Heart Rate Responses Research Articles

The Contribution of Na+ or Cl− to Central NaCl−induced Cardiovascular Responses in Rodents

A high salt diet elevates plasma and cerebrospinal fluid NaCl concentrations in salt-sensitive hypertensive humans and animals. Acute or chronic intracerebroventricular (ICV) infusion of hypertonic NaCl elevates sympathetic nerve activity and blood pressure. However, it is unclear which ion, Na+ or Cl−, contributes to this response. The purpose of the present study was to investigate the extent to which acute increases in cerebrospinal fluid Na+ and Cl− increase ABP and HR in rodents. Male Sprague Dawley rats (n=6; body weight: 270-350 g) were anesthetized with isoflurane (2-3% in 100% O2) and instrumented with a lateral ventricle cannula for ICV infusions. Additionally, arterial and venous catheters were implanted to record BP and administer drugs, respectively. At least 4 days after recovery, ABP and HR were measured in response to ICV infusion (10uL over 10 min) of the following solutions: artificial cerebrospinal fluid (aCSF); 0.3 M and 0.6 M NaCl; 0.15 M and 0.3 M Na2SO4, and 0.3 M and 0.6 M NH4Cl. Each animal received one ICV infusion of each solution every other day. Data are presented as mean ± SE. Baseline ABP and HR did not differ across each ICV infusion (ABP: from 98 ± 6 mmHg to 106 ± 6 mmHg; and HR: from 337 ± 17 bpm to 363 ± 12 bpm). As expected, ICV infusion of 0.3 M and 0.6 M NaCl produced concentration-dependent increases in ABP (Δpeak ABP 0.3 M NaCl: 17 ± 2 mmHg; 0.6 M NaCl: 26 ± 3 mmHg). While ICV infusions of Na2SO4 at both concentrations also increased ABP, the magnitudes were reduced compared to NaCl (Δpeak ABP 0.15 M Na2SO4: 11 ± 2 mmHg; 0.3 M Na2SO4: 17 ± 3 mmHg). On the other hand, infusion of NH4Cl produced a modest increase in ABP (Δpeak ABP 0.3 M NH4Cl: 8 ± 2 mmHg and 0.6 M NH4Cl: 9 ± 3 mmHg). However, it did not differ from aCSF (Δpeak ABP aCSF: 6 ± 2 mmHg). HR responses induced by NaCl varied greatly (Δpeak HR 0.3 M NaCl: 15 ± 22 bpm; 0.6 M NaCl: 19 ± 17 bpm). In contrast, both concentrations of Na2SO4 consistently increased HR (Δpeak HR 0.15 M Na2SO4: 64±10 bpm; 0.3 M Na2SO4: 60±10 bpm). Additionally, ICV infusions of NH4Cl also tended to enhance HR (Δpeak HR 0.3 M NH4Cl: 38 ± 13 bpm and 0.6 M NH4Cl: 41 ± 23 bpm). To end, ICV infusion of aCSF increased HR by 18 ± 3 bpm. These results suggest that the NaCl−induced pressor response is largely attributed to Na+. However, Na+ alone cannot fully account for the NaCl−induced pressor response. NIH R01 HL163906, HL152680, HL145875. 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.

Central command activation during exercise is essential for the bradycardic response to diving

