Control Exercise Recovery Research Articles

Cardiovascular Responses to Simultaneous Diving and Muscle Metaboreflex Activation.

Background: The aim of study was to assess hemodynamic changes during the simultaneous activation of muscle metaboreflex (MM) and diving reflex (DR) in a laboratory setting. We hypothesized that as long as the exercise intensity is mild DR can overwhelm the MM.Methods: Ten trained divers underwent all four phases (randomly assigned) of the following protocol. (A) Postexercise muscle ischemia session (PEMI): 3 min of resting followed by 3 min of handgrip at 30% of maximum force, followed immediately by 3 min of PEMI on the same arm induced by inflating a sphygmomanometer. Three minutes of recovery was further allowed after the cuff was deflated for a total of 6 min of recovery. (B) Control exercise recovery session: the same rest-exercise protocol used for A followed by 6 min of recovery without inflation. (C) DR session: the same rest-exercise protocol used for A followed by 1 min of breath-hold (BH) with face immersion in cold water. (D) PEMI-DR session: the same protocol used for A with 60 s of BH with face immersion in cold water during the first minute of PEMI. Stroke volume (SV), heart rate (HR), and cardiac output (CO) were collected by means of an impedance method.Results: At the end of apnea, HR was decreased in condition C and D with respect to A (−40.8 and −40.3%, respectively vs. −9.1%; p < 0.05). Since SV increase was less pronounced at the same time point (C = +32.4 and D = +21.7% vs. A = +6.0; p < 0.05), CO significantly decreased during C and D with respect to A (−23 and −29.0 vs. −1.4%, respectively; p < 0.05).Conclusion: Results addressed the hypothesis that DR overcame the MM in our setting.

Combined mental task and metaboreflex impair cerebral oxygenation in patients with type 2 diabetes mellitus.

Cardiovascular regulation is altered by type 2 diabetes mellitus (DM2), producing an abnormal response to muscle metaboreflex. During physical exercise, cerebral blood flow is impaired in patients with DM2, and this phenomenon may reduce cerebral oxygenation (COX). We hypothesized that the simultaneous execution of a mental task (MT) and metaboreflex activation would reduce COX in patients with DM2. Thirteen individuals suffering from DM2 (6 women) and 13 normal age-matched controls (CTL, 6 women) participated in this study. They underwent five different tests, each lasting 12 min: postexercise muscle ischemia (PEMI) to activate the metaboreflex, control exercise recovery (CER), PEMI+MT, CER+MT, and MT alone. COX was evaluated using near-infrared spectroscopy with sensors applied to the forehead. Central hemodynamics was assessed using impedance cardiography. We found that when MT was superimposed on the PEMI-induced metaboreflex, patients with DM2 could not increase COX to the same extent reached by the CTL group (101.13% ± 1.08% vs. 104.23% ± 2.51%, P < 0.05). Moreover, patients with DM2 had higher mean blood pressure and systemic vascular resistance as well as lower stroke volume and cardiac output levels compared with the CTL group, throughout our experiments. It was concluded that patients with DM2 had reduced capacity to enhance COX when undertaking an MT during metaboreflex. Results also confirm that patients with DM2 had dysregulated hemodynamics during metaboreflex, with exaggerated blood pressure response and vasoconstriction. This may have implications for these patients' lack of inclination to exercise.

Affective Variables and Cognitive Performances During Exercise in a Group of Adults With Type 2 Diabetes Mellitus.

