Arterial Pressure Responses Research Articles

Blood Pressure and Heart Rate Response to Orthostasis in Somali Americans.

Purpose: Cardiovascular health disparities are present in African Americans, but it remains unknown whether this phenomenon affect Somali Americans. Study of Somali Americans is warranted due to distinct genetic and cultural differences from African Americans of western African ancestry. Orthostatic hemodynamic responses have implications for cardiovascular risk, especially among African American females. We sought to examine race and sex differences in systolic (SAP) and diastolic (DAP) arterial pressure and heart rate (HR) responsiveness to standing. We hypothesized that SAP, DAP, and HR change from supine to standing position would be higher in Somali Americans. Methods: We studied blood pressure and HR responsiveness in 139 (70 Somali; age: 29±10 years, 69 White; age: 31±9 years) participants. Supine SAP, DAP, and HR were measured after at least five minutes of supine rest, and again after one minute of standing. SAP, DAP, and HR change was compared between groups. Results: ΔSAP and ΔDAP were similar between groups (race × sex: p>0.05). However, HR responsiveness to orthostasis varied between race and sex comparisons (race×sex: p=0.011). Somali females exhibited an augmented HR response to orthostasis compared to White females (Δ19±13 vs. 11±9 beats/min, p=0.005) and Somali males (Δ19±13 vs. 12±9 beats/min, p=0.020). Conclusion: ΔHR to standing is augmented in young female Somali Americans. These findings highlight an early potential impairment in hemodynamic regulation that may heighten future cardiovascular risk. Further work is warranted to identify the potential autonomic nervous system underpinnings that may contribute to potentiated orthostatic responses and cardiovascular risk in Somali American females. Clinical Trial Registration: www.clinicaltrials.gov; unique identifier, NCT04124848; NCT05411029; NCT03308578.

Angiotensin II for Catecholamine Resistant Vasodilatory Shock in Patients with Acute Kidney Injury: A Post-Hoc Analysis of the ATHOS-3 Trial

Abstract Objective The combination of catecholamine-resistant vasodilatory shock and acute kidney injury (AKI) is associated with high morbidity and mortality. The role of angiotensin II (ANGII) in this setting is unclear. Methods We conducted a post hoc analysis of the Angiotensin II for the Treatment of High-Output Shock (ATHOS) -3 trial which assessed the effect of Intravenous ANG II or placebo in patients with refractory vasodilatory shock in 75 intensive care units across nine countries in North America, Australasia, and Europe. We included patients with all stages AKI at initiation of ANG II or placebo and assessed 28-day mortality as primary outcome. We studied mean arterial pressure (MAP) response and days alive and free from renal replacement therapy (RRT) up to day seven as secondary outcome. Results Of 321 ATHOS-3 patients, 203 (63%) had AKI at randomization, with stage 3 AKI being dominant (67%). Median age was 63 years and median APACHE II score was 30. By day 28, overall, 118 (58%) of patients had died (53% with ANGII vs. 63% with placebo, HR = 0.75, 95% CI [0.52-1.08], p = 0.121). Among AKI stage 3 patients, however, ANGII was associated with significantly lower mortality (48% vs. 67%, HR = 0.57, 95% CI [0.36-0.91], p = 0.024). Additionally, in this subgroup, compared with placebo, patients receiving ANGII were more likely to achieve a MAP response (p < 0.001) and had more days alive and free from RRT (p < 0.001). Conclusions Compared with placebo, in patients with catecholamine-resistant vasodilatory shock and stage 3 AKI, ANGII is associated with lower 28-day, greater likelihood of MAP response, and more days alive and free from RRT. These findings support the conduct of future ANGII trials in patients with stage 3 AKI.

Sex-based differences in the blood pressure responses to muscle metaboreflex activation are consistent between limb and respiratory muscle.

The purpose of this study was to compare sex-based differences in the mean arterial blood pressure (MAP) response to limb and inspiratory metaboreflex activation, during relative and absolute workloads. Healthy males (M; n=9) and females (F; n=8) completed pulmonary function testing, forearm volume and circumference measurements, and bouts of limb and inspiratory muscle exercise. The exercises performed included bouts of rhythmic handgrip exercise (RHG) and inspiratory pressure threshold loading (PTL) to task failure, performed in a randomized order, and separated by 30 minutes of rest. Participants performed both RHG and PTL at predetermined relative (R) and absolute (A) workloads while cardiopulmonary measurements were recorded continuously. A time-dependent rise in MAP was observed in all participants, regardless of sex, muscle, or workload (p<0.001). MAP was greater in males than females during all exercise bouts regardless of muscle group or workload (p<0.001). The change in MAP from baseline was also greater in males (R-RHG: ∆31±12 mmHg; R-PTL: ∆31±9; A-RHG: ∆35±6; A-PTL: ∆30±7) than females (R-RHG: ∆21±7 mmHg; R-PTL: ∆13±7; A-RHG: ∆21±7; A-PTL: ∆14±3) (p<0.001). Results from this study show that when the forearm and diaphragm perform the same relative or absolute work, the blood pressure response is statistically similar, and both responses are greater in males than females. The findings from the present study suggest that the sex-based difference in the response to metaboreflex activation is similar between the limb and respiratory musculature.