Mammalian diving response evokes complex cardiovascular adjustments, including bradycardia during sustained muscular activity. This is intriguing because voluntary exercise involves the activation of central command and skeletal muscle afferents, known to provoke tachycardia by reducing vagal outflow and increasing cardiac sympathetic activity. Nonetheless, it is currently unknown how diving-induced bradycardia can override the exercise tachycardia. Given this, we aimed to test the hypothesis that central and peripheral afferent mechanisms interact to modulate this physiological phenomenon. In three visits, 32 healthy subjects (15 women; 22±3 yr) were exposed to trigeminal nerve stimulation (i.e., facial cooling; TGS) to partially activate the diving reflex at rest (semi-recumbent position) and under three protocols: 1) during voluntary light (resting heart rate+20 beats.min−1) and moderate (resting heart rate+50 beats.min−1) steady-state cycling exercise; 2) during isolation of peripheral afferent reflexes via passive exercise (muscle mechanoreceptors) and cold pressor test (nociceptors; CPT), and; 3) during CPT with concurrent light exercise. The exercise intensities were assumed to provide different levels of central command activation, while both passive exercise and CPT were used to provide insights into the contribution of central command to diving bradycardia. TGS was performed for at least 90 seconds in all conditions. Beat-to-beat heart rate (HR, by electrocardiography) and blood pressure (finger photoplethysmography) were continuously measured, and surface electromyography was used to ensure the lack of volitional component during passive exercise. TGS elicited significant bradycardia at rest (Δ-12±0.9 beats·min−1; P<0.001), and this response was increased during voluntary light exercise (Δ-15±1.2 beats·min−1; P=0.002), but unaffected during voluntary moderate exercise when compared to rest (Δ-11±1.3 beats·min−1; P=0.536). In contrast, compared to rest, the HR response to TGS during passive exercise was significantly attenuated (Δ-13±1.2 beats·min−1 vs. Δ-9±1.7 beats·min−1; P=0.039), whereas CPT completely abolish the diving bradycardic response (Δ0±1.6 beats·min−1; P<0.001). However, when the volitional component was restored during CPT with concurrent light exercise, TGS provoked a significant bradycardic response, when compared to CPT condition (Δ1±1.6 beats·min−1 vs. Δ-10±2.1 beats·min−1; P=0.004). Notably, our findings were not affected by sex. In conclusion, these findings suggest that 1) central command activation during cycling exercise is essential for the bradycardic response to diving; 2) isolated peripheral afferent reflexes exert inhibitory feedback to modulate diving-induced bradycardia, and; 3) central and peripheral afferent feedback are important mechanisms by which exercise modulates the dive response. CNPq 307764/2022-2; CAPES (001). 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.

The efficacy of articaine in pain management during endodontic procedures in pediatric patients

ObjectiveThis trial aimed to study the efficacy of articaine in pain management during endodontic procedures in pediatric patients.MethodsNinety-eight children who received endodontic painless treatment were collected and randomly divided into the control group and observation group, with 49 cases in each group. The control group received infiltration anesthesia with lidocaine, and the observation group received infiltration anesthesia with articaine. Anesthesia effect, anesthesia onset time, sensory recovery time, duration of anesthesia, pain intensity, blood pressure, heart rate, and adverse reactions were compared.ResultsThe effective rate of anesthesia in the observation group was higher than that in the control group. The anesthesia onset time and sensory recovery time were shorter, the duration of anesthesia was longer, and the VAS score and facial expression score were lower in the observation group than in the control group. The heart rate of the observation group was lower, and diastolic blood pressure was higher than those of the control group. The total incidence of adverse reactions in the observation group was lower than that in the control group.ConclusionIn the treatment of dental pulp diseases in children, the use of articaine can achieve better anesthesia effect and rapid onset of anesthesia and has less impact on the patient’s blood pressure and heart rate, but it also can relieve pain and has good safety after the use of medication. It is worthy of clinical application.

Study of Correlation of TMT Results with Angiogram Findings in Coronary Artery Disease Predictability in Patients with Angina Equivalents in DAE Hospital

Introduction Coronary artery disease is leading cause of mortality and morbidity worldwide. The early detection and treatment of CAD is vital to prevent complications with non invasive tests like stress tests Exercise treadmill testing (ETT) is a wellvalidated, inexpensive test that can be used for the evaluation of patients with suspected coronary artery diseases (CAD). In addition to identifying patients who have exercise-induced ECG changes suggestive of ischemia, ETT also provides important data on exercise capacity, blood pressure, and heart rate response to exercise, symptoms, and the presence of exercise-induced arrhythmias. In a person at high risk for coronary heart disease (e.g., advanced age, multiple coronary risk factors), an abnormal TMT is very predictive of the presence of coronary heart disease (> 90% accurate). In the present study ,we studied the patients with changing risk factor profiles along with increasing incidence of CAD in younger population (even as young as 30-35 years), in females versus males by TMT and also the correlation of TMT results with angiogram findings in the predictability of CAD

The effect of chronotropic incompetence on physiologic responses during progressive exercise in people with Parkinson’s disease

