidney disease. In the safety analysis, median follow-up time was 10.9 (interquartile range 7.2) months. Two (7.4%) patients discontinued SGLT2i due to hypovolemia and genital irritation, and 6 (22.2%) additional patients temporarily held SGLT2i due to an adverse event, commonly related to volume depletion. Thirteen hospitalizations, all considered unrelated to SGLT2i use, and no deaths occurred. In the efficacy analysis, SGLT2i-treated patients had more severe disease at baseline than controls, demonstrating significantly higher median troponin-T and loop diuretic dose (P<0.05). Compared with controls, SGLT2i treatment was associated with significantly greater reductions in loop diuretic dose (P<0.001) and NTproBNP (P=0.033) across 3-, 6-, and 12-month follow-up timepoints. SGLT2i treatment was also associated with a significantly greater reduction in mean arterial pressure at 12 months (P=0.031) but not at other timepoints. No significant differences were observed on changes in weight, eGFR, troponin-T, proteinuria, or albumin. ConclusionsIn this small-scale retrospective study, we demonstrate that SGLT2i is well-tolerated by most patients with AL-CM, but volume depletion symptoms may limit continuous use. SGLT2i may aid management of congestion in AL-CM as evidenced by reduced diuretic dose and NTproBNP without adverse renal effects. Larger long-term studies are needed to build on our findings.

The Antihypertensive Effect of Marchin-13 Tang on L-NAME-induced Hypertension in Rats

Marchin-13 Tang is a traditional Mongolian medicine widely used to reduce blood pressure. The study aimed to evaluate the anti-hypertensive effect of Marchin-13 (M-13) Tang in the L-NAME-induced model of hypertension. The biological composition activity of M-13 Tang was examined using the UV spectrophotometric method. The experimental groups induced Hypertension models by L-NAME 40 mg/kg. The concentrations of serum nitric oxide (NO), Angiotensin-Converting Enzyme (ACE), superoxide dismutase (SOD), malondialdehyde (MDA), and catalase (CAT) were measured in M-13 Tang treatment groups by enzyme-linked immunosorbent assay (ELISA). The content of total phenolics was measured at 2.96±0.16%, while flavonoids were found to be present at a level of 1.81±0.1%. The reductions in mean arterial pressure (MAP) were statistically significant. They were observed from day 14 to day 21 after giving M-13 Tang at 90 mg/kg and 180 mg/kg (p&lt;0.01). Moreover, treated with M-13 Tang 90 mg/kg and 180 mg/kg groups, serum levels of NO, SOD, and CAT were significantly (p&lt;0.01) increased compared with the L-NAME (40 mg/kg) group. The levels of MDA and ACE showed a significant decrease in both the Marchin-13 Tang-treated groups compared to the L-NAME group (p&lt;0.05). The results of our study illustrate that Marchin-13 effectively reduced blood pressure by mitigating oxidative stress, enhancing NO production, and decreasing ACE levels in hypertensive rats induced by L-NAME.

NO-cGMP-K+ Channels Pathways Participate in the Antihypertensive Effects of Attalea phalerata Martius ex Spreng Oil-Loaded Nanocapsules.

Attalea phalerata Martius ex Spreng is a palm tree that is widely distributed in the Central-West region of Brazil. In this study, we investigated whether the oil-loaded nanocapsules of A. phalerata (APON) have acute and long-lasting antihypertensive effects in male spontaneously hypertensive rats (SHR), as well as explored the underlying molecular mechanisms. APON was prepared using the interfacial polymer deposition method. The particle size, polydispersity index, and zeta potential were investigated using dynamic and electrophoretic light scattering. The antihypertensive effects of APON (administered at doses of 1, 3, and 10 mg/kg) were evaluated after acute intraduodenal administration and after 7 days of oral treatment. To investigate the molecular pathways involved, we used pharmacological antagonists and inhibitors that target prostaglandin/cyclic adenosine monophosphate, nitric oxide/cyclic guanosine monophosphate, and potassium channels. Both acute and prolonged administration of APON (at doses of 3 and 10 mg/kg) resulted in a significant reduction in systolic, diastolic, and mean arterial pressure. Prior treatment with a non-selective nitric oxide synthase inhibitor (Nω-nitro-L-arginine methyl ester), guanylyl cyclase inhibitor (methylene blue), or non-selective calcium-sensitive K+ channel blocker (tetraethylammonium) abolished the antihypertensive effects of APON. Our study showed that A. phalerata oil-loaded nanocapsules have a significant antihypertensive effect in SHR after both short-term and long-term (7-day) use. This effect seems to rely on the vascular endothelium function and involves the NO-cGMP-K+ channel pathway. This research suggests a new direction for future studies to definitively prove the therapeutic benefits of APON in treating cardiovascular disease.

