Abnormal Cardiovascular Responses Research Articles

Absent Right Coronary Artery in an Active Young Female

Absent Right Coronary Artery in an Active Young Female

The role of post-translational modifications in driving abnormal cardiovascular complications at high altitude.

The high-altitude environment is characterized by hypobaric hypoxia, low temperatures, low humidity, and high radiation, which is a natural challenge for lowland residents entering. Previous studies have confirmed the acute and chronic effects of high altitude on the cardiovascular systems of lowlanders. Abnormal cardiovascular complications, including pulmonary edema, cardiac hypertrophy and pulmonary arterial hypertension were commonly explored. Effective evaluation of cardiovascular adaptive response in high altitude can provide a basis for early warning, prevention, diagnosis, and treatment of altitude diseases. At present, post-translational modifications (PTMs) of proteins are a key step to regulate their biological functions and dynamic interactions with other molecules. This process is regulated by countless enzymes called “writer, reader, and eraser,” and the performance is precisely controlled. Mutations and abnormal expression of these enzymes or their substrates have been implicated in the pathogenesis of cardiovascular diseases associated with high altitude. Although PTMs play an important regulatory role in key processes such as oxidative stress, apoptosis, proliferation, and hypoxia response, little attention has been paid to abnormal cardiovascular response at high altitude. Here, we reviewed the roles of PTMs in driving abnormal cardiovascular complications at high altitude.

Correction of the Elevated Blood Pressure in Patients Undergoing Robot-Assisted Radical Prostatectomy

The aim of the study was to evaluate the role of urapidil hydrochloride for the management of abnormal cardiovascular response in patients undergoing robot-assisted radical prostatectomy (RARP).Material and methods. The total of 93 prostate cancer patients scheduled for elective RARP were included and randomized in two groups: urapidil (n=44) and standard anesthesia control group (n=49). Urapidil was used to control the elevated blood pressure intraoperatively. Central hemodynamic monitoring was performed at 5 steps of the surgery.Results. In the control group, the step 2 of the procedure was associated with elevated mean blood pressure (by 24.3%, P=0.045) and increased total peripheral vascular resistance (by 46.6%, P=0.011) compared with step 1, while in the urapidil group no significant changes in these parameters were found. In the urapidil group, the blood pressure was lower by 20.2% (P=0.047), afterload by 36.9% (P=0.02) vs the control group values, whereas the cardiac output was higher by 22.2% (P=0.043). Placing patient in the steep Trendelenburg position (step 3) resulted in a 22.4% increase in stroke volume (P=0.38) in the control group and a 19.2% increase in stroke volume (P=0.049) in the urapidil group compared with the previous step. Cardiac output in the urapidil group was higher by 34% (P=0.002) and blood pressure and vascular resistance were lower by 24.4% (P=0.031) and 45.7% (P=0.001), respectively, vs the control group. At steps 4 and 5, gradual stabilization of the hemodynamic parameters and peripheral vascular tone with significantly smaller differences between the groups were revealed.Conclusion. Urapidil was effective for maintaining central hemodynamic parameters in patients during robotic-assisted radical prostatectomy at step 2 of the procedure, avoiding blood pressure elevation at step 3 and significantly reducing the total peripheral vascular resistance compared with the control group.

The exercise pressor reflex: An update.

The exercise pressor reflex is a feedback mechanism engaged upon stimulation of mechano- and metabosensitive skeletal muscle afferents. Activation of these afferents elicits a reflex increase in heart rate, blood pressure, and ventilation in an intensity-dependent manner. Consequently, the exercise pressor reflex has been postulated to be one of the principal mediators of the cardiorespiratory responses to exercise. In this updated review, we will discuss classical and recent advancements in our understating of the exercise pressor reflex function in both human and animal models. Particular attention will be paid to the afferent mechanisms and pathways involved during its activation, its effects on different target organs, its potential role in the abnormal cardiovascular response to exercise in diseased states, and the impact of age and biological sex on these responses. Finally, we will highlight some unanswered questions in the literature that may inspire future investigations in the field.

Blood pressure and heart rate responses to orthostatic challenge and Valsalva manoeuvre in mild cognitive impairment with Lewy bodies.