Previous research has documented that type 2 diabetes mellitus (T2DM) is associated with cognitive impairment. Psychological variables were repeatedly investigated to understand why T2DM patients are poorly active, despite standards of medical care recommends performing aerobic and resistance exercise regularly and reducing the amount of time spent sitting. This exploratory study aims to investigate how affective variables as thoughts, feelings, and individuals’ stage of exercise adoption can modulate low cognitive performances during an experimental procedure based on exercise. The Exercise Thoughts Questionnaire (ETQ), Exercise-Induced Feeling Scale (EFI), and Physical Activity Stage of Change were administered to a sample of 12 T2DM patients. The Bivalent Shape Task (BST) alone (BST), BST with exercise [control exercise recovery (CER) + BST], and BST with metaboreflex [post-exercise muscle ischemia (PEMI) + BST] were used as mental task, and response time to congruent, incongruent, and neutral stimuli was recorded. Concomitant cerebral oxygenation (COX) was evaluated by near-infrared spectroscopy (NIRS). As expected, T2DM patients performed significantly better when the stimulus was presented in congruent trials (followed by neutral and incongruent). In the CER + BST session, T2DM patients showed longer reaction time to incongruent trials than in the PEMI + BST and BST alone sessions. Positive feelings toward exercise seem to modulate cognitive performances in high challenging task only if T2DM patients were conscious to play exercise. These results could provide some insights for health intervention targeting exercise for patients with T2DM in order to enhance cognitive performances.

A brief bout of exercise in hypoxia reduces ventricular filling rate and stroke volume response during muscle metaboreflex activation

PurposeThe hemodynamic consequences of exercise in hypoxia have not been completely investigated. The present investigation aimed at studying the hemodynamic effects of contemporary normobaric hypoxia and metaboreflex activation.MethodsEleven physically active, healthy males (age 32.7 ± 7.2 years) completed a cardiopulmonary test on an electromagnetically braked cycle-ergometer to determine their maximum workload (Wmax). On separate days, participants performed two randomly assigned exercise sessions (3 minutes pedalling at 30% of Wmax): (1) one in normoxia (NORMO), and (2) one in normobaric hypoxia with FiO2 set to 13.5% (HYPO). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia (PEMI) to study the metaboreflex, or (2) a control exercise recovery session, i.e., without metaboreflex activation. Hemodynamics were assessed with impedance cardiography.ResultsThe main result was that the HYPO session impaired the ventricular filling rate (measured as stroke volume/diastolic time) response during PEMI versus control condition in comparison to the NORMO test (31.33 ± 68.03 vs. 81.52 ± 49.23 ml·s−1,respectively, p = 0.003). This caused a reduction in the stroke volume response (1.45 ± 9.49 vs. 10.68 ± 8.21 ml, p = 0.020). As a consequence, cardiac output response was impaired during the HYPO test.ConclusionsThe present investigation suggests that a brief exercise bout in hypoxia is capable of impairing cardiac filling rate as well as stroke volume during the metaboreflex. These results are in good accordance with recent findings showing that among hemodynamic modulators, ventricular filling is the most sensible variable to hypoxic stimuli.

Effect of Combined Mental Task and Metaboreflex Activation on Hemodynamics and Cerebral Oxygenation in Patients With Metabolic Syndrome.

Objective: The hemodynamic response to muscle metaboreflex has been reported to be significantly altered by metabolic syndrome (MS), with exaggerated systemic vascular resistance (SVR) increments and reduced cardiac output (CO) in comparison to healthy controls (CTLs). Moreover, patients with metabolic disorders, such as type 2 diabetes, have proven to have impaired cerebral blood flow in response to exercise. Thus, we hypothesized that contemporary mental task (MT) and metaboreflex would result in reduced cerebral oxygenation (COX) in these patients.Methods: Thirteen MS patients (five women) and 14 normal age-matched CTLs (six women) were enrolled in this study. All the participants underwent five different tests, each lasting 12 min: post-exercise muscle ischemia (PEMI) to activate the metaboreflex, control exercise recovery (CER), PEMI + MT, CER + MT, and MT alone. Cerebral oxygenation was evaluated using near-infrared spectroscopy with sensors applied to the forehead. Hemodynamics were measured using impedance cardiography.Results: The main results show that MS patients had higher SVR and lower CO levels compared to the CTL group during metaboreflex activation. Stroke volume and ventricular filling and emptying rates were also significantly reduced. Moreover, when MT was added to PEMI, COX was significantly increased in the CTL group with respect to the baseline (103.46 ± 3.14%), whereas this capacity was reduced in MS patients (102.37 ± 2.46%).Conclusion: It was concluded that (1) patients with MS showed hemodynamic dysregulation during the metaboreflex, with exaggerated vasoconstriction and that (2) as compared to CTL, MS patients had reduced capacity to enhance COX when an MT superimposed the metaboreflex.