Haemodynamic, hormonal and renal actions of osteocrin in normal sheep.

Osteocrin (OSTN) is an endogenous protein sharing structural similarities with the natriuretic peptides [NPs; atrial (ANP), B-type (BNP) and C-type (CNP) NP], which are hormones known for their crucial role in maintainingpressure/volume homeostasis. Osteocrin competes with the NPs for binding to the receptor involved in their clearance (NPR-C). In the present study, having identified, for the first time, the major circulating form of OSTN in human and ovine plasma, we examined the integrated haemodynamic, endocrine and renal effects of vehicle-controlled incremental infusions of ovine proOSTN (83-133) and its metabolism in eight conscious normal sheep. Incremental i.v. doses of OSTN produced stepwise increases in circulating concentrations of the peptide, and its metabolic clearance rate was inversely proportional to the dose. Osteocrin increased plasma levels of ANP, BNP and CNP in a dose-dependent manner, together with concentrations of their intracellular second messenger, cGMP. Increases in plasma cGMP were associated with progressive reductions in arterial pressure and central venous pressure. Plasma cAMP, renin and aldosterone were unchanged. Despite significant increases in urinary cGMP levels, OSTN administration was not associated with natriuresis or diuresis in normal sheep. These results support OSTN as an endogenous ligand for NPR-C in regulating plasma concentrations of NPs and associated cGMP-mediated bioactivity. Collectively, our findings support a role for OSTN in maintaining cardiovascular homeostasis.

Rho-kinase inhibition reduces systolic blood pressure and forearm vascular resistance in healthy older adults: a double-blind, randomized, placebo-controlled pilot study.

Rho-kinase has been implicated in the development of hypertension in preclinical studies and may contribute to age-related blood pressure elevation. This study tested the hypothesis that Rho-kinase contributes to elevated systolic blood pressure (SBP) in healthy older adults. Young (18-30 years, 6F/6M) and older (60-80 years, 7F/6M) adults were enrolled in a double-blind, placebo-controlled crossover study using intravenous fasudil infusion to inhibit Rho-kinase. Fasudil lowered SBP in older adults compared to placebo (saline) (2-h post-infusion: 125 ± 4 vs. 133 ± 4 mmHg, P < 0.05), whereas fasudil had no impact on SBP in young adults. Immediately following fasudil infusion, there was a transient reduction in mean arterial pressure (MAP) in young adults that was no longer evident 1-h post-infusion. In older adults, MAP remained lower throughout the fasudil visit compared to placebo (2-h post-infusion: 93 ± 3 vs. 100 ± 3 mmHg, P < 0.05) such that age-related differences in SBP and MAP were abolished. Aortic stiffness (carotid-femoral pulse wave velocity) was not altered by fasudil when central MAP was included as a covariate in analyses. Fasudil reduced forearm vascular resistance in older (2-h post-infusion: 3.3 ± 0.4 vs. 4.8 ± 0.6 mmHg/ml/min, P < 0.05) but not young (4.0 ± 0.6 vs. 3.8 ± 0.5 mmHg/ml/min) adults, which was accompanied by an increase in brachial artery diameter only in older adults. Brachial artery flow-mediated dilation was not affected by fasudil in either group. These findings indicate that Rho-kinase inhibition reduces SBP in healthy older but not young adults, which is associated with a concomitant reduction in forearm vascular resistance.

High-flow nasal cannula oxygen reduced hypoxemia in patients undergoing gastroscopy under general anesthesia at ultra-high altitude: a randomized controlled trial.