ObjectivesOrthostatic hypotension is a common feature of normal ageing, and age‐related neurodegenerative diseases, in particular the synucleinopathies including dementia with Lewy bodies. Orthostatic hypotension and other abnormal cardiovascular responses may be early markers of Lewy body disease. We aimed to assess whether abnormal blood pressure and heart rate responses to orthostatic challenge and Valsalva manoeuvre would be more common in mild cognitive impairment with Lewy bodies (MCI‐LB) than MCI due to Alzheimer's disease (MCI‐AD).MethodsMCI patients (n = 89) underwent longitudinal clinical assessment with differential classification of probable MCI‐LB, possible MCI‐LB, or MCI‐AD, with objective autonomic function testing at baseline. Blood pressure and heart rate responses to active stand and Valsalva manoeuvre were calculated from beat‐to‐beat cardiovascular data, with abnormalities defined by current criteria, and age‐adjusted group differences estimated with logistic models.ResultsOrthostatic hypotension and abnormal heart rate response to orthostatic challenge were not more common in probable MCI‐LB than MCI‐AD. Heart rate abnormalities were likewise not more common in response to Valsalva manoeuvre in probable MCI‐LB. An abnormal blood pressure response to Valsalva (delayed return to baseline/absence of overshoot after release of strain) was more common in probable MCI‐LB than MCI‐AD. In secondary analyses, magnitude of blood pressure drop after active stand and 10‐s after release of Valsalva strain were weakly correlated with cardiac sympathetic denervation.ConclusionsProbable MCI‐LB may feature abnormal blood pressure response to Valsalva, but orthostatic hypotension is not a clear distinguishing feature from MCI‐AD.

A Useful Blood Flow Restriction Training Risk Stratification for Exercise and Rehabilitation.

Blood flow restriction training (BFRT) is a modality with growing interest in the last decade and has been recognized as a critical tool in rehabilitation medicine, athletic and clinical populations. Besides its potential for positive benefits, BFRT has the capability to induce adverse responses. BFRT may evoke increased blood pressure, abnormal cardiovascular responses and impact vascular health. Furthermore, some important concerns with the use of BFRT exists for individuals with established cardiovascular disease (e.g., hypertension, diabetes mellitus, and chronic kidney disease patients). In addition, considering the potential risks of thrombosis promoted by BFRT in medically compromised populations, BFRT use warrants caution for patients that already display impaired blood coagulability, loss of antithrombotic mechanisms in the vessel wall, and stasis caused by immobility (e.g., COVID-19 patients, diabetes mellitus, hypertension, chronic kidney disease, cardiovascular disease, orthopedic post-surgery, anabolic steroid and ergogenic substance users, rheumatoid arthritis, and pregnant/postpartum women). To avoid untoward outcomes and ensure that BFRT is properly used, efficacy endpoints such as a questionnaire for risk stratification involving a review of the patient’s medical history, signs, and symptoms indicative of underlying pathology is strongly advised. Here we present a model for BFRT pre-participation screening to theoretically reduce risk by excluding people with comorbidities or medically complex histories that could unnecessarily heighten intra- and/or post-exercise occurrence of adverse events. We propose this risk stratification tool as a framework to allow clinicians to use their knowledge, skills and expertise to assess and manage any risks related to the delivery of an appropriate BFRT exercise program. The questionnaires for risk stratification are adapted to guide clinicians for the referral, assessment, and suggestion of other modalities/approaches if/when necessary. Finally, the risk stratification might serve as a guideline for clinical protocols and future randomized controlled trial studies.

Cardiopulmonary exercise test in patients with refractory angina: functional and ischemic evaluation

ObjectivesRefractory angina (RA) is a chronic condition clinically characterized by low effort tolerance; therefore, physical stress testing is not usually requested for these patients. Cardiopulmonary exercise testing (CPET) is considered a gold standard examination for functional capacity evaluation, even in submaximal tests, and it has gained great prominence in detecting ischemia. The authors aimed to determine cardiorespiratory capacity by using the oxygen consumption efficiency slope (OUES) in patients with refractory angina. The authors also studied the O2 pulse response by CPET and the association of ischemic changes with contractile modifications by exercise stress echocardiography (ESE). MethodsThirty-one patients of both sexes, aged 45 to 75 years, with symptomatic (Canadian Cardiovascular Society class II to IV) angina who underwent CPET on a treadmill and exercise stress echocardiography on a lower limb cycle ergometer were studied. ClinicalTrials.gov: NCT03218891. ResultsThe patients had low cardiorespiratory capacity (OUES of 1.74 ± 0.4 L/min; 63.9±14.7% of predicted), and 77% of patients had a flattening or drop in O2 pulse response. There was a direct association between Heart Rate (HR) at the onset of myocardial ischemia detected by ESE and HR at the onset of flattening or drop in oxygen pulse response detected by CPET (R = 0.48; p = 0.019). ConclusionPatients with refractory angina demonstrate low cardiorespiratory capacity. CPET shows good sensitivity for detecting abnormal cardiovascular response in these patients with a significant relationship between flattening O2 pulse response during CEPT and contractile alterations detected by exercise stress echocardiography.