Impaired Peripheral Vascular Function Following Ischemic Stroke in Mice: Potential Insights into Blood Pressure Variations in the Post-Stroke Patient.

High systolic blood pressure and increased blood pressure variability after the onset of ischemic stroke are associated with poor clinical outcomes. One of the key determinants of blood pressure is arteriolar size, determined by vascular smooth muscle tone and vasodilatory and vasoconstrictor substances that are released by the endothelium. The aim of this study is to outline alterations in vasomotor function in isolated peripheral arteries following ischemic stroke. The reactivity of thoracic aortic segments from male C57BL/6 mice to dilators and constrictors was quantified using wire myography. Acetylcholine-induced endothelium-dependent vasodilation was impaired after ischemic stroke (LogIC50 Sham = -7.499, LogIC50 Stroke = -7.350, p = 0.0132, n = 19, 31 respectively). The vasodilatory responses to SNP were identical in the isolated aortas in the sham and stroke groups. Phenylephrine-induced vasoconstriction was impaired in the aortas isolated from the stroke animals in comparison to their sham treatment counterparts (Sham LogEC50= -6.652 vs. Stroke LogEC50 = -6.475, p < 0.001). Our study demonstrates that 24 h post-ischemic stroke, peripheral vascular responses are impaired in remote arteries. The aortas from the stroke animals exhibited reduced vasoconstrictor and endothelium-dependent vasodilator responses, while the endothelium-independent vasodilatory responses were preserved. Since both the vasodilatory and vasoconstrictor responses of peripheral arteries are impaired following ischemic stroke, our findings might explain increased blood pressure variability following ischemic stroke.

Activation of nociception-sensitive ionotropic glutamate receptor-expressing rostroventrolateral medulla neurons by stimulation of cardiac afferents in rats.

Myocardial ischemia causes the release of bradykinin, which activates afferent nerve endings in the ventricular epicardium. This elicits a sympathetically mediated increase in arterial pressure and heart rate, referred to as the cardiogenic sympathetic afferent reflex. The rostroventrolateral medulla (RVLM) is a key sympathetic brain stem site for regulating cardiovascular activity. This study aimed to determine the importance of non-barosensitive nociception sympathetic activity and the role of glutamate receptor activation of RVLM neurons in the cardiogenic sympathetic afferent reflex. We tested the hypothesis that inhibition of barosensitive sympathetic activity attenuates but does not abolish the reflex response to cardiac visceral afferents. Renal sympathetic nerve activity (RSNA), arterial pressure, and heart rate responses to epicardial bradykinin application were recorded in anesthetized rats before and after bilateral RVLM microinjection of either GABAA agonist muscimol, ionotropic glutamate receptor antagonist kynurenic acid, N-methyl-d-aspartate (NMDA) receptor antagonist 2-amino-5- phosphonopentanoic acid (AP5), or non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Baroreceptor loading-induced inhibition of barosensitive activity attenuated the bradykinin-induced RSNA response (93 ± 14% increase) and tachycardia (18 ± 3 bpm). While RVLM muscimol microinjection abolished the RSNA response (1.6 ± 4.2% from baseline, 0.49 ± 0.38 μV*s), surprisingly, it did not abolish the tachycardia (27 ± 4 bpm). Kynurenic acid microinjection blocked the arterial pressure and RSNA responses, while AP5 or CNQX only attenuated the responses. These data suggest that nociception-sensitive sympathetic activity that does not appear to be barosensitive is also involved in the cardiogenic sympathetic afferent reflex. Importantly, while muscimol and kynurenic acid abolished the arterial pressure and RSNA response, neither affected the tachycardia, suggesting an alternate cardiac pathway independent of RVLM.

The Effect of Angiotensin II Type 1 Receptor Antagonist on Age-Related Differences in Renal Vascular Responses to Angiotensin II in Male and Female Rats.

Advancing age could influence renin angiotensin system components, especially angiotensin type 1 receptor (AT1R). This study examined the effect of AT1R antagonist, losartan, on age-related differences in renal vascular responses to angiotensin II in male and female rats. Forty-eight anesthetized male and female rats (8-12 and 24-28 weeks age ranges) were subjected to catheterize. Then, the responses of mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) to angiotensin II with or without losartan were determined and evaluated. There were not significant differences in the basal values of MAP, RPP, RBF, and RVR in males. However, it was observed significant difference in RVR in females (P < 0.05). The blockade of AT1R attenuated basal MAP and RPP in all the groups (P < 0.05). The infusion of losartan altered basal RVR and RBF values in female groups (P < 0.05). Moreover, losartan eliminated vasoconstrictor responses to angiotensin II in female groups (P < 0.05). Also, losartan induced significant vascular responses to angiotensin II in male groups (P < 0.05). Losartan could maintain RBF changes in response to angiotensin II in both 8-12- and 24-28-week females. Losartan enhanced the RBF response to angiotensin II in 8-12-week males, but not in 24-28-week males. It seems that females (not males) in various age ranges are resistance against RBF changes by acutely increased angiotensin II.

Respiratory modulation of sympathetic transduction to blood pressure in health and type 2 diabetes.