PurposeHeart rate (HR) response is likely to vary in people with Parkinson’s disease (PD), particularly for those with chronotropic incompetence (CI). This study explores the impact of CI on HR and metabolic responses during cardiopulmonary exercise test (CPET) in people with PD, and its implications for exercise intensity prescription.MethodsTwenty-eight participants with mild PD and seventeen healthy controls underwent CPET to identify the presence or absence of CI. HR and metabolic responses were measured at submaximal (first (VT1) and second (VT2) ventilatory thresholds), and at peak exercise. Main outcome measures were HR, oxygen consumption (VO2), and changes in HR responses (HR/WR slope) to an increase in exercise demand.ResultsCI was present in 13 (46%) PD participants (PDCI), who during CPET, exhibited blunted HR responses compared to controls and PD non-CI beyond 60% of maximal workload (p ≤ 0.05). PDCI presented a significantly lower HR at VT2, and peak exercise compared to PD non-CI and controls (p ≤ 0.001). VO2 was significantly lower in PDCI than PD non-CI and controls at VT2 (p = 0.003 and p = 0.036, respectively) and at peak exercise (p = 0.001 and p = 0.023, respectively).ConclusionAlthough poorly understood, the presence of CI in PD and its effect on HR and metabolic responses during incremental exercise is significant and important to consider when programming aerobic exercises.

Hemodynamic gain index and risk of ventricular arrhythmias: a prospective cohort study.

Objectives: Hemodynamic gain index (HGI), a novel hemodynamic index obtained from cardiopulmonary exercise testing (CPX), is associated with adverse cardiovascular outcomes. However, its specific relationship with ventricular arrhythmias (VAs) is unknown. We aimed to assess the association of HGI with risk of VAs in a prospective study. Design: Hemodynamic gain index was estimated using heart rate and systolic blood pressure (SBP) responses ascertained in 1945 men aged 42-61 years during CPX from rest to maximum exercise, using the formula: [(Heart ratemax x SBPmax) - (Heart raterest x SBPrest)]/(Heart raterest x SBPrest). Cardiorespiratory fitness (CRF) was measured using respiratory gas exchange analysis. Hazard ratios (HRs) (95% confidence intervals, CIs) were estimated for VAs. Results: Over a median follow-up duration of 28.2 years, 75 cases of VA were recorded. In analysis adjusted for established risk factors, a unit (bpm/mmHg) higher HGI was associated with a decreased risk of VA (HR 0.72, 95% CI: 0.55-0.95). The results remained consistent on adjustment for lifestyle factors and comorbidities (HR 0.72, 95% CI: 0.55-0.93). Comparing the top versus bottom tertiles of HGI, the corresponding adjusted HRs (95% CIs) were 0.51 (0.27-0.96) and 0.52 (0.28-0.94), respectively. The associations were attenuated on addition of CRF to the model. HGI improved risk discrimination beyond established risk factors but not CRF. Conclusions: Higher HGI is associated with a reduced risk of VAs in middle-aged and older Caucasian men, but dependent on CRF levels. Furthermore, HGI improves the prediction of the long-term risk for VAs beyond established risk factors but not CRF.

Baroreflex dynamics during the rest to exercise transient in acute normobaric hypoxia in humans

PurposeWe hypothesised that during a rest-to-exercise transient in hypoxia (H), compared to normoxia (N), (i) the initial baroreflex sensitivity (BRS) decrease would be slower and (ii) the fast heart rate (HR) and cardiac output (CO) response would have smaller amplitude (A1) due to lower vagal activity in H than N.MethodsTen participants performed three rest-to-50 W exercise transients on a cycle-ergometer in N (ambient air) and three in H (inspired fraction of O2 = 0.11). R-to-R interval (RRi, by electrocardiography) and blood pressure profile (by photo-plethysmography) were recorded non-invasively. Analysis of the latter provided mean arterial pressure (MAP) and stroke volume (SV). CO = HR·SV. BRS was calculated by modified sequence method.ResultsUpon exercise onset in N, MAP fell to a minimum (MAPmin) then recovered. BRS decreased immediately from 14.7 ± 3.6 at rest to 7.0 ± 3.0 ms mmHg−1 at 50 W (p < 0.01). The first BRS sequence detected at 50 W was 8.9 ± 4.8 ms mmHg−1 (p < 0.05 vs. rest). In H, MAP showed several oscillations until reaching a new steady state. BRS decreased rapidly from 10.6 ± 2.8 at rest to 2.9 ± 1.5 ms mmHg−1 at 50 W (p < 0.01), as the first BRS sequence at 50 W was 5.8 ± 2.6 ms mmHg−1 (p < 0.01 vs. rest). CO-A1 was 2.96 ± 1.51 and 2.31 ± 0.94 l min−1 in N and H, respectively (p = 0.06). HR-A1 was 7.7 ± 4.6 and 7.1 ± 5.9 min−1 in N and H, respectively (p = 0.81).ConclusionThe immediate BRS decrease in H, coupled with similar rapid HR and CO responses, is compatible with a withdrawal of residual vagal activity in H associated with increased sympathetic drive.