OSA and cardiorespiratory fitness: a review.

Powell TA, Mysliwiec V, Brock MS, Morris MJ. OSA and cardiorespiratory fitness: a review. J Clin Sleep Med. 2022;18(1):279-288.

Analysis of cardiovascular responses to head-up tilt testing

Introduction: Head-up tilt (HUT) testing is a widely accepted tool in the clinical evaluation of patients presenting with episodic loss of consciousness. The test has assumed its importance in aviation environment, where a single episode of unconsciousness in-flight may have a catastrophic outcome. To rule out this, HUT is carried out in all cases of syncope as a part of aeromedical evaluation. The present study was undertaken to analyze the CVS response to HUT conducted over a period of 11 years at the Department of Space and Environmental Physiology at the Institute of Aerospace Medicine. Material and Methods: A total of 168 subjects had undergone HUT testing from 2002 to 2012. The testing equipment was a standard tilt table with a foot board support for the feet and restraint system at the level of chest, waist, and ankle to support the body during tilting. The testing protocol consisted of passive tilting to an angle of 70° from the horizontal position for 45 min in all the cases. The physiological parameters consisting of heart rate (HR) and blood pressure from the database were analyzed to understand the CVS response to HUT. Results: Out of the total 168 patients, 147 (88.5%) cases showed normal response. Twenty-one (12.5%) cases showed abnormal response. Out of the cases showing abnormal response, 14 cases had syncope with frank loss of consciousness and could not maintain the postural tone. The remaining seven cases showed postural orthostatic tachycardia syndrome (POTS), where the HR increased by more than 30 beats per minute. Conclusion: A retrospective analysis of 168 cases with history of syncope, in a period of 11 years, revealed an abnormal cardiovascular response to HUT in 12.5% of cases. The abnormal physiological responses were mostly consistent with syncope and POTS.

Increased sympathetic and haemodynamic responses to exercise and muscle metaboreflex activation in post-menopausal women with rheumatoid arthritis.

Rheumatoid arthritis (RA) patients present exacerbated blood pressure responses to exercise, but little is known regarding the underlying mechanisms involved. This study assessed autonomic and haemodynamic responses to exercise and to the isolated activation of muscle metaboreflex in post-menopausal women with RA. Participants with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These responses were associated with multiple pro- and anti-inflammatory cytokines and with pain. The results of the present study support the suggestion that an abnormal reflex control of circulation is an important mechanism underlying the exacerbated cardiovascular response to exercise and increased cardiovascular risk in RA. Studies have reported abnormal cardiovascular responses to exercise in rheumatoid arthritis (RA) patients, but little is known regarding the underlying mechanisms involved. This study assessed haemodynamic and sympathetic responses to exercise and to the isolated activation of muscle metaboreflex in women diagnosed with RA. Thirty-three post-menopausal women diagnosed with RA and 10 matched controls (CON) participated in this study. Mean arterial pressure (MAP), heart rate (HR) and muscle sympathetic nerve activity (MSNA frequency and incidence) were measured during a protocol of isometric knee extension exercise (3min, 30% of maximal voluntary contraction), followed by post-exercise ischaemia (PEI). Participants with RA showed greater increases in MAP and MSNA during exercise and PEI than CON (ΔMAPexercise =16±11 vs. 9±6mmHg, P=0.03; ΔMAPPEI =15±10 vs. 5±5mmHg, P=0.001; ΔMSNAexercise =17±14 vs. 7±9burstsmin-1 , P=0.04; ΔMSNAPEI =14±10 vs. 6±4burstsmin-1 , P=0.04). Autonomic responses to exercise showed significant (P<0.05) association with pro- (i.e. IFN-γ, IL-8, MCP-1 and TNFα) and anti-inflammatory (i.e. IL-1ra and IL-10) cytokines and with pain. In conclusion, post-menopausal women with RA showed augmented pressor and sympathetic responses to exercise and to the activation of muscle metaboreflex. These findings provide mechanistic insights that may explain the abnormal cardiovascular responses to exercise in RA.