Type 2 diabetes (T2D) is often accompanied by hypertension, exaggerated blood pressure (BP) responses to sympatho-excitatory stressors, and raised cardiovascular disease risk. Appropriate respiratory-sympathetic coupling and sympathetic transduction to BP are important for short- and longer-term BP control. We tested the hypotheses that respiratory modulation of muscle sympathetic nerve activity (MSNA) and its transduction to BP would be impaired in T2D and associated with higher BP and respiratory-coupled BP variability. Resting MSNA, respiration and beat-to-beat BP were recorded in 20 T2D (49.1 ± 7.4 years; mean ± SD) and 13 healthy control (46.3 ± 9.4 years) participants. MSNA and the transduction of sympathetic bursts (signal-averaging) to mean arterial pressure (MAP) were compared at low and high lung volume phases. The peak MAP response following a sympathetic burst was lower during the high lung volume than low lung volume phase in controls (P = 0.005), whereas it was unchanged with phase in T2D participants (P = 0.522). Respiratory modulation of MSNA was impaired in T2D participants, who had an attenuated reduction in burst incidence from low to the high lung volume phase, versus controls (27.8 ± 38.4% vs. 49.4 ± 24.6%, respectively; P = 0.043). The T2D participants were grouped into unimpaired respiratory modulators (burst incidence modulation median or above) or impaired respiratory modulators (below median). Impaired modulators had higher systolic BP (133 ± 14 vs. 121 ± 11mmHg, P = 0.046), greater Traube-Hering wave amplitudes (6.3 ± 2.4 vs. 4.6 ± 1.1mmHg; P = 0.028) and higher BP variability (MAP average real variability, 2.0 ± 0.7 vs. 1.4 ± 0.3, P = 0.033). Respiratory modulation of MSNA and sympathetic transduction to BP are altered in T2D patients and may contribute to their increased hypertension and cardiovascular risk. KEY POINTS: Respiratory-sympathetic coupling and sympathetic transduction to blood pressure (BP) contribute to short- and longer-term BP control. Our understanding of these processes in health and type 2 diabetes (T2D), a condition with high prevalence of hypertension and cardiovascular risk, is incomplete. We found that respiration and sympathetic transduction to BP are coupled in healthy individuals. The mean arterial pressure response to a sympathetic burst was reduced during the high lung volume compared to the low lung volume phase. This coupling was absent in T2D. Respiratory modulation of muscle sympathetic nerve activity (MSNA) is impaired in T2D, with a blunted reduction of MSNA observed during the high lung volume phase. T2D patients with impaired respiratory MSNA modulation had augmented systolic BP, respiratory-related BP excursions (Traube-Hering waves) and BP variability. Abnormal respiratory modulation of MSNA and sympathetic transduction to BP in T2D may contribute to altered blood pressure control and cardiovascular risk in this population.

Effect of zamicastat on blood pressure and heart rate response to cold pressor test: A double-blind, randomized, placebo-controlled study in healthy subjects.

Dopamine beta-hydroxylase (DβH) inhibitors, like zamicastat, hold promise for treating pulmonary arterial hypertension. This study aimed to validate the mechanism of action of zamicastat by studying its effect on the overdrive of the sympathetic nervous system (SNS). A single-centre, prospective, double-blind, randomized, placebo-controlled, crossover study evaluated the effect of 400 mg zamicastat in 22 healthy male subjects. Cold pressor test (CPT) was performed at screening and each treatment period on Days -1 and 10. Plasma and 24 h-urine levels of dopamine (DA), epinephrine (EPI) and norepinephrine (NE), and plasma DβH activity, were measured. Compared to placebo, zamicastat showed a - 4.62 mmHg decrease in systolic blood pressure during the cold stimulus vs. rest phases on Day 10 of CPT (P = .020). Zamicastat decreased mean arterial pressure response to cold stimulus during CPT (-2.62 mmHg; P = .025). At Day 10, zamicastat significantly increased plasma DA, before CPT (12.63 ng/L; P = .040) and after CPT (19.22 ng/L; P = .001) as well as the estimated plasma EPI change from baseline after CPT (P = .040). Inhibition of plasma DβH activity ranged from 19.8% to 25.0%. At Day 10, significant reductions in 24-h urinary excretion of EPI (P = .002) and NE (P = .001) were observed. Zamicastat Cτ geometric mean ± GSD ranged from 45.86 ± 1.46 ng/mL on Day 3 to 58.64 ± 1.52 ng/mL on Day 10, with moderate inter-individual variability (CV: 32.6%-36.6%). Steady state was already achieved on Day 6. Our results demonstrated the effect of zamicastat on the overdrive sympathetic response to cold stimulus, confirming its potential as SNS modulator.

Reflex sympathetic activation to inspiratory muscle loading is attenuated in females relative to males.