Hypoxemia can occur in people at ultra-high altitude (above 3500m) even at rest, and patients undergoing gastroscopy under general anesthesia have higher risk of hypoxemia. Supplementary oxygen via standard nasal cannula (SNC) is the standard of care for most patients who undergo gastroscopy under general anesthesia, which provides oxygen flow up to 15L/min. High-flow nasal cannula (HFNC) could deliver oxygen at a rate up to 60L/min, which is recommended by the American Society of Anesthesiologists Practice Guidelines. We speculated that the benefit with HFNC is more prominent in high-altitude areas, and aimed to compare the incidence of hypoxemia during gastroscopy under general anesthesia at ultra-high altitude with oxygen supply via either HFNC or SNC. The trial was registered at at Chinese Clinical Trial Registry (ChiCTR2100045513; date of registration on 18/04/2021). Adult patients undergoing gastroscopy with anesthesia (estimated duration of anesthesia at ≥ 15min) were randomized at a 1:1 ratio to receive HFNC oxygen or SNC oxygen. The primary outcome was hypoxemia (SpO2 < 90% for any duration). Secondary outcomes included severe hypoxemia (SpO2 < 75% for any duration or SpO2 < 90% but ≥ 75% for ≥ 60s) and hypotension, as defined by reduction of mean arterial blood pressure by ≥ 25% from the baseline. A total of 262 patients were enrolled: 129 in the HFNC group and 133 in the SNC group. All patients received the designated intervention. Student's t-test, Mann-Whitney U test and χ2 test were employed in the study. The rate of hypoxemia was 9.3% (12/129) in the HFNC group versus 36.8% (49/133) in the SNC group [risk ratio (95% confidence interval): 0.25(0.14-0.45); P < 0.001). The HFNC group also had lower rate of severe hypoxemia [0.0% (0/129) versus 11.3% (15/133); risk ratio (95% confidence interval): 0.03(0.00-0.55); P < 0.001, respectively]. The rate of hypotension did not differ between the 2 groups [22.5% (29/129) in HFNC group versus 21.1% (28/133) in SNC group; risk ratio (95% confidence interval): 1.07(0.67-1.69) ; P = 0.779]. HFNC oxygen reduced the incidence of hypoxemia during anesthesia in adult patients undergoing gastroscopy at ultra-high altitude.

ST-2560, a selective inhibitor of the NaV1.7 sodium channel, affects nocifensive and cardiovascular reflexes in non-human primates.

The voltage-gated sodium channel isoform NaV1.7 is a high-interest target for the development of non-opioid analgesics due to its preferential expression in pain-sensing neurons. NaV1.7 is also expressed in autonomic neurons, yet its contribution to involuntary visceral reflexes has received limited attention. The small molecule inhibitor ST-2560 was advanced into pain behaviour and cardiovascular models to understand the pharmacodynamic effects of selective inhibition of NaV1.7. Potency of ST-2560 at NaV1.7 and off-target ion channels was evaluated by whole-cell patch-clamp electrophysiology. Effects on nocifensive reflexes were assessed in non-human primate (NHP) behavioural models, employing the chemical capsaicin and mechanical stimuli. Cardiovascular parameters were monitored continuously in freely-moving, telemetered NHPs following administration of vehicle and ST-2560. ST-2560 is a potent inhibitor (IC50 = 39 nM) of NaV1.7 in primates with ≥1000-fold selectivity over other isoforms of the human NaV1.x family. Following systemic administration, ST-2560 (0.1-0.3 mg·kg-1, s.c.) suppressed noxious mechanical- and chemical-evoked reflexes at free plasma concentrations threefold to fivefold above NaV1.7 IC50. ST-2560 (0.1-1.0 mg·kg-1, s.c.) also produced changes in haemodynamic parameters, most notably a 10- to 20-mmHg reduction in systolic and diastolic arterial blood pressure, at similar exposures. Acute pharmacological inhibition of NaV1.7 is antinociceptive, but also has the potential to impact the cardiovascular system. Further work is merited to understand the role of NaV1.7 in autonomic ganglia involved in the control of heart rate and blood pressure, and the effect of selective NaV1.7 inhibition on cardiovascular function.