Clinical Implications for Cardiovascular Compromise in Patients With Spinal Cord Injury: A Case Study of Autonomic Dysreflexia, Cardiac Pacing Abnormality, and Orthostatic Hypotension in Contemporary Physical Therapy Management

Purpose: Although recent advances in the neurological care of spinal cord injury have made great strides, cardiovascular disease has emerged as a leading contributor to mortality within this population. Achieving a greater understanding of the pathophysiology of acute cardiovascular dysfunction may aid the physical therapist in establishing more effective clinical care and decision making. The purpose of this article is to review the pathophysiology of acute cardiovascular dysfunction after cervical and thoracic spinal cord injury (injuries above the T6 vertebrae) and translate this knowledge to the clinical management of a medically complex patient case. Methods: A 62-year-old man sustained a traumatic sensory and motor complete T2 spinal cord injury. During the course of acute hospitalization, the patient suffered multiple episodes of cardiac arrest, and a permanent pacemaker was implanted. Inpatient rehabilitation was further complicated by orthostatic hypotension and emergence of autonomic dysreflexia. Results: Orthostatic hypotension was addressed with a combination of positional tolerance progression and patient education. Autonomic dysreflexia episodes required prompt recognition and appropriate response. After a 6-month hospitalization, the patient was discharged to home. Conclusion: Cardiovascular concerns after spinal cord injury have become increasingly prevalent leading to significant implications to physical therapists. Understanding the pathophysiology of these conditions as well as normal and abnormal cardiovascular responses to activity is crucial for establishing safe patient outcomes.

Protocol for a randomised controlled feasibility trial of exercise rehabilitation for people with postural tachycardia syndrome: the PULSE study

BackgroundPostural orthostatic tachycardia syndrome (POTS) is an autonomic nervous system disorder causing an abnormal cardiovascular response to upright posture. It affects around 0.2% of the population, most commonly women aged 13 to 50 years. POTS can be debilitating; prolonged episodes of pre-syncope and fatigue can severely affect activities of daily living and health-related quality of life (HRQoL). Medical treatment is limited and not supported by randomised controlled trial (RCT) evidence. Lifestyle interventions are first-line treatment, including increased fluid and salt intake, compression tights and isometric counter-pressure manoeuvres to prevent fainting. Observational studies and small RCTs suggest exercise training may improve symptoms and HRQoL in POTS, but evidence quality is low.MethodsSixty-two people (aged 18–40 years) with a confirmed diagnosis of POTS will be invited to enrol on a feasibility RCT with embedded qualitative study. The primary outcome will be feasibility; process-related measures will include the number of people eligible, recruited, randomised and withdrawn, along with indicators of exercise programme adherence and acceptability. Secondary physiological, clinical and health-related outcomes including sub-maximal recumbent bike exercise test, active stand test and HRQoL will be measured at 4 and 7 months post-randomisation by researchers blinded to treatment allocation. The PostUraL tachycardia Syndrome Exercise (PULSE) intervention consists of (1) individual assessment; (2) 12-week, once to twice-weekly, supervised out-patient exercise training; (3) behavioural and motivational support; and (4) guided lifestyle physical activity. The control intervention will be best-practice usual care with a single 30-min, one-to-one practitioner appointment, and general advice on safe and effective physical activity. For the embedded qualitative study, participants (n = 10 intervention, n = 10 control) will be interviewed at baseline and 4 months post-randomisation to assess acceptability and the feasibility of progressing to a definitive trial.DiscussionThere is very little high-quality research investigating exercise rehabilitation for people with POTS. The PULSE study will be the first randomised trial to assess the feasibility of conducting a definitive multicentre RCT testing supervised exercise rehabilitation with behavioural and motivational support, compared to best-practice usual care, for people with POTS.Trial registrationISRCTN45323485 registered on 7 April 2020.