Intense inspiratory muscle work can evoke a metabolite-stimulated pressor reflex, commonly referred to as the respiratory muscle metaboreflex. When completing similar relative and absolute levels of inspiratory work, females have an attenuated blood pressure response. We sought to test the hypothesis that the lower blood pressure response to the respiratory muscle metaboreflex in females is associated with a reduced sympathetic response. Healthy young (26 ± 4 yr) males (n = 9) and females (n = 7) completed two experimental days. On day 1, participants completed pulmonary function testing and became familiarized with an inspiratory pressure-threshold loading (PTL) task. On the second day, balloon-tipped catheters were placed in the esophagus and stomach to measure pleural and gastric pressures, and transdiaphragmatic pressure was calculated. A microelectrode was inserted into the fibular nerve to quantify muscle sympathetic nerve activity (MSNA), and participants then completed isocapnic PTL to task failure. There was a significant sex-by-time interaction in the mean arterial pressure (MAP, P = 0.015) and burst frequency (P = 0.039) response to PTL. Males had a greater rise in MAP (Δ21 ± 9 mmHg) than females (Δ13 ± 5 mmHg, P = 0.026). Males also demonstrated a greater rise in MSNA burst frequency (Δ18 ± 7 bursts/min) than females (Δ10 ± 5 bursts/min, P = 0.015). The effect of sex was observed despite females and males completing the same magnitude of diaphragm work throughout the task (P = 0.755). Our findings provide novel evidence that the lower blood pressure response to similar relative and absolute inspiratory muscle work in females is associated with lower sympathetic activation.NEW & NOTEWORTHY The blood pressure response to high levels of inspiratory muscle work is lower in females and occurs alongside a reduced sympathetic response. The reduced blood pressure and sympathetic response occur despite males and females performing similar levels of absolute inspiratory work. Our findings provide evidence that sex differences in the respiratory muscle metaboreflex are, in part, sympathetically mediated.

Re-evaluating the Need for Routine Maximal Aerobic Capacity Testing within Fighter Pilots.

INTRODUCTION: There is a current belief in aviation suggesting that aerobic training may reduce G-tolerance due to potential negative impacts on arterial pressure response. Studies indicate that increasing maximal aerobic capacity (<mml:math id="ie1" display="inline"><mml:mrow><mml:mover><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math>o₂ max) through aerobic training does not hinder G-tolerance. Moreover, sustained centrifuge training programs revealed no instances where excessive aerobic exercise compromised a trainee's ability to complete target profiles. The purpose of this review article is to examine the current research in the hope of establishing the need for routine <mml:math id="ie2" display="inline"><mml:mrow><mml:mover><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math>o₂-max testing in air force pilot protocols.METHODS: A systematic search of electronic databases including Google Scholar, PubMed, the Aerospace Medical Association, and Military Medicine was conducted. Keywords related to "human performance," "Air Force fighter pilots," "aerobic function," and "maximal aerobic capacity" were used in various combinations. Articles addressing exercise physiology, G-tolerance, physical training, and fighter pilot maneuvers related to human performance were considered. No primary data collection involving human subjects was conducted; therefore, ethical approval was not required.RESULTS: The <mml:math id="ie3" display="inline"><mml:mrow><mml:mover><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math>o₂-max test provides essential information regarding a pilot's ability to handle increased Gz-load. It assists in predicting G-induced loss of consciousness by assessing anti-G straining maneuver performance and heart rate variables during increased G-load.DISCUSSION: <mml:math id="ie4" display="inline"><mml:mrow><mml:mover><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math>o₂-max testing guides tailored exercise plans, optimizes cardiovascular health, and disproves the notion that aerobic training hampers G-tolerance. Its inclusion in air force protocols could boost readiness, reduce health risks, and refine training for fighter pilots' safety and performance. This evidence-backed approach supports integrating <mml:math id="ie5" display="inline"><mml:mrow><mml:mover><mml:mtext>V</mml:mtext><mml:mo>˙</mml:mo></mml:mover></mml:mrow></mml:math>o₂-max testing for insights into fitness, risks, and tailored exercise.Zeigler Z, Acevedo AM. Re-evaluating the need for routine maximal aerobic capacity testing within fighter pilots. Aerosp Med Hum Perform. 2024; 95(5):273-277.

Enhancing Endothelial Function with Nutrient-Enriched Table Hen Eggs: A Randomized Study in Patients Recovering from Acute Coronary Syndrome.

This study investigated the effect of consumption of table eggs enriched with n-3 polyunsaturated fatty acids (n-3 PUFA), lutein, vitamin E and selenium on microvascular function, oxidative stress and inflammatory mediators in patients after acute coronary syndrome (ACS). In a prospective, randomized, interventional, double-blind clinical trial, ACS patients were assigned to either the Nutri4 (N=15, mean age: 57.2±9.2 years), or the Control group (N=13; mean age 56.8±9.6 years). The Nutri4 group consumed three enriched hen eggs daily for three weeks, providing approximately 1.785 mg of vitamin E, 0.330 mg of lutein, 0.054 mg of selenium and 438 mg of n-3 PUFAs. Biochemical parameters, including serum lipids, liver enzymes, nutrient concentrations, serum antioxidant enzyme activity (catalase (CAT), glutathione peroxidase (GPx), superoxide dismutase (SOD)), and markers of oxidative stress (thiobarbituric acid reactive substances (TBARS) and ferric reducing ability (FRAP)), were assessed before and after the dietary interventions. Additionally, arterial blood pressure, heart rate, body composition, fluid status, anthropometric measurements, and skin microvascular blood flow responses to various stimuli (postocclusive reactive hyperemia (PORH), acetylcholine- (AchID), and sodium nitroprusside- (SNPID)) were measured using laser Doppler flowmetry (LDF) throughout the study. The intake of Nutri4 eggs led to a significant reduction in LDL cholesterol levels, while the levels of total cholesterol remained within the established reference values. Consuming Nutri4 eggs resulted in a 12.7% increase in serum vitamin E levels, an 8.6% increase in selenium levels, and demonstrated a favorable impact on microvascular reactivity, as evidenced by markedly improved PORH and ACh ID. Nutri4 eggs exerted a significant influence on the activity of GPx and SOD, with no observed changes in TBARS or FRAP values. The consumption of Nutri4 eggs positively influenced microvascular function in individuals with ACS, without eliciting adverse effects on oxidative stress.