INTEGRATED EFFECTS OF NORMOBARIC HYPOXIA AND METABOREFLEX ACTIVATION ON HEMODYNAMICS

IntroductionBoth metaboreflex activity and hypoxia affect hemodynamics. In particular, metaboreflex induces an augmentation in stroke volume (SV), systemic vascular resistance (SVR), and blood pressure (BP) by activating the sympathetic nervous system (SNS). In contrast, hypoxia produces a heart rate (HR)‐mediated increase in cardiac output (CO), while its effect on SVR is variable as it increases SNS activity but, at the same time, it triggers nitric oxide (NO) production in the endothelium, thus inducing venous and arteriolar dilation. Since studies on the possible interaction between metaboreflex and hypoxia are still lacking, our investigation aimed to study their combined effects on hemodynamics.Methods11 male subjects underwent a preliminary cardiopulmonary exercise test (CPET) on a cycle ergometer to assess their aerobic fitness. Then, a metaboreflex activation protocol in normoxia and normobaric hypoxia (fraction of inspired oxygen – FiO2 – of 13.5%) was conducted on separate days. Hypoxia was induced using a hypoxic gas generator (Everest Summit II Generator, Hypoxico, USA) connected to the subjects by a facemask. The metaboreflex activation protocol consisted of two randomly assigned sessions: one of post‐exercise muscle ischemia (PEMI) and one of control exercise recovery (CER). PEMI comprised a 3‐minute exercise bout pedaling at 30% of the maximum workload reached during the CPET followed by 3 minutes of vascular occlusion using an inflatable thigh cuff to stimulate the metaboreflex. CER was similar, but no occlusion was applied after the exercise session. SV, HR, CO, ventricular filling rate (VFR), and ventricular ejection rate (VER) were measured through impedance cardiography while mean blood pressure (MBP) was assessed using manual sphygmomanometer. SVR was calculated indirectly from CO and MBP according to Poiseuille’s law. Near‐infrared spectroscopy was employed to measure cerebral oxygenation (COX) and peripheral hemoglobin saturation (SPO2) to control the level of tissue hypoxia. Two‐way ANOVA and paired sample t‐test were utilized when appropriate.ResultsCO was increased during metaboreflex activation in normoxia (p= 0.013) but not in hypoxia. SV, CO, and VFR responses to metaboreflex (measured as the difference PEMI‐CER at the third minute after exercise) were reduced when the hypoxic stimulus was applied (p=0.02; p=0.02; p=0.003 respectively). Moreover, SVR response showed a nearly significant (p=0.07) increase in hypoxia, with MBP response being unchanged. COX and SPO2 confirmed that the hypoxic stimulus was effective.DiscussionResults demonstrated that hypoxia impaired the hemodynamic response to metaboreflex. Specifically, SV was reduced during metaboreflex in hypoxia because of a reduction in preload as a consequence of two mechanisms: 1) a reduction in venous return probably induced by NO‐mediated vasodilation of the venous bed; 2) an increase in right ventricle afterload likely produced by the pulmonary arterial system vasoconstriction. Of note, baroreflex successfully defended MBP response despite the reduced CO during hypoxia.