Cannabidiol potentiates hyperpolarization-activated cyclic nucleotide-gated (HCN4) channels.

Cannabidiol (CBD), the main non-psychotropic phytocannabinoid produced by the Cannabis sativa plant, blocks a variety of cardiac ion channels. We aimed to identify whether CBD regulated the cardiac pacemaker channel or the hyperpolarization-activated cyclic nucleotide-gated channel (HCN4). HCN4 channels are important for the generation of the action potential in the sinoatrial node of the heart and increased heart rate in response to β-adrenergic stimulation. HCN4 channels were expressed in HEK 293T cells, and the effect of CBD application was examined using a whole-cell patch clamp. We found that CBD depolarized the V1/2 of activation in holo-HCN4 channels, with an EC50 of 1.6 µM, without changing the current density. CBD also sped activation kinetics by approximately threefold. CBD potentiation of HCN4 channels occurred via binding to the closed state of the channel. We found that CBD's mechanism of action was distinct from cAMP, as CBD also potentiated apo-HCN4 channels. The addition of an exogenous PIP2 analog did not alter the ability of CBD to potentiate HCN4 channels, suggesting that CBD also acts using a unique mechanism from the known HCN4 potentiator PIP2. Lastly, to gain insight into CBD's mechanism of action, computational modeling and targeted mutagenesis were used to predict that CBD binds to a lipid-binding pocket at the C-terminus of the voltage sensor. CBD represents the first FDA-approved drug to potentiate HCN4 channels, and our findings suggest a novel starting point for drug development targeting HCN4 channels.

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis.

Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b+ LY6Chigh). Furthermore, both CD11b+ Ly6Clow F4/80high macrophages (MΦ) and recently differentiated CD11b+ Ly6Chigh F4/80high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206high) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.

0090 Impact of Evening Binge Alcohol Consumption on Nocturnal Heart Rate Response to Cortical Arousal

0090 Impact of Evening Binge Alcohol Consumption on Nocturnal Heart Rate Response to Cortical Arousal

In-Season Training Load Variation - Heart Rate Recovery, Perceived Recovery Status, and Performance in Elite Male Water Polo Players: A Pilot Study.

Increased training and competition demands of the in-season period may disturb athlete fatigue and recovery balance. The aim of this study was to describe the training load distribution applied in a competitive period and the training adaptations and fatigue/recovery status of elite water polo players. Effective workload management during tapering (TAP) would restore player recovery and enhance performance. Case series. Level 4. Training load, perceived recovery, maximal speed in 100- and 200-meter swim, heart rate (HR) during submaximal swimming (HRsubmax) and HR recovery (HRR) were assessed in 7 outfield water polo players a week before starting a normal training microcycle (NM), after NM, and after congested (CON) and TAP training blocks in the lead-up to the Final Eight of the European Champions League. Training load was higher in NM compared with CON and TAP by 28.9 ± 2.6% and 42.8 ± 2.1% (P < 0.01, d = 11.54, and d = 13.45, respectively) and higher in CON than TAP by 19.4 ± 4.2% (P < 0.01, d = 3.78). Perceived recovery was lower in CON compared with NM and TAP (P < 0.01, d = 1.26 and d = 3.11, respectively) but not different between NM and TAP (P = 0.13, d = 0.62). Both 100- and 200-meter swim performance was improved in TAP compared with baseline (P < 0.01, d = 1.34 and d = 1.12, respectively). No differences were detected among other training blocks. HRsubmax and most HRR were similar among the training periods. Effective management of training load at TAP can restore recovery and improve swimming performance without affecting HR responses. Despite lower workloads, CON training impairs perceived recovery without affecting performance; however, a short-term training load reduction after a CON fixture restores recovery and improves performance.