Evaluation of the Efficacy and Safety of Nicardipine Versus Clevidipine for Blood Pressure Control in Hypertensive Crisis

BackgroundHypertensive crisis is an acute increase in blood pressure >180/120 mm Hg. A titratable antihypertensive agent is preferred to lower blood pressure acutely in a controlled way and prevent an abrupt overcorrection. Nicardipine and clevidipine are both dihydropyridine calcium channel blockers that provide unique benefits for blood pressure control. ObjectiveThe purpose of this study was to compare the efficacy and safety of nicardipine or clevidipine for blood pressure control in the setting of hypertensive crisis. MethodsThis was a single-center, retrospective cohort study. Eligible patients received either nicardipine or clevidipine for the treatment of hypertensive crisis. The primary outcome was achievement of 25% reduction in mean arterial pressure at 1 h. The secondary outcome was achievement of a systolic blood pressure (SBP) of <160 mm Hg at 2–6 h from the start of the infusion. ResultsThis study included a total of 156 patients, 74 in the nicardipine group and 82 in the clevidipine group. The SBP on admission and at the start of the infusion were similar between groups. There was no difference between groups in achieving a 25% reduction in mean arterial pressure at 1 h. Nicardipine achieved an SBP goal of <160 mm Hg at 2–6 h significantly more often than the clevidipine group (89.2% vs. 73.2%; p = 0.011). ConclusionsThere is no difference between agents for initial blood pressure control in the treatment of hypertensive crisis. Nicardipine showed more sustained SBP control, with a lower risk of rebound hypertension and a significant cost savings compared with clevidipine.

Cerebrovascular Compliance during Progressive Hypotension in Patients with Autonomic Failure

Background: Cerebral perfusion during reductions in arterial pressure (AP) can be supported transiently by a Windkessel mechanism that increases cerebrovascular compliance (Ci). This defense mechanism exists in healthy participants during rapid standing and in patients during vasovagal syncope. However, it remains unknown whether the rise in Ci with falling AP exhibits a threshold effect. Thus, we tested the hypothesis that increased Ci is passive to a reduction in AP and starts to increase only after a threshold has been reached. To test this hypothesis, it was necessary to study a population that tolerates progressive large reductions in BP without a loss of consciousness. Therefore, we analyzed Ci changes during a graded head-up tilt (HUT) from patients with autonomic failure (AF). Methods: Finger AP and right middle cerebral artery blood velocity (MCAv) were recorded from 5 AF patients (n = 5 male, 61 ± 23 years, 25 ± 5 kg/m2) at supine rest and during graded-HUT (30, 45, 60 degrees). Tilt gradients increased incrementally every 5 minutes until AP reached a critically low value prompting termination of HUT. The total time in HUT was 11 ± 4 min. Individual AP and MCAv waveforms during supine rest and graded HUT (one waveform every 5 s) were assessed with a modified Windkessel model to calculate Ci and cerebrovascular resistance (CVR). Pulse pressure (PP) was calculated as systolic AP − diastolic AP. A threshold value for the increase in Ci was determined as five consecutive cardiac cycles greater than the average supine Ci plus 2 standard deviations. Results: Graded HUT resulted in an overall reduction in AP (85 ± 18 to 50 ± 7 mmHg), PP (72 ± 22 to 32 ± 19 mmHg), mean MCAv (62 ± 12 to 35 ± 7 cm/s), and CVR (1.4 ± 0.1 to 1.0 ± 0.3 mmHg/cm/s; all p &lt; 0.05 vs supine). Ci increased by 905 ± 756% (p = 0.04 vs supine). The threshold effect was evident as Ci began to increase progressively after PP fell by 15 ± 3 mmHg and AP fell by 12 ± 2 mmHg. Conclusions: Our results provide evidence that Ci increases after a threshold reduction in PP and AP in the apparent absence of autonomic support. These data support the idea that increasing Ci during reductions in AP represents a pressure-dependent Windkessel mechanism. Of interest, our findings provide clinical insight into how AF patients compensate for such large reductions in pressure without the assistance of CVR as a defense mechanism. NSERC USRA — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 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.