METABOREFLEX ACTIVITY IN HEART FAILURE WITH REDUCED AND PRESERVED EJECTION FRACTION

IntroductionChronic heart failure (CHF) is a syndrome characterized by reduced cardiac output (CO) unable to meet metabolic demands of active tissues. The reduced (HFrEF) or preserved ejection fraction (HFpEF) identifies the systolic and diastolic HF respectively. Evidence has demonstrated that metabolic reflex coming from skeletal muscle evokes cardiovascular adjustments during exercise. Hemodynamic response to metaboreflex activation is defined as a rise in mean arterial blood pressure (MAP) achieved by an increase in systemic vascular resistance (SVR) and/or by an increase in CO. In healthy individuals, the metaboreflex‐induced increase in blood pressure mainly depends on CO increment. The aim of the present study was to assess cardiovascular adjustments during metaboreflex activation in both kinds of CHF patients compared to a control group of healthy individuals (CTL).MethodsThree groups of age‐matched subjects were studied: 1) 12 males patients diagnosed with HFrEF; 2) 8 males patients with diagnosed HFpEF; 3) 12 healthy individuals (CTL). All participants underwent a general medical examination, an incremental exercise test on a cycle ergometer to test their physical capacity, and a metaboreflex activation protocol consisting in a post exercise muscle ischemia (PEMI) and in a control exercise recovery (CER) session. All hemodynamic parameters were measured non‐invasively by impedance cardiography.ResultsStatistical analysis showed no differences in heart rate (HR) response among groups. Stroke volume (SV) and CO responses were not significantly different between the two groups of HF patients. SV and CO responses were significantly higher in the CTL than in both the HFrEF and the HFpEF group. SVR response was significantly higher in the HFrEF as compared to the CTL group, while no differences existed between the CTL and the HFpEF. MAP response to PEMI was not different among groups. Ventricular Filling Rate (VFR, a measure of diastolic function) response was significantly higher in CTL group in comparison with the HFrEF and the HFpEF groups. Ventricular Emptying Rate (VER, a measure of systolic function) response was significantly higher in CTL group as compared to the two groups of patients.ConclusionNotwithstanding the described reduced capacity to enhance CO, the MAP response was not different among groups. This indicates that the possibility to reach an effective MAP pressure was unaltered in both groups of patients with CHF. This was likely the consequence of an exaggerated vasoconstriction due to a sympathetic overdrive in both groups of CHF patients. These findings are in good agreement with previous research dealing with HFrEF and HFpEF, which demonstrated the blood pressure rise during the metaboreflex is mainly achieved by a vasoconstriction‐mediated rather than a flow‐mediated mechanism. Of note the SVR increase was more accentuated in the HFrEF than in the HFpEF group, and this phenomenon suggests that the cardiovascular impairment was more pronounced in the former than in the latter group of patients.

No effect of anti‐hypertensive treatment during the metaboreflex in patients with essential hypertension

In healthy subjects (HS), when the muscle metaboreflex (MM) is activated, the target mean blood pressure (MBP) is reached thanks to cardiac output (CO) increments, whilst systemic vascular resistance (SVR) plays a minor role 1. Differently, in essential hypertension (EHT) hemodynamics during the MM has been often reported to be dys‐regulated, with exaggerated SVR response (i.e. arteriolar vasoconstriction) and reduced CO 2. We tested the hypothesis that standard anti‐hypertensive treatment could improve this abnormal hemodynamics. 20 patients in pharmacological treatment for EHT (10 females; age 54.5±10.4 yrs, time since diagnosis 8.5±6.9 yrs) participated in this study together with a control group of 20 age‐matched HS. At baseline (BAS), they underwent randomly assigned the following protocol to study the MM activity: 1) post‐exercise muscle ischemia (PEMI), and 2) control exercise recovery CER) test. Exercise was dynamic handgrip performed at 30% of the maximum previously assessed. The EHT group performed again the test at least 7 days later (interval 7–15 days) after pharmacological wash‐out (WHT). Response to the MM for each cardiovascular parameter was assessed as PEMI minus CER level. Hemodynamic variables were evaluated by impedance cardiography. Results demonstrated that in EHT, SVR response did not change at the BAS and at the WHT (338.0±452.7 vs. 371.8±465.3 dynes•s‐1•cm‐5 at BAS and at WHT respectively). Moreover, EHT showed higher SVR response than HS (20.9±399.6 dynes•s‐1•cm‐5, p&lt;0.05 vs. both the BAS and the WHT test). However, the MBP response was similar between groups and conditions. Likewise CO was not different between groups. It was concluded that the anti‐hypertensive treatment was not able to counteract the arteriolar vasoconstriction and the increased SVR response experienced by ETH patients during the MM. Further study is warranted to better understand what causes the hemodynamic abnormalities of EHT patients during the MM activation.Support or Funding InformationThis study was supported by the University of Cagliari and the Italian Ministry of Scientific Research.

Effects of Metabolic Syndrome on Cognitive Performance of Adults During Exercise.