The time course of hypoxia effects using an aviation survival trainer

IntroductionReduced environmental oxygen levels at high altitudes can result in hypoxic hypoxia, which remains a primary threat in tactical aviation. Hypoxia broadly impairs cognition and can degrade a pilot's ability to safely operate the aircraft. Current hypoxia countermeasures include aircraft life support systems that deliver supplemental oxygen and using controlled hypoxia exposures to train aviators to recognize symptoms. To maximize the effectiveness of these countermeasures, it is critical to understand how hypoxia impacts performance and associated neurocognitive outcomes. We previously showed that a neural marker that indexes sensory processing integrity is sensitive to hypoxia impairment.MethodsHere, we extend this line of research closer to the training environment by using hypoxia simulation equipment currently standard in aviation survival training. In a single-blind, repeated-measures, counterbalanced design, we exposed 34 healthy participants to either normoxic air (ground level) or normobaric hypoxia (altitude equivalent gradually increasing from 10 to 25k') for 20 min after a 10 min baseline at ground level. During the exposure, participants completed a cognitive assessment battery while passively elicited neural responses to auditory tones were recorded using electroencephalography (EEG). Participants reported their hypoxia symptoms throughout and upon completion of their exposures.ResultsWe found that the hypoxia exposure rapidly elicited the predicted physiological responses in peripheral oxygen saturation (decrease) and heart rate (increase) within 2–3 minutes of exposure onset. On average, participants reported hypoxia symptoms in a delayed manner, ~8 min following the exposure onset. Performance on the cognitive tasks was relatively unaffected by hypoxia for basic tasks including Stroop, fine motor tracking, color vision and arithmetic, but was significantly degraded by hypoxia for more advanced tasks that combined a visual search component with Stroop and a working memory task. EEG activity associated with pre-attentive auditory processing was impaired on average shortly after the first symptom report, ~10 min from exposure start.DiscussionTogether, these results move hypoxia research closer to conditions encountered in aviation survival training and support the use of training devices for future hypoxia research.

Self-paced heart rate control during treadmill exercise for persons with gait impairment: a case study

Introduction:A self-paced (SP) heart rate (HR) control system proposed in a previous study was found to be feasible for healthy participants. The aims of this work were to investigate whether the SP HR control system is feasible to achieve accurate HR control in a participant with gait impairments, and to assess its interaction with an existing motor-driven body weight support (BWS) system.Methods:One participant with cerebral palsy was recruited in this case study. Three preliminary tests were completed to determine the appropriate mean value and amplitude of the target heart rate curve, and to identify a customised heart rate response model. Two series of formal self-paced heart rate control tests were then conducted to investigate the influence of different heart rate compensators and the presence of the BWS system.Results:The customised heart rate controller achieved improved accuracy in heart rate control and reduced oscillation in the treadmill target speed: the root-mean-square heart rate tracking error (RMSE) was 2.38 beats per minute (bpm) vs. 3.91 bpm (customised controller vs. nominal controller), and the average power of changes in the treadmill target speed was 0.4 × 10−4 m2/s2 vs. 8.4 × 10−4 m2/s2. The BWS system resulted in improved HR tracking accuracy: RMSE on heart rate tracking was 3.02 bpm vs. 3.50 bpm (with BWS vs. without BWS). The BWS system had no influence on the automatic position control accuracy: RMSE on distance tracking was 0.0159 m vs. 0.0164 m.Conclusion:After customising the heart rate compensator, the self-paced heart rate control system is feasible to achieve accurate heart rate control in an individual with gait impairments, and it can correctly interact with the BWS system.