Rapid Changes in Cerebrovascular Compliance During Vasovagal Syncope

Background: The rapid reduction in arterial blood pressure (ABP) during vasovagal syncope (VVS) is associated with a characteristic decline in diastolic cerebral blood velocity (CBV) and maintained systolic CBV as measured by transcranial Doppler. This increased pulsatility was originally considered to be indicative of a “dysfunctional” increase in cerebrovascular resistance (CVR). Conversely, it may be due to increased cerebrovascular compliance (Ci) that partially attenuates the cerebral effects of rapid hypotension. We tested the hypothesis that Ci supports CBV during pre-syncope in VVS. Method: Finger ABP and right middle cerebral artery blood velocity (MCAv) were recorded from 15 otherwise healthy patients (n = 11 female, 40 ± 16 years, 24.9 ± 4.0 kg/m2) at rest and during head-up tilt (80°, 5 to 28 min). Individual ABP and CBV waveforms of every second heartbeat during VVS were input into a modified Windkessel model to calculate Ci and CVR. MCAv pulsatility was determined as pulse amplitude (systolic MCAv-diastolic MCAv) and Pulsatility Index (Pi; pulse amplitude/mean MCAv). Linear mixed models assessed the contribution of Ci to changes in CBV and Pi. Within-subject mediation analysis investigated the possibility of Ci mediating the relation between blood pressure (i.e., mean ABP and pulse pressure, PP) and cerebrovascular pulsatility. Results: Diastolic and systolic ABP decreased progressively during presyncope, resulting in a nadir reduction of mean ABP of Δ24 ± 9 mmHg at end-tilt (all p ≤ 0.04 vs mid-tilt). Mean MCAv decreased by 22 ± 12% prior to end-tilt (p &lt; 0.01 vs mid-tilt). CVR decreased progressively for 10s prior to end-tilt (p ≤ 0.04 vs mid-tilt). Pi increased significantly, with peak increases occurring at 4 s prior to end-tilt (77 ± 50%, p &lt; 0.01 vs mid-tilt). The increase in Ci (307 ± 223%, p &lt; 0.01 vs mid-tilt) significantly contributed to changes in MCAv (χ2 =10.6, p &lt; 0.01) and Pi (χ2 = 4.9, p = 0.03). Correlations of PP and ABP with Pi were not significant. However, PP was related to MCAv pulse amplitude (total effect: b = 1.57) and Ci ( b = -0.01, both p &lt; 0.01). Ci partially mediated (indirect effect: b = -0.78, p &lt; 0.01) the direct relation between PP and MCAv pulse amplitude ( b = 0.79, p = 0.01). Conclusion: These data provide evidence that Ci attenuates the fall in CBV under conditions of falling PP. Cerebrovascular regulation in VVS appears to be functioning as in healthy populations. However, this regulation is not suffcient to preserve flow in the presence of such extreme and rapid reductions in ABP. USRI — Western University, Natural Sciences and Engineering Research Council of Canada (NSERC, Grant No. RGPIN-2018-06255). This is the full abstract presented at the American Physiology Summit 2024 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.

DOSE-RESPONSE EFFECT OF SODIUM REDUCTION ON BLOOD PRSSURE IN TREATED HYPERTENSIVES: A SYSTEMATIC REVIEW AND INSTRUMENTAL VARIABLE META-ANALYSIS