Beneficial Effect of Heat Treatment on the Exercise Pressor Reflex in Hindlimb Ischemia-Reperfusion: Potential Role of P2X3

PURPOSE: In peripheral artery disease (PAD), a greater blood pressure (BP) response during exercise causes cardiovascular and cerebrovascular risks. The exercise pressor reflex (EPR) is a key factor for why BP is exaggerated in PAD patients. Thus, we examined the effect of heat treatment (HT) with two temperature increments in skeletal muscle: 1.5 and 3oC on the EPR response following limb ischemia-reperfusion (IR) injury, one of the most common pathological conditions seen in PAD. In addition, the P2X3 (an ATP-sensitive receptor) in the muscle afferent dorsal root ganglion (DRG) was also evaluated. We hypothesized that IR upregulates the BP response to static muscle contraction and the protein expression of P2X3 in muscle afferent nerves. HT attenuates those exaggerated responses. METHODS: An experimental IR model was induced by 6 hours of ischemia followed by 18 hours of reperfusion in rats (IR rats). For HT groups, three HT sessions (muscle temperature increased by 1.5 or 3oC) for 30 mins/each time were applied. EPR response was evoked by static muscle contraction (30s). Protein expression of the P2X3 receptor in DRGs was examined. Data are presented as mean ± standard deviation. Results: The mean arterial pressure (MAP) response to the static muscle contraction was significantly exaggerated in rats of IR 18h (vs. Sham, P=0.018). With increasing Tm by 1.5°C, there was a promising trend that thus exaggerated BP response was attenuated (IR 18h + HT 1.5°C, n=5 vs. IR 18h rats, n=5, P=0.08). Meanwhile, the exaggerated BP response was significantly attenuated with the Tm increasing by 3°C (IR 18h + HT 3°C, n=5, vs. IR 18h rats, n=5, P=0.032). The expression of the P2X3 receptor was significantly enhanced in the DRGs of IR 18h rats (n=4, p&lt;0.01 vs. sham, n=6). The upregulated P2X3 was suppressed in the DRGs of IR 18h rats +HT of 1.5°C (n=3, p&lt;0.01 vs. IR 18h, n=4) and there was a promising trend that upregulated P2X3 was suppressed in the DRGs of IR 18h rats +HT of 3°C (n=3, P=0.079 vs. IR 18h, n=4). CONCLUSION: IR injury leads to upregulation of EPR response and this effect was attenuated by HT. The P2X3 signaling pathways are likely involved in the beneficial regulatory effect of HT on EPR in IR. Further data collection will be performed to test this conclusion. Supported by NIH R01 HL141198 &amp; HL164571; AHA GRANT # 940567/Lu Qin/2022; and College of Medicine DOM Innovation and Inspiration Award. The authors sincerely thank Chunying Yang for the excellent technical assistance. 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.

Divergent roles of purinergic 2X receptors in the pressor response to treadmill exercise in male and female rats

Our objective was to investigate the role played by ATP sensitive purinergic 2X (P2X) receptors in evoking the pressor response to treadmill running in male and female rats with and without simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2X receptor antagonist, 10 mg i.v.), would reduce the pressor and end-exercise plasma norepinephrine (NE) response to four minutes of treadmill exercise (15 m×min−1; 1° incline) in male and female rats with a greater magnitude of effect in rats with simulated PAD compared to sham-operated rats. Methods: Ten rats had both femoral arteries ligated ~72 hours prior to experimental protocols. Fourteen rats had sham procedures performed in which the femoral arteries were exposed, and 5-0 suture was passed under the arteries but not tied. These groups are referred to as “ligated” and “sham”, respectively. In all rats, the right carotid artery was cannulated (PE-25) for blood pressure measurement and arterial blood samples and the right jugular vein was cannulated (PE-25) for administration of PPADS. After the rats recovered (~2 hrs), treadmill exercise was initiated (15 m·min−1, 1° incline) and the rat completed a four minute exercise bout. While the rat was still running, an arterial blood sample (~100 μl) was drawn for plasma NE assessment. Following a 20 minute rest, PPADS (10 mg, dissolved in 0.2 mL saline) was infused into the jugular vein over 10 min. After PPADS infusion, a second treadmill exercise bout and blood collection were performed as described for the control condition. The pressor and plasma NE responses to submaximal treadmill running before and after the injection of PPADS (10 mg) were compared. Data are expressed as mean ± SD. Statistical significance was defined as P≤0.05. Results: In male rats, PPADS significantly reduced the mean arterial pressure (MAP) response to exercise in both sham ( n=6, Peak ΔMAP control: 19±6; PPADS: 11±9 mmHg; P=0.033) and ligated rats ( n=4; control: 24±3 mmHg; PPADS: 16±6 mmHg; P=0.021) with a similar magnitude of effect observed between groups (p=0.544). In female rats, PPADS had no effect on the MAP response to exercise in either sham (n=6, 13±8; PPADS: 10±5 mmHg; P=0.171) or ligated (n=6, 17±5; PPADS: 18±6 mmHg; P=0.375) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced end-exercise plasma NE concentration in both male (n=11, 200±131; PPADS: 139±61 pg/mL; P=0.016) and female (n=10, 199±133; PPADS: 140±101 pg/mL; P=0.027) rats. Conclusions: The data indicate that P2X receptors contribute to the sympathetic response to exercise in both male and female sham and ligated rats, but that sympathoexcitatory roles for P2X receptors translates into an obligatory role in the blood pressure response to treadmill exercise in male but not female rats. National Institutes of Health R01HL161160. 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.