Chronotropic Intolerance In Patients With Chronic Lyme Disease Identified By Serial Cardiopulmonary Exercise Testing

In the U.S., annual incidence of Lyme disease is approximately 300,000. In an estimated 5-30% of cases, post-treatment Lyme disease syndrome (PTLDS) develops; symptoms include post-exertional malaise characteristic of myalgic encephalomyelitis. The contribution of autonomic regulation has not been elucidated. PURPOSE: To evaluate cardiovascular responses to serial cardiopulmonary testing in patients with PTLDS. METHODS: 14 patients with PTLDS and 8 sedentary controls underwent 2 maximal exercise tests separated by 24 hours. Heart rate (HR) was measured continuously via electrocardiogram. Expired air was collected for determination of anaerobic threshold (AT) using V-slope methodology and maximal exertion was defined as a respiratory exchange ratio >1.09. Independent-samples t-tests compared baseline characteristics of PTLDS patients and controls. Linear regression determined the effect of PTLDS diagnosis on HR at AT and peak holding workload constant. RESULTS: Patients were 44.0±10.1 years old, weighed 69.8±16.2 kg, and achieved a peak VO2 of 23.8±6.2 mL/kg/min during test 1. HR was 116.2±21.8 bpm at AT and 162.6±25.1 at peak. PTLDS and controls did not differ in peak VO2 during test 1 (p=0.161), test 2 (p=0.134), or the difference between test 1 and test 2 (p=0.498). HR at AT was comparable in test 1 (p=0.127) but different in test 2 (p<0.001). HR at peak was different in test 1 (p=0.001) and test 2 (p<0.001). During test 1, holding workload constant, PTLDS patients had lower peak HR by 19.5 bpm (p=0.033; 95% CI: -37.3 to -1.8). During test 2, holding workload constant, PTLDS predicted a lower HR by 26.8 bpm at AT (p=0.004; 95% CI: -43.9 to -9.8) and 24.3 bpm at peak (p=0.007; 95% CI: -40.9±-7.7). CONCLUSIONS: Patients with PTLDS demonstrated abnormal cardiovascular responses to exercise. Despite accomplishing the same VO2, and holding workload constant, the HR response was diminished in the post-exertional state, potentially indicating dysautonomia in PTLDS.

Impact of age, sex and heart rate variability on the acute cardiovascular response to isometric handgrip exercise.

Isometric handgrip exercise (IHG) triggers acute increases in cardiac output to meet the metabolic demands of the active skeletal muscle. An abnormal cardiovascular response to IHG might reflect early stages of cardiovascular disease. In a large community-based cohort, we comprehensively assessed the clinical correlates of acute cardiovascular changes during IHG. In total, 333 randomly recruited subjects (mean age, 53 ± 13 years, 45% women) underwent simultaneous echocardiography and finger applanation tonometry at rest and during 3 min of IHG at 40% maximal handgrip force. We calculated time-domain measures of short-term heart rate variability (HRV) from finger pulse intervals. We assessed the adjusted associations of changes in blood pressure (BP) and echocardiographic indexes with clinical characteristics and HRV measures. During IHG, men presented a stronger absolute increase in heart rate, diastolic BP, left ventricular (LV) volumes and cardiac output than women, even after adjustment for covariables. In adjusted continuous and categorical analyses, age correlated positively with the increase in systolic BP and pulse pressure, but negatively with the increase in LV stroke volume and cardiac output during exercise. After full adjustment, a greater increase in systolic and diastolic BP during exercise was associated with lower absolute real variability (P ≤ 0.026) and root mean square of successive differences (P ≤ 0.032) in pulse intervals at rest. In a general population sample, women presented a weaker cardiovascular response to IHG than men. Older age was associated with greater rise in BP pulsatility and diminished cardiac reserve. Low HRV at rest predicted a higher BP increase during isometric exercise.

The role of endothelin A receptors in peripheral vascular control at rest and during exercise in patients with hypertension