Distribution of Cardiovascular Dysautonomia Pattern across Different Stages of Chronic Kidney Disease

Context: Autonomic dysfunction (AD) brings up cardiovascular morbidity/mortality and has been reported in chronic kidney disease (CKD). Still, the pattern of AD in CKD is elusive. Aim: To evaluate the distribution of cardiovascular dysautonomia in CKD. Material and Methods: This study was conducted on 33 CKD cases and 30 age and sex matched healthy controls. Five standard autonomic function tests were conducted, namely, heart rate response to Valsalva maneuver, deep breathing, and standing, and BP response to standing and sustained handgrip; based on which the patients were classified as normal, or having early parasympathetic, definite parasympathetic and combined damage. The total autonomic function score was also calculated. Results: All cases belonged to CKD stages of 3, 4, and 5; and came up with autonomic failure. The mean total autonomic function score was higher (P &lt; 0.001) in CKD (5.09 ± 2.33) as compared to the control group (0.97 ± 0.24), using the unpaired “t” test. Most of the CKD patients (45.45%) were involved with combined damage. Of the three stages, combined damage struck stage 5 to the maximum extent (63.63%). Sympathetic failure always co occurred with parasympathetic failure. Conclusion: Combined autonomic failure is more conspicuous in late CKD, predominantly occurring in stage 5. The disease course may contort the parasympathetic system before the sympathetic system.

Cyclooxygenase products contribute to the exaggerated exercise pressor reflex evoked by static muscle contraction in male UCD-type 2 diabetes mellitus rats.

Cyclooxygenase (COX) products of arachidonic acid metabolism, specifically prostaglandins, play a role in evoking and transmitting the exercise pressor reflex in health and disease. Individuals with type 2 diabetes mellitus (T2DM) have an exaggerated exercise pressor reflex; however, the mechanisms for this exaggerated reflex are not fully understood. We aimed to determine the role played by COX products in the exaggerated exercise pressor reflex in T2DM rats. The exercise pressor reflex was evoked by static muscle contraction in unanesthetized, decerebrate, male, adult University of California Davis (UCD)-T2DM (n = 8) and healthy Sprague-Dawley (n = 8) rats. Changes (Δ) in peak mean arterial pressure (MAP) and heart rate (HR) during muscle contraction were compared before and after intra-arterial injection of indomethacin (1 mg/kg) into the contracting hindlimb. Data are presented as means ± SD. Inhibition of COX activity attenuated the exaggerated peak MAP (Before: Δ32 ± 13 mmHg and After: Δ18 ± 8 mmHg; P = 0.004) and blood pressor index (BPi) (Before: Δ683 ± 324 mmHg·s and After: Δ361 ± 222 mmHg·s; P = 0.006), but not HR (Before: Δ23 ± 8 beats/min and After Δ19 ± 10 beats/min; P = 0.452) responses to muscle contraction in T2DM rats. In healthy rats, COX activity inhibition did not affect MAP, HR, or BPi responses to muscle contraction. Inhibition of COX activity significantly reduced local production of prostaglandin E2 in T2DM and healthy rats. We conclude that peripheral inhibition of COX activity attenuates the pressor response to muscle contraction in T2DM rats, suggesting that COX products partially contribute to the exaggerated exercise pressor reflex in those with T2DM.NEW & NOTEWORTHY We compared the pressor and cardioaccelerator responses to static muscle contraction before and after inhibition of cyclooxygenase (COX) activity within the contracting hindlimb in decerebrate, unanesthetized type 2 diabetic mellitus (T2DM) and healthy rats. The pressor responses to muscle contraction were attenuated after peripheral inhibition of COX activity in T2DM but not in healthy rats. We concluded that COX products partially contribute to the exaggerated pressor reflex in those with T2DM.

Circulating catecholamines, endothelin-1, and nitric oxide releases do not explain the preserved FMD following acute resistance exercise in strength-trained men.