Postoperative orthostatic intolerance following fast-track unicompartmental knee arthroplasty: incidence and hemodynamics—a prospective observational cohort study

BackgroundEarly postoperative mobilization is essential for early functional recovery but can be inhibited by postoperative orthostatic intolerance (OI). Postoperative OI is common after major surgery, such as total knee arthroplasty (TKA). However, limited data are available after less extensive surgery, such as unicompartmental knee arthroplasty (UKA). We, therefore, investigated the incidence of OI as well as cardiovascular and tissue oxygenation responses during early mobilization after UKA.MethodsThis prospective single-centre observational study included 32 patients undergoing primary UKA. Incidence of OI and cardiovascular and tissue oxygenation responses during mobilization were evaluated preoperatively, at 6 and 24 h after surgery. Perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain during mobilization and opioid usage were recorded.ResultsDuring mobilization at 6 h after surgery, 4 (14%, 95%CI 4–33%) patients experienced OI; however, no patients terminated the mobilization procedure prematurely. Dizziness and feeling of heat were the most common symptoms. OI was associated with attenuated systolic and mean arterial blood pressure responses in the sitting position (all p < 0.05). At 24 h after surgery, 24 (75%) patients had already been discharged, including three of the four patients with early OI. Only five patients were available for measurements, two of whom experienced OI; one terminated the mobilization procedure due to intolerable symptoms. We observed no statistically significant differences in perioperative fluid balance, bleeding, surgery duration, postoperative hemoglobin, pain, or opioid usage between orthostatic intolerant and tolerant patients.ConclusionsThe incidence of orthostatic intolerance after fast-track unicompartmental knee arthroplasty is low (~ 15%) and is associated with decreased orthostatic pressure responses. Compared to the previously described orthostatic intolerance incidence of ~ 40% following total knee arthroplasty, early orthostatic intolerance is uncommon after unicompartmental knee arthroplasty, suggesting a procedure-specific component.Trial registration: Prospectively registered at ClinicalTrials.gov; registration number: NCT04195360, registration date: 13.12.2019.

Sex differences in the purinergic 2 receptor-mediated blood pressure response to treadmill exercise in rats with simulated peripheral artery disease.

We investigated the role played by ATP-sensitive purinergic 2 (P2) receptors in evoking the pressor response to treadmill exercise in male and female rats with and without femoral arteries that were ligated for ∼72 h to induce simulated peripheral artery disease (PAD). We hypothesized that PPADS (P2 receptor antagonist, 10 mg iv) would reduce the pressor response to 4 min of treadmill exercise (15 m·min-1, 1° incline) and steady-state exercise plasma norepinephrine (NE) values in male and female rats, and that the magnitude of effect of PPADS would be greater in rats with simulated PAD ("ligated") than in sham-operated rats. In males, PPADS significantly reduced the difference between steady-state exercise and baseline mean arterial pressure (ΔMAP) response to treadmill exercise in sham (n = 8; pre-PPADS: 12 ± 2, post-PPADS: 1 ± 5 mmHg; P = 0.037) and ligated (n = 4; pre-PPADS: 20 ± 2, post-PPADS: 11 ± 3 mmHg; P = 0.028) rats with a similar magnitude of effect observed between groups (P = 0.720). In females, PPADS had no effect on the ΔMAP response to treadmill exercise in sham (n = 6; pre-PPADS: 9 ± 2, post-PPADS: 7 ± 2 mmHg; P = 0.448) or ligated (n = 6; pre-PPADS: 15 ± 2, post-PPADS: 16 ± 3 mmHg; P = 0.684) rats. When NE values were grouped by sex independent of ligation/sham status, PPADS significantly reduced plasma NE in male (P = 0.016) and female (P = 0.027) rats. The data indicate that P2 receptors contribute to the sympathetic response to exercise in both male and female rats but that the sympathoexcitatory role for P2 receptors translates into an obligatory role in the blood pressure response to exercise in male but not in female rats.NEW & NOTEWORTHY Here, we demonstrate that purinergic 2 (P2) receptors contribute significantly to the blood pressure response to treadmill exercise in male rats both with and without simulated PAD induced by femoral artery ligation. We found no role for P2 receptors in the blood pressure response to treadmill exercise in female rats, thus revealing clear sex differences in P2 receptor-mediated blood pressure control during exercise.