Exercise in patients with hypertension can be accompanied by an abnormal cardiovascular response that includes attenuated blood flow and an augmented pressor response. Endothelin-1, a very potent vasoconstrictor, is a key modulator of blood flow and pressure during in health and has been implicated as a potential cause of the dysfunction in hypertension. We assessed the role of endothelin-1, acting through endothelin A (ETA ) receptors, in modulating the central and peripheral cardiovascular responses to exercise in patients with hypertension via local antagonism of these receptors during exercise. ETA receptor antagonism markedly increased leg blood flow, vascular conductance, oxygen delivery, and oxygen consumption during exercise; interestingly, these changes occurred in the presence of reduced leg perfusion pressure, indicating that these augmentations were driven by changes in vascular resistance. These data indicate that ETA receptor antagonism could be a viable therapeutic approach to improve blood flow during exercise in hypertension. Patients with hypertension can exhibit impaired muscle blood flow and exaggerated increases in blood pressure during exercise. While endothelin (ET)-1 plays a role in regulating blood flow and pressure during exercise in health, little is known about the role of ET-1 in the cardiovascular response to exercise in hypertension. Therefore, eight volunteers diagnosed with hypertension were studied during exercise with either saline or BQ-123 (ETA receptor antagonist) infusion following a 2-week withdrawal of anti-hypertensive medications. The common femoral artery and vein were catheterized for drug infusion, blood collection and blood pressure measurements, and leg blood flow was measured by Doppler ultrasound. Patients exercised at both absolute (0, 5, 10, 15W) and relative (40, 60, 80% peak power) intensities. BQ-123 increased blood flow at rest (79±87ml/min; P=0.03) and augmented the exercise-induced hyperaemia at most intensities (80% saline: Δ3818±1222 vs. BQ-123: Δ4812±1469ml/min; P=0.001). BQ-123 reduced leg MAP at rest (-8±4mmHg; P<0.001) and lower intensities (0-10W; P<0.05). Systemic diastolic blood pressure was reduced (0W, 40%; P<0.05), but systemic MAP was defended by an increased cardiac output. The exercise pressor response (ΔMAP) did not differ between conditions (80% saline: 25±10, BQ-123: 30±7mmHg; P=0.17). Thus, ET-1, acting through the ETA receptors, contributes to the control of blood pressure at rest and lower intensity exercise in these patients. Furthermore, the finding that ET-1 constrains the blood flow response to exercise suggests that ETA receptor antagonism could be a therapeutic approach to improve blood flow during exercise in hypertension.

Clinical safety of blood flow-restricted training? A comprehensive review of altered muscle metaboreflex in cardiovascular disease during ischemic exercise.

Blood flow restriction training (BFRT) is an increasingly widespread method of exercise that involves imposed restriction of blood flow to the exercising muscle. Blood flow restriction is achieved by inflating a pneumatic pressure cuff (or a tourniquet) positioned proximal to the exercising muscle before, and during, the bout of exercise (i.e., ischemic exercise). Low-intensity BFRT with resistance training promotes comparable increases in muscle mass and strength observed during high-intensity exercise without blood flow restriction. BFRT has expanded into the clinical research setting as a potential therapeutic approach to treat functionally impaired individuals, such as the elderly, and patients with orthopedic and cardiovascular disease/conditions. However, questions regarding the safety of BFRT must be fully examined and addressed before the implementation of this exercise methodology in the clinical setting. In this respect, there is a general concern that BFRT may generate abnormal reflex-mediated cardiovascular responses. Indeed, the muscle metaboreflex is an ischemia-induced, sympathoexcitatory pressor reflex originating in skeletal muscle, and the present review synthesizes evidence that BFRT may elicit abnormal cardiovascular responses resulting from increased metaboreflex activation. Importantly, abnormal cardiovascular responses are more clearly evidenced in populations with increased cardiovascular risk (e.g., elderly and individuals with cardiovascular disease). The evidence provided in the present review draws into question the cardiovascular safety of BFRT, which clearly needs to be further investigated in future studies. This information will be paramount for the consideration of BFRT exercise implementation in clinical populations.

Abnormal cardiovascular response to nitroglycerin in migraine.

IntroductionMigraine and vasovagal syncope are comorbid conditions that may share part of their pathophysiology through autonomic control of the systemic circulation. Nitroglycerin can trigger both syncope and migraine attacks, suggesting enhanced systemic sensitivity in migraine. We aimed to determine the cardiovascular responses to nitroglycerin in migraine.MethodsIn 16 women with migraine without aura and 10 age- and gender-matched controls without headache, intravenous nitroglycerin (0.5 µg·kg−1·min−1) was administered. Finger photoplethysmography continuously assessed cardiovascular parameters (mean arterial pressure, heart rate, cardiac output, stroke volume and total peripheral resistance) before, during and after nitroglycerin infusion.ResultsNitroglycerin provoked a migraine-like attack in 13/16 (81.2%) migraineurs but not in controls (p = .0001). No syncope was provoked. Migraineurs who later developed a migraine-like attack showed different responses in all parameters vs. controls (all p < .001): The decreases in cardiac output and stroke volume were more rapid and longer lasting, heart rate increased, mean arterial pressure and total peripheral resistance were higher and decreased steeply after an initial increase.DiscussionMigraineurs who developed a migraine-like attack in response to nitroglycerin showed stronger systemic cardiovascular responses compared to non-headache controls. The stronger systemic cardiovascular responses in migraine suggest increased systemic sensitivity to vasodilators, possibly due to insufficient autonomic compensatory mechanisms.