The metabolic syndrome (MS) has been associated with poor performances in multiple cognitive domains, as processing speed, visuo-spatial abilities, and executive functioning. Exercise is a critical factor for MS people’s vulnerability to cognitive dysfunction, because this may be beneficial to reduce cognitive impairment, but limited physical activity and impaired cerebral blood flow in response to exercise have been reported by individuals suffering from MS. Using an attentional interference test, the Bivalent Shape Task (BST), and metaboreflex, we analyzed cognitive performance and cerebral oxygenation (COX) in 13 MS people (five women), and 14 normal age-matched control (CTL, six women). Five different sessions were administered to all participants, each lasting 12 min: control exercise recovery (CER), post-exercise muscle ischemia (PEMI) to activate the metaboreflex, CER + BST, PEMI + BST, and BST alone. During each session, cognitive performance was assessed by means of response times and response accuracy with which participants make the decision and COX was evaluated by near infrared spectroscopy with sensors applied in the forehead. Compared to CTL, MS group performed significantly worse in all sessions (F = 4.18; p = 0.05; ES = 0.13): their poorest performance was observed in the BST alone session. Moreover, when BST was added to PEMI, individuals of the CTL group significantly increased their COX compared to baseline (103.46 ± 3.14%), whereas this capacity was impaired in MS people (102.37 ± 2.46%). It was concluded that: (1) MS affects cognitive performance; (2) people with MS were able to enhance COX during exercise, but they impair their COX when an attentional interference task was added.

Effects of exercise in normobaric hypoxia on hemodynamics during muscle metaboreflex activation in normoxia.

Little is known about the cardiovascular effects of the transition from exercise in hypoxia (EH) to normoxia. This investigation aimed to assess hemodynamics during the metaboreflex elicited in normoxia after EH. Ten trained athletes (four females and six males, age 35.6 ± 8.4years) completed a cardiopulmonary test to determine the workload at anaerobic threshold (AT). On separate days, participants performed three randomly assigned exercise sessions (10min pedalling at 80% of AT): (1) one in normoxia (EN); (2) one in normobaric hypoxia with FiO2 15.5% (EH15.5%); and (3) one in normobaric hypoxia with FiO2 13.5% (EH13.5%). After each session, the following protocol was randomly assigned: either (1) post-exercise muscle ischemia after cycling for 3min, to study the metaboreflex, or (2) a control exercise recovery (CER) session, without any metaboreflex stimulation. The main result were that both EH15.5% and EH13.5% impaired (p < 0.05) the ventricular filling rate response during the metaboreflex (- 18 ± 32 and - 20 ± 27mls-1), when compared to EN (+ 29 ± 32mls-1), thereby causing a reduction in stroke volume response (- 9.1 ± 3.2, - 10.6 ± 8.7, and + 5 ± 5.7ml for EH15.5%, EH13.5% and EN test, respectively, p < 0.05). Moreover, systemic vascular resistance was increased after the EH15.5% and the EH13.5% in comparison with the EN test. These data demonstrate that moderate exercise in hypoxia impairs the capacity to enhance venous return during the metaboreflex stimulated in normoxia. Overall, there is a functional shift from a flow to vasoconstriction-mediated mechanism for maintaining the target blood pressure during the metaboreflex.

Hemodynamic abnormalities during muscle metaboreflex activation in patients with type 2 diabetes mellitus.