Expansion of Psychosocial Distress in Nurses Working in Hemodialysis During Exposure to COVID-19 Pandemic in Bulgaria

Abstract A new type of virus, SARS-CoV-2, has spread globally throughout the world. The COVID-19 epidemic rapidly spread worldwide. The health care system, society and medical professionals have prepared to adapt, train and resist the increased psychosocial pressure. In this situation, the role and place of medical professionals has become noticeably more prominent, and the psychosocial stress of the work environment has increased its impact – progressing to high levels of harmful intensity towards the medical professionals. Focusing within the borders of Bulgaria, it can be argued that the initial two waves of high levels of COVID-19 prevalence were difficult and critical to overcome. The aim of our study is to investigate the impact of psychosocial stress on the functional status examined with the response of arterial blood pressure of nurses, practicing long-term care in hemodialysis clinics and centers during exposure to COVID-19 pandemic. A study was conducted on the subjective assessment of psychological and social risk factors, and arterial systolic and diastolic blood pressure in 2018-2019 (pre-COVID-19 period) and 2020 (COVID-19 period), respectively. The methods used were the NIOSH questionnaire – to assess psychosocial stress at work and to measure blood pressure with a sphygmomanometer. The results showed that the expansion of psychosocial risks from the work environment impacted on the functional status of nurses, with an increase in the level of social support and systolic blood pressure during the COVID-19 compared to the pre-COVID-19 period, and a decrease in the level of control when comparing the same periods. We will monitor and observe these effects with concern in order to respond in a timely manner with effective and practical strategies, policies and programs to counter and prevent psychosocial stress in the workplace. One of the outlined guiding goals and trends for this will be to both preserve and prolong the work life of nurses and to reposition them as a key and significant group for the healthcare system.

Dynamic arterial elastance as a predictor of arterial pressure response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome-a systematic review and meta-analysis.

During the de-escalation phase of circulatory shock, norepinephrine weaning may induce diverse arterial pressure responses in patients with different vasomotor tones. Dynamic arterial elastance (Eadyn) has been extensively studied to predict the arterial pressure response to interventions. We conducted this meta-analysis to systematically assess the predictive performance of Eadyn for the mean arterial pressure (MAP) response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. A systematic literature search was conducted on May 29, 2023 (updated on January 21, 2024), to identify relevant studies from electronic databases. The area under the hierarchical summary receiver operating characteristic curve (AUHSROC) was estimated as the primary measure of diagnostic accuracy because of the varied thresholds reported. Additionally, we observed the distribution of the cutoff values of Eadyn, while computing the optimal value and its corresponding 95% confidential interval (CI). A total of 5 prospective studies met eligibility, comprising 183 participants, of whom 67 (37%) were MAP responders. Eadyn possessed an excellent ability to predict the MAP response to norepinephrine weaning in patients with vasoplegic syndrome, with an AUHSROC of 0.93 (95% CI: 0.91-0.95), a pooled sensitivity of 0.94 (95% CI: 0.85-0.98), a pooled specificity of 0.73 (95% CI: 0.65-0.81), and a pooled diagnostic odds ratio of 32.4 (95% CI: 11.7-89.9). The cutoff values of Eadyn presented a nearly conically symmetrical distribution; the mean and median cutoff values were 0.89 (95% CI: 0.80-0.98) and 0.90 (95% CI: not estimable), respectively. This meta-analysis with limited evidences demonstrates that Eadyn may be a reliable predictor of the MAP response to norepinephrine weaning in mechanically ventilated patients with vasoplegic syndrome. PROSPERO CRD42023430362.

Amplified P2X3 pathway activity in muscle afferent dorsal root ganglion neurons and exercise pressor reflex regulation in hindlimb ischaemia-reperfusion.

Hindlimb ischaemia-reperfusion (IR) is among the most prominent pathophysiological conditions observed in peripheral artery disease (PAD). An exaggerated arterial blood pressure (BP) response during exercise is associated with an elevated risk of cardiovascular events in individuals with PAD. However, the precise mechanisms leading to this exaggerated BP response are poorly elucidated. The P2X3 signalling pathway, which plays a key role in modifying the exercise pressor reflex (EPR), is the focus of the present study. We determined the regulatory role of P2X3 on the EPR in a rat model of hindlimb IR. In vivo and in vitro approaches were used to determine the expression and functions of P2X3 in muscle afferent nerves and EPR in IR rats. We found that in IR rats there was (1) upregulation of P2X3 protein expression in the L4-6 dorsal root ganglia (DRG); (2) amplified P2X currents in isolated isolectin B4 (IB4)-positive muscle DRG neurons; and (3) amplification of the P2X-mediated BP response. We further verified that both A-317491 and siRNA knockdown of P2X3 significantly decreased the activity of P2X currents in isolated muscle DRG neurons. Moreover, inhibition of muscle afferents' P2X3 receptor using A-317491 was observed to alleviate the exaggerated BP response induced by static muscle contraction and P2X-induced BP response by α,β-methylene ATP injection. P2X3 signalling pathway activity is amplified in muscle afferent DRG neurons in regulating the EPR following hindlimb IR.