Acute resistance exercise decreases endothelial function in sedentary individuals but not in strength-trained (ST) individuals. However, the underlying mechanism(s) of vascular protection in ST individuals remains unclear. Herein, we compared catecholamines, endothelin-1 (ET-1), and nitric oxide (NOx) releases after acute resistance exercise between sedentary and ST individuals. The untrained (UT) group comprised 12 male individuals with no regular training, while the ST group comprised 12 male individuals. Participants performed a session of resistance exercise, which consisted of 3 sets of 10 repetitions at 75% of one repetition maximum. Heart rate (HR) and blood pressure were measured during resistance exercise. Brachial artery flow-mediated dilation (FMD), blood pressure, HR, and blood collection were undertaken before and 10, 30, and 60 min after the resistance exercise. No significant difference was found in baseline brachial artery FMD between the groups (P > 0.05). Brachial artery FMD was significantly reduced in the UT group (P < 0.05) but it was prevented in the ST group after the resistance exercise. Significant differences were found at 10, 30, and 60 min after the resistance exercise in brachial artery ΔFMD from baseline between groups (P < 0.05). Blood pressure, HR, plasma epinephrine, norepinephrine, dopamine, serum endothelin-1, and plasma NOx responses did not differ between groups throughout the experimental period. In conclusion, preserved endothelial function in response to acute resistance exercise in ST male individuals is independent of catecholamines, ET-1, and NOx responses.

Changes in cardiovascular autonomic control induced by chronic inhibition of acetylcholinesterase during pyridostigmine or donepezil treatment of spontaneously hypertensive rats

Chronic treatment with acetylcholinesterase inhibitors may be a promising therapeutic strategy for treatment of cardiovascular diseases. The aim of our study was to analyze the changes in blood pressure (BP) and heart rate (HR) during 14 days of treatment with two different acetylcholinesterase inhibitors – pyridostigmine (PYR) having only peripheral effects or donepezil (DON) with both peripheral and central effects. In addition, we studied their effects on the cardiovascular response to restraint stress and on sympathovagal control of HR in normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). SHR were characterized by elevated BP and increased low-frequency component of systolic BP variability (LF-SBPV), but their cardiac vagal tone and HR variability (HRV) were reduced compared with WKY. Chronic treatment with either acetylcholinesterase inhibitor decreased HR and increased HRV in both strains. PYR treatment slightly decreased BP and LF-SBPV in the dark phase of the day. Neither drug significantly altered BP response to stress, but PYR attenuated HR increase during restraint stress. Regarding sympathovagal balance, acute methylatropine administration caused a greater increase of HR in WKY than in SHR. Chronic PYR or DON treatment enhanced HRV and HR response to methylatropine (vagal tone) in WKY, whereas PYR but not DON treatment potentiated HRV and vagal tone in SHR. In conclusion, vagal tone was lower in SHR compared with WKY, but was enhanced by chronic PYR treatment in both strains. Thus, chronic peripheral, but not central, acetylcholinesterase inhibition has major effects on HR and its variability in both normotensive and hypertensive rats.

Effects of bi-hemispheric anodal transcranial direct current stimulation on soccer player performance: a triple-blinded, controlled, and randomized study.

The search for increased performance and physical performance are linked to the use of ergogenic resources. The vertical jump is one of the measures commonly used to evaluate the performance of lower limbs in athletes. Transcranial direct current stimulation (tDCS) is a non-invasive, safe, economically viable technique that can modulate cortical excitability, which can influence the increase in the performance of athletes in general. This study aimed to investigate whether the use of tDCS on the primary motor cortex (M1) improves the performance of soccer players. A cross-sectional study was conducted. Twenty-seven players were randomized into three groups: Active tDCS group (n = 9), Sham group (n = 9), and control group (n = 9). Stimulation was applied at 2 mA for 15 min using a cephalic mount. Visual Pain Scale (VAS) and Subjective Recovery Scale (SRS) were monitored before and after tDCS. In addition, the participants performed the Countermovement Jump (CMJ) before and after the stimulation intercalated with Heart Rate (HR) and Rating of Perceived Exertion (RPE CR-10). No differences were found in any of the performance variables analyzed (p > 0.05) nor in the responses of HR (p > 0.05), RPE (p > 0.05), VAS (p > 0.05), and SRS (p > 0.05) between groups. The tDCS in M1 did not change the performance of the vertical jump, and there was no improvement in the subjective scales. New studies should also be developed with different stimulus intensities in different cortical areas and sports modalities.