Metaboreflex is a reflex triggered during exercise or postexercise muscle ischemia (PEMI) by metaboreceptor stimulation. Typical features of metaboreflex are increased cardiac output (CO) and blood pressure. Patients suffering from metabolic syndrome display hemodynamic abnormalities, with an exaggerated systemic vascular resistance (SVR) and reduced CO response during PEMI-induced metaboreflex. Whether patients with type 2 diabetes mellitus (DM2) have similar hemodynamic abnormalities is unknown. Here we contrast the hemodynamic response to PEMI in 14 patients suffering from DM2 (age 62.7 ± 8.3 yr) and in 15 age-matched controls (CTLs). All participants underwent a control exercise recovery reference test and a PEMI test to obtain the metaboreflex response. Central hemodynamics were evaluated by unbiased operator-independent impedance cardiography. Although the blood pressure response to PEMI was not significantly different between the groups, we found that the SVR and CO responses were reversed in patients with DM2 as compared with the CTLs (SVR: 392.5 ± 549.6 and -14.8 ± 258.9 dyn·s-1·cm-5; CO: -0.25 ± 0.63 and 0.46 ± 0.50 l/m, respectively, in DM2 and in CTL groups, respectively; P < 0.05 for both). Of note, stroke volume (SV) increased during PEMI in the CTL group only. Failure to increase SV and CO was the consequence of reduced venous return, impaired cardiac performance, and augmented afterload in patients with DM2. We conclude that patients with DM2 have an exaggerated vasoconstriction in response to metaboreflex activation not accompanied by a concomitant increase in heart performance. Therefore, in these patients, blood pressure response to the metaboreflex relies more on SVR increases rather than on increases in SV and CO. NEW & NOTEWORTHY The main new finding of the present investigation is that subjects with type 2 diabetes mellitus have an exaggerated vasoconstriction in response to metaboreflex activation. In these patients, blood pressure response to the metaboreflex relies more on systemic vascular resistance than on cardiac output increments.

Muscle metaboreflex activity after an acute session of exercise under hypoxia

In healthy subjects, when the muscle metaboreflex (MM) is activated, mean blood pressure (MBP) increases because of a sympathetic‐induced increase in both systemic vascular resistance (SVR) and cardiac output (CO)1. Acute hypoxia vasodilation has been often reported despite the increased sympathetic tone2. We hypothesized that a single session of exercise under normobaric hypoxia (ENH) resulted in an attenuation of the MBP increment during the muscle metaboreflex activated immediately after the ENH session. 10 well trained healthy male subjects (age 34.2±11.7 yrs) participated in this study. In separate days they underwent, randomly assigned, three exercise sessions consisting of 10 min pedaling at a workload corresponding to 80% of anaerobic threshold previously assessed. In one session (TEST21%) subjects breathed normoxic air (O2 21%), in the other two tests they breathed hypoxic air with O2 concentration of 16% (TEST16%) or 13% (TEST13%) respectively. Immediately after each exercise session they underwent randomly assigned the following protocol: 1) muscle metaboreflex activation obtained by the post‐exercise muscle ischemia (PEMI) method, and 2) control exercise recovery (CER) test. Response to the metaboreflex for each cardiovascular parameter was assessed as PEMI minus CER level. Hemodynamic parameters were evaluated by impedance cardiography. Results show that SVR response was reduced during the MM after the TST13% with respect to the other two tests (−46.5±394.2 vs. +108.9±256.3 and +213.6±228.8 dynes•s‐1•cm‐5 respectively, p&lt;0.05). However, the MBP response was similar between conditions. This because of an increased CO response which occurred during TEST13% in comparison with TEST21% and TEST16% (+421.3±545 vs. +63.2±322.9 and +128.3±238.6 ml respectively, p&lt;0.05). It was concluded that an acute session of exercise under hypoxia is able to reduce the capacity to vasoconstrict the vascular bed during the metaboreflex activation obtained by PEMI. However, mechanisms controlling cardiovascular responses successfully defended MBP response by increasing CO which compensated for the reduced SVR increment.Support or Funding InformationThis study was supported by the University of Cagliari and the Italian Ministry of Scientific Research.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Cerebral oxygenation in Metabolic Syndrome patients during mental task and muscle metaboreflex activation