Objective: To evaluate the dose-response effects of a reduction in dietary sodium intake on blood pressure (BP) in hypertensive individuals who were on antihypertensive treatments. The impact of antihypertensive-drug class was also examined. Design and method: We searched Medline (via Ovid), Embase, Scopus, Cochrane Central Register of Controlled Trials, and reference lists of relevant articles up to 12 November 2023. We included randomised controlled trials (RCTs) comparing the effect on BP between different levels of dietary sodium intake in adults who were diagnosed as primary hypertension and treated with constant antihypertensive medications during the study period. We excluded RCTs with duration &lt; 2 weeks. Dietary sodium intake was measured using 24-hour urinary sodium excretion. Instrumental variable meta-analyses were conducted to evaluate the dose-response effects of sodium reduction on BP. Subgroup analysis and multivariate meta-regression analysis were performed to examine the impact of antihypertensive-drug class. Results: 35 studies with 2885 participants were included. The pooled estimates of mean reduction in 24-hour urinary sodium excretion, systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) were 68.74 (95% confidence interval: 62.30-75.19) mmol, 4.33 (3.37-5.29) mmHg, 2.60 mm Hg (2.04-3.17), and 3.19 (2.50-3.87), respectively. For every 100 mmol reduction in 24-hour urinary sodium excretion, SBP, DBP, and MAP decreased by 6.81 (4.96-8.66) mmHg, 3.85 (2.26-5.43) mmHg, and 4.83 (3.22-6.44) mmHg, respectively (Fig 1). The observed dose-response effects differed across class of antihypertensive medication (P-diff = 0.084 for SBP, and P-diff&lt;0.05 for DBP and MAP). In Beta-blockers, Renin-Angiotensin-Aldosterone System (RAAS) inhibitors, and dual therapy groups, significant dose-response effects of sodium on SBP, DBP and MAP were observed. In Calcium Chanel Blockers (CCB) group, the dose-response relationship was only found for SBP. No dose-response effect on BP was observed in diuretics monotherapy group. Conclusions: Pooled evidence of RCTs suggests a dose-response relationship between sodium reduction and BP in treated hypertensives, which is impacted by class of antihypertensive medications.

Physiologic Validation of the Compensatory Reserve Metric Obtained From Pulse Oximetry Waveforms

Background: The compensatory reserve metric (CRM) provides a novel marker of hemodynamic status in prediction of sudden cardiovascular decompensation during central hypovolemia. The CRM has previously been calculated using arterial waveforms obtained from a photoplethysmographic volume-clamp technique. However, the in-field use of pulse oximetry is becoming more prominent in research and medicine. To improve in-field applicability of the CRM, this project aimed to validate pulse-oximetry derived CRM values relative to physiologic data during simulated hemorrhage through application of lower body negative pressure (LBNP). Methods: Forty-nine healthy adults (25 females) underwent a graded LBNP protocol with the following 5-minute stages: -0, -15, -30, -45, -60, -70, -80, -90, and 100 mmHg, or until the onset of pre-syncopal symptoms (tolerance) was reached. Arterial waveforms were sampled using pulse oximetry (Massimo Radical 7). The CRM was calculated using a validated one-dimensional convolutional neural network. A brachial artery catheter was used to measure intraarterial pressure. A 3-lead ECG was used to measure heart rate. SpO2 was measured using pulse oximetry. Cardiac output and stroke volume were estimated using the photoplethysmographic volume-clamp. Data were binned for the last thirty seconds of each completed stage, and at tolerance. Fixed-effect linear mixed models with repeated measures were used to examine the association between CRM values and physiologic variables. A priori significance was set at P&lt;0.05. Results: The median LBNP stage reached was 70 mmHg (Range: 45-100 mmHg). Relative to baseline, at tolerance there was a 50±12% ( P&lt;0.001) mean reduction in stroke volume, 65±27% ( P&lt;0.001) increase in heart rate, 18±8% ( P&lt;0.001) reduction in mean arterial pressure, 21±7% ( P&lt;0.001) systolic blood pressure, 8±9% ( P&lt;0.001) diastolic blood pressure, and 39±12% ( P&lt;0.001) pulse pressure. The CRM obtained using pulse oximetry was significantly associated with a reduction in stroke volume ( P&lt;0.001), increase in heart rate ( P&lt;0.001), and reductions in systolic ( P=0.033), diastolic ( P=0.036), and pulse pressure ( P=0.002). There was no statistically significant association between CRM and cardiac output ( P=0.421), SpO2 ( P=0.408), or mean arterial pressure ( P=0.214). Conclusion: The CRM obtained using pulse oximetry may be a valid, reliable marker of hemodynamic status with promising in-field applications. Future studies warrant investigation of feasibility and applicability within various contexts ranging from the operating room to the battlefield. The presented work was funded in part by the Congressionally Directed Medical Research Program (Award No. DM180240) and Offce of Naval Research (Awards No. N00014-18-D-7001 and N00014-19-C-2017). This is the full abstract presented at the American Physiology Summit 2024 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.