Recovery in elite youth basketball players: The responsiveness of the psychophysiological measurements and the role of testosterone concentration

ABSTRACT This study investigated the recovery responses to the Total Quality Recovery (TQR), Well-Being questionnaire (WBQ), and Heart Rate (HR) responses to Submaximal Running Test (SRT), and the influence of salivary testosterone concentration (TEST) on these responses in 25 elite youth (U15) male basketball players. TQR, WBQ, and HR measurements were assessed after 48 hours of rest (T1), 24 hours after the 1st day of training (T2) and 24 hours after the 2nd day of training (T3). Salivary sampling was conducted at T1 and T3. A significant decrease was observed for TQR (F = 4.06; p = 0.01) and for WBQ (F = 5.37; p = 0.008) from T1 to T3. No difference among the three-time points was observed for HR and HR Recovery, and the TEST concentration did not influence the results. These results show that TQR and WBQ are sensitive to acute transient alterations in training loads (TL) and may be utilized to monitor recovery in elite youth basketball players. The HR related measurements presented limited responsiveness, and the TEST seems not to influence the recovery of these players who are competing at highest performance level.

Abstract 7515: Enhancing immune checkpoint inhibitor efficacy with fulvestrant in estrogen receptor-positive breast cancer

Abstract Introduction: Breast cancer (BC) recurs decades after initial treatment that consists majority of the annual 43,000 BC deaths. Thus, Immune Checkpoint Inhibitor (ICI) therapy that bolster anti-cancer immunity is expected to improve long-term survival with reduced recurrence. Neoadjuvant ICI revolutionized management of triple negative breast cancer (TNBC); however, this represents only 5-7% of all BC cases, where estrogen receptor (ER)-positive subtype that consists of 70% of all BCs is not indicated due to less tumor-infiltrating lymphocytes (TILs). Using I-SPY2 trial we aim to investigate the potency of ER-alpha gene (ESR1) expression as a predictive biomarker, and whether the inhibition of the ER with fulvestrant enhances the efficacy of ICIs in ER+ BC. Methods:Total of 1157 BC patients from two independent cohorts (ISPY2 trial; n= 73, TCGA; n = 1084) were included, encompassing both clinical and transcriptomic profiles. The TIL score was determined using the xCell algorithm. Results:Using the transcriptome of the ISPY2 trial, we found that compared to ESR1 low expression patients, ESR1 high patients were associated with significantly lower pCR rates after neoadjuvant immunotherapy with ICI in whole cohort (n=71, pCR rate=30%, p&amp;lt;0.05) and HR+ subtype (n=50, pCR rate=20%, p&amp;lt;0.001), but not in triple-negative breast cancer (TNBC). ESR1 expression outperformed PD-1, PD-L1, and CTLA4 in Area Under the Curve (AUC) of the whole ISPY2 cohort (AUC=0.75, 0.68, 0.48, and 0.62, respectively), and further pronounced in HR+ BC (AUC=0.88, 0.73, 0.55, and 0.65, respectively), suggesting the potency of ESR1 expression as a predictive biomarker for ICI in HR+ BC. In agreement, ESR1 expression inversely correlated with the amount of intratumoral TILs consistently in both ISPY2 and TCGA cohorts in HR+ BC, but only in TCGA in whole cohort (all p&amp;lt;0.05). Among the intratumoral TILs, CD8+ T cell and M1 Macrophages were found to be less infiltrated in HR+ BC in TCGA. Given that ESR1 expression was associated with less intratumoral TILs and a poor response to ICI, we hypothesized that suppression of ER-alpha would enhance the effectiveness of ICI in HR+ BC in vitro. ER-alpha positive MCF7 cells were incubated with activated peripheral blood mononuclear cells with 1:1 ratio, and treated with 0.1 microgram of anti-PDL1, and 1nM of ER antagonist, fulvestrant, which demonstrated minimum cell killing. We found that ICI therapy with anti-PDL1 significantly decreased the cell viability of the MCF7 cells when ER-alpha expression was suppressed by fulvestrant, while activated peripheral blood mononuclear cells or anti-PDL1 alone or the combination did not exhibit any significant cell killing. Conclusion: We found that ESR1 expression is a predictive biomarker of ICI, and ER antagonist fulvestrant enhances the response of HR+ BC to ICI, suggesting that this combination could expand ICI indications to HR+ BC. Citation Format: Jun Arima, Kohei Chida, Masanori Oshi, Arya Mariam Roy, Kohei Taniguchi, Sang-Woong Lee, Kazuaki Takabe. Enhancing immune checkpoint inhibitor efficacy with fulvestrant in estrogen receptor-positive breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7515.