Sympathetic Overactivity and Increased Cardiovascular Responses to Muscle Metaboreflex Activation in Post‐menopausal Women with Rheumatoid Arthritis

AIMTo investigate the effects of rheumatoid arthritis (RA) on resting cardiovascular autonomic function and on pressor and sympathetic responses to muscle mechanoreflex and metaboreflex activation.METHODSThirty‐seven post‐menoupausal women with RA (60±7 yrs, 27.1±4.9 kg/m2, 19.2±4.7 ml.kg−1.min−1) and 9 matched controls (CON) (59±7 yrs, 26.1±3.3 kg/m2, 22.7±2.3 ml.kg−1.min−1) took part on this cross‐sectional study. Assessments included resting mean arterial pressure (MAP), heart rate (HR), muscle sympathetic nerve activity (MSNA, bursts frequency and incidence), heart rate variability (HRV), and spontaneous baroreflex sensitivity (BRS, gain and baroreflex effectiveness index [BEI]). In addition, MAP, HR, and MSNA in response to muscle mechanoreflex (passive stretching of posterior thigh) and muscle metaboreflex (post‐exercise circulatory occlusion [PECO] following static knee extension at 30% of maximal voluntary contraction) were assessed. Comparison between RA and CON was performed using a Student's t test. RA participants were grouped according to disease activity (Remission – DAS28 &lt; 2.6; Low‐to‐moderate activity – DAS28 ≥ 2.6) and duration (Group 1 &lt; 8.5 years; Group 2 = 8.5–17.5 years; Group 3 = 17.15–27.75 years; Group 4 ≥ 27.75 years), and results were compared using One‐way ANOVA. Associations between main outcomes and clinical characteristics (i.e., inflammation, disease activity, disease duration, quality of life, and pain) were performed using a Pearson product‐moment correlation coefficient. Significance level was set at p &lt; 0.05.RESULTSParticipants with RA presented greater MSNA (48±11 vs. 31±15 bursts.min−1, p&lt;0.01) and reduced BRS (BEI = 0.32±0.18 vs. 0.47±0.13, p=0.01) at rest when compared with CON. Increases in MAP, HR and MSNA during PECO were significantly greater in RA than CON (all p&lt;0.05). Additional analyses showed that MAP responses to muscle metaboreflex activation were greater in RA patients in low‐to‐moderate active disease compared with those in remission (18±11 vs. 11±8 mmHg, p=0.05), and in those with longer disease duration (Group 4: 25±7; Group 1: 10±8 mmHg; p &lt;0.01). Pressor responses to metaboreflex activation were positively correlated with C‐reactive protein levels (r=0.56, p=0.03). Responses to mechanoreflex activation were not different between groups.CONCLUSIONPatients with RA presented baroreflex impairment and sympathetic overactivity at rest and augmented cardiovascular responses to the activation of muscle metaboreflex. These abnormal neural and cardiovascular responses might contribute to the increase in cardiovascular risk in RA.Support or Funding InformationFAPESP 2016/23319‐0This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Concussed Athletes Exhibit Impaired Tolerance to a Central Hypovolemic Challenge