Interaction between Nuclear Receptor and Alpha-Adrenergic Agonist Subtypes in Metabolism and Systemic Hemodynamics of Spontaneously Hypertensive Rats.

Partial and full PPAR-γ agonists have shown promising effects and antihypertensive and antidiabetic agents through increased plasma adiponectin concentration. This study is aimed at examining the role of PPAR-γ, alpha-adrenoceptors, and adiponectin receptors in the modulation of vasopressor responses to angiotensin II (Ang II) and adrenergic agonists, after a subset treatment of partial and full PPAR-γ agonists, each individually, and also when coupled with adiponectin in SHRs. The antioxidant potential and metabolic indices for these animals were also determined. Group I (WKY) and group II (SHR) were designated as normotensive control and hypertensive control, respectively. Groups III (SHR) and IV (SHR) received irbesartan (30 mg/kg) and pioglitazone (10 mg/kg) orally for 28 days, and groups V (SHR), VI (SHR), and VII (SHR) were treated with adiponectin (2.5 μg/kg) intraperitoneally alone, in combination with irbesartan, and in combination with pioglitazone, respectively, from days 21 to 28 only. On day 29, sodium pentobarbitone (60 mg/kg) was used to anesthetize all test animals, and systemic hemodynamic and plasma adiponectin concentrations and in vitro and in vivo antioxidant potential were measured. As compared to the WKY control, the SHR control group's noninvasive blood pressure and basal mean arterial pressure were significantly greater, along with increased arterial stiffness, lower plasma nitric oxide, adiponectin concentration, and antioxidant enzyme levels (all P < 0.05). However, they were gradually normalized by single drug treatments in all groups, and to a greater extent in the SHR + Irb + Adp group (P < 0.05). In the acute study, the dose dependant mean arterial pressure responses to intravenously administered adrenergic agonists and angiotensin-II were significantly larger in SHRs as compared to WKY by 20-25%. Adiponectin alone and in combination significantly blunted vasopressor responses to these alpha-adrenergic agonists in the SHR + Pio + Adp group by 63%, whereas attenuated responses to ANG-II administration to 70% in SHR + Irb + Adp. In conclusion, the combined treatment of adiponectin with PPAR-agonists reduced the systemic vascular responses to adrenergic agonists and improved arterial stiffness. This an evidence of the interaction of adiponectin receptors, PPAR-γ, alpha-adrenoceptors, and ANG-II in the systemic vasculature of SHRs. A significant level of synergism has also been proved among full PPAR-γ agonists and adiponectin receptors.

Abstract 12634: Amplified P2x 3 Pathway Activity in IB4 Positive Muscle DRG Neurons and Exercise Pressor Reflex Regulation in Hindlimb Ischemia-Reperfusion

Background: Hindlimb ischemia-reperfusion (IR) represents one of the most prominent pathological conditions observed in peripheral artery disease (PAD). Arterial blood pressure response (BP) during exercise, partly driven by the exaggerated exercise pressor reflex (EPR), is associated with an elevated risk of cardiovascular events in PAD patients. However, the precise underlying mechanisms leading to this exaggerated BP response are poorly elucidated. The purinergic P2X 3 signaling pathway, which plays a key role in modifying the EPR, was the focus of the present study. Objectives: To examine the regulatory role of P2X 3 on the EPR in a rat model of hindlimb IR, which was induced by 6 hours’ ischemia followed by 18 hours’ reperfusion (referred to as IR rats). Results: We found that, in IR rats, there were: 1) upregulation of P2X 3 protein expression in the L4-6 dorsal root ganglion (DRG) (1.48±0.16 in IR rats/n=8 vs. 1.00±0.41 in sham rats/n=9; P&lt;0.05), which was localized in IB4 positive DRG neurons by the method of immunohistochemistry, 2) amplified P2X currents in isolated muscle DRG neurons (P2X transient currents: 1281.64±776.74 pA in IR rats/n=25, vs. 717.91±556.2 pA in sham rats/n=9, P&lt;0.05; and sustain currents: 466.94±168.68 pA in IR rats/n=11, vs. 271.49±200.90 pA in sham rats/n=8, P&lt;0.05); 3) amplification of P2X-mediated BP response (29±8 mmHg in IR rats/n=12 vs. 21±4 mmHg in sham rats/n=7; P&lt;0.05); and 4) alleviation of the exaggerated BP response induced by static muscle contraction (18±8 mmHg in IR +A317491/n=8, vs. 29±11 mmHg in IR/n=7, P&lt;0.05) and P2X-mediated BP response by α, β-me-ATP injection (15±4 mmHg in IR+A317491 /n=6 vs. 23±7 mmHg in IR/n=4, P&lt;0.05) following the inhibition of muscle afferents’ P2X 3 receptor by A-317491. We further verified that both A-317491 and siRNA knockdown of P2X 3 significantly decreased the activity of P2X currents in the isolated muscle DRG neurons (all P&lt;0.05 vs. their respective controls). Conclusion: With the above evidence from multiple approaches, we concluded that the P2X 3 signaling pathway activity is amplified following hindlimb IR via the enhancing expression and activity of P2X 3 receptors in IB4 positive muscle DRG afferents. This contributes to the exacerbated EPR responses in PAD.