Concussed patients exhibit autonomic dysfunction that likely contributes to abnormal cardiovascular responses to head‐up tilt and sit‐to‐stand tests. However, these tests also activate the vestibular system, whereas lower body negative pressure (LBNP) induces central hypovolemia without vestibular activation. It is unknown if concussed patients exhibit abnormal cardiovascular responses to LBNP.PURPOSEWe tested the hypothesis that symptomatic concussed athletes (CA) have a greater reduction in blood pressure during LBNP vs. healthy controls (HC).METHODSTen CA (age: 19±2 y, 7 females) and ten HC (age: 21±2 y, 6 females) completed one study visit. After 5 min of resting baseline, 40 mmHg of LBNP was applied for up to 5 min to induce central hypovolemia. Heart rate (HR; ECG), mean arterial pressure (MAP; photoplethysmography), stroke volume (SV; Modelflow), middle cerebral artery blood velocity (MCAv; transcranial Doppler), and end tidal partial pressure of carbon dioxide (ETCO2) were recorded continuously. Cerebral vascular resistance (CVR) was calculated as MAP/MCAv. The change in HR divided by the change in MAP was calculated as an indicator of cardiac baroreflex sensitivity. CA completed a visual analogue concussion symptom scale (VAS) pre and post‐LBNP. Mean values across every min of LBNP were recorded for analyses. Outcome variables are reported and analyzed as a change from baseline for the first 60 s (stage 1) and the final stage because LBNP was terminated early due to some participants exhibiting signs of pre‐syncope (CA: n = 6; HC: n = 2).RESULTSHR (CA: 60±10 vs HC: 63±10 bpm; P=0.22), MAP (CA: 93±10 vs HC: 95±6 mmHg; P=0.31), SV (CA: 88±10 vs HC: 96±32 mL; P=0.24), MCAv (CA: 63±17 vs HC: 64±11 cm/s; P=0.41), ETCO2 (CA: 45±2 vs HC: 45±3 mmHg; P=0.37), and CVR (CA: 1.57±0.37 vs HC: 1.55±0.27 mmHg/cm/s; P=0.37) were not different at baseline. At stage 1, the change in HR (CA: 27±9 vs HC: 21±8 bpm; P=0.39), MAP (CA: −13±4 vs HC: −10±4 mmHg; P=0.57), SV (CA: −40±11 vs HC: −30±15 mL; P=0.31), MCAv (CA: −11±5 vs HC: −15±20 cm/s; P=0.69), ETCO2 (CA: −5±2 vs HC: −3±2 mmHg; P=0.16), CVR (CA: 0.09±0.11 vs HC: 0.09±0.22 mmHg/cm/s; P=0.97), and the HR/MAP ratio (CA: −2.28±1.59 vs HC: −2.52±1.77 bpm/mmHg; P=0.82) were not different between CA and HC. At the final stage, the change in HR (CA: 31±19 vs HC: 40±21 bpm; P=0.20), MAP (CA: −28±17 vs HC: −23±17 mmHg; P=0.39), SV (CA: −39±18 vs HC: −45±27 mL; P=0.54), MCAv (CA: −16±7 vs HC: −19±8 cm/s; P=0.35), and ETCO2 (CA: −6±3 vs HC: 7±5 mmHg; P=0.62) were not different between CA and HC. The change in CVR (CA: −0.09±0.28 vs HC: 0.15±0.26 mmHg/cm/s; P=0.05) and the HR/MAP ratio (CA: −0.43±4.07 vs HC: −2.90±2.38; P=0.02) were different between CA and HC at the final stage. Total LBNP time was lower in CA (201±95 s) vs HC (270±64 s; P=0.04). The VAS score increased in CA from pre‐LBNP (2±2) to post‐LBNP (4±2; P=0.02).CONCLUSIONCA had an impaired tolerance to LBNP likely due to a reduction in cardiac baroreflex sensitivity. CA also had a reduction in CVR during LBNP, which may be indicative of abnormal cerebral autoregulation during a decrease in MAP.Support or Funding InformationNIH Grant UL1TR001412This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Hemodynamic responses to an exercise stress test in Parkinson's disease patients without orthostatic hypotension.

The presence of postganglionic sympathetic denervation is well established in Parkinson's disease (PD). Denervation at cardiac and blood vessel sites may lead to abnormal cardiovascular and hemodynamic responses to exercise. The aim of the present investigation was to examine how heart rate (HR) and hemodynamics are affected by an exercise test in PD patients without orthostatic hypotension. Thirty individuals without orthostatic hypotension, 14 individuals with PD, and 16 age-matched healthy controls performed an exercise test on a cycle ergometer. Heart rate, blood pressure, and other hemodynamic variables were measured in a fasted state during supine rest, active standing, exercise, and supine recovery. Peak HR and percent of age-predicted maximum HR (HRmax) achieved were significantly blunted in PD (p < 0.05, p < 0.01). HR remained significantly elevated in PD during recovery compared with controls (p = 0.03, p < 0.05). Systolic, diastolic, and mean arterial pressures were significantly lower at multiple time-points during active standing in PD compared with controls. Systemic vascular resistance index (SVRI) decreased significantly at the onset of exercise in PD, and remained significantly lower during exercise and the first minute of supine recovery. End diastolic volume index (EDVI) was significantly lower in PD during supine rest and recovery. Our results indicate for the first time that normal hemodynamics are disrupted during orthostatic stress and exercise in PD. Despite significant differences in EDVI at rest and during recovery, and SVRI during exercise, cardiac index was unaffected. Our finding of significantly blunted HRmax and HR recovery in PD patients has substantial implications for exercise prescription and recovery guidelines.