The post‐exercise muscle ischemia (PEMI) is a well established method to study the cardiovascular adjustments to exercise since it enhances sympathetic tone thereby recruiting the hemodynamic reserves. Thus, PEMI can reveal cardiovascular diseases1,2. Our hypothesis was that, in patients suffering from Metabolic Syndrome (MS), cerebral oxygenation decreased during the metaboreflex elicited by PEMI, because of an exaggerated sympathetic response which could vasoconstrict the cerebral circulation3. Furthermore, we hypothesized that in these patients, the cerebral oxygenation could be further impaired by superimposing a mental task (MT) to PEMI. To this aim, variation in cerebral circulation of MS patients was compared with that of healthy controls during contemporary PEMI and MT.Two groups were enrolled: one composed of 15 subjects (7 women, age 53.5±10.7 yrs.) suffering from MS and a control group (CTL) composed of 14 healthy subjects (6 women, age 50.86±8.2 yrs). Both groups underwent 5 different tests each lasting 12 min: PEMI, control exercise recovery (CER), PEMI+MT, CER+MT, and MT alone. During each session, cerebral oxygenation (COx) was measured by Near Infrared Spectroscopy (NIRS) by applying sensors to the skin of the forehead.Data analysis found no significant differences in COx between groups during any test. No reduction in COx were observed during the PEMI test (CTL 100.9±3.3% vs MS 102.5±1.9%) and the MT test (CTL 101.5±2.2% vs MS 102±1.8%) in both groups. Moreover, the addiction of MT to the PEMI test did not cause any impairment in COx.Contrary to our hypothesis, results of the present study indicate that in patients with MS there is no impairment in COx during sympathetic activation obtained by PEMI. Furthermore, no significant reduction was found in the COx when adding MT to the PEMI test. It was concluded that COx is not impaired in patients suffering from MS when sympathetic tone is augmented.Support or Funding InformationThis study was supported by the “Fondazione di Sardegna”This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Metaboreflex-mediated hemodynamic abnormalities in individuals with coronary artery disease without overt signs or symptoms of heart failure.

This study was devised to investigate the effect of coronary artery disease (CAD) without overt signs of heart failure on the cardiovascular responses to muscle metaboreflex activation. We hypothesized that any CAD-induced preclinical systolic and/or diastolic dysfunction could impair hemodynamic response to the metaboreflex test. Twelve men diagnosed with CAD without any sign or symptoms of heart failure and 11 age-matched healthy control (CTL) subjects participated in the study. Subjects performed a postexercise muscle ischemia (PEMI) test to activate the metaboreflex. They also performed a control exercise recovery test to compare data from the PEMI test. The main results were that the CAD group reached a similar mean arterial blood pressure response as the CTL group during PEMI. However, the mechanism by which this response was achieved was different between groups. In particular, CAD achieved the target mean arterial blood pressure by increasing systemic vascular resistance (+383.8 ± 256.6 vs. +91.2 ± 293.5 dyn·s-1·cm-5 for the CAD and CTL groups, respectively), the CTL group by increasing cardiac preload (-0.92 ± 8.53 vs. 5.34 ± 4.29 ml in end-diastolic volume for the CAD and CTL groups, respectively), which led to an enhanced stroke volume and cardiac output. Furthermore, the ventricular filling rate response was higher in the CTL group than in the CAD group during PEMI ( P < 0.05 for all comparisons). This study confirms that diastolic function is pivotal for normal hemodynamics during the metaboreflex. Moreover, it provides evidence that early signs of diastolic impairment attributable to CAD can be detected by the metaboreflex test. NEW & NOTEWORTHY Individuals suffering from coronary artery disease without overt signs of heart failure may show early signs of diastolic dysfunction, which can be detected by the metaboreflex test. During the metaboreflex, these subjects show impaired preload and stroke volume responses and exaggerated vasoconstriction compared with controls.

Effects of Six Months Training on Physical Capacity and Metaboreflex Activity in Patients with Multiple Sclerosis.

Patients with multiple sclerosis (MS) have an increased systemic vascular resistance (SVR) response during the metaboreflex. It has been hypothesized that this is the consequence of a sedentary lifestyle secondary to MS. The purpose of this study was to discover whether a 6-month training program could reverse this hemodynamic dysregulation. Patients were randomly assigned to one of the following two groups: the intervention group (MSIT, n = 11), who followed an adapted training program; and the control group (MSCTL, n = 10), who continued with their sedentary lifestyle. Cardiovascular response during the metaboreflex was evaluated using the post-exercise muscle ischemia (PEMI) method and during a control exercise recovery (CER) test. The difference in hemodynamic variables such as stroke volume (SV), cardiac output (CO), and SVR between the PEMI and the CER tests was calculated to assess the metaboreflex response. Moreover, physical capacity was measured during a cardiopulmonary test till exhaustion. All tests were repeated after 3 and 6 months (T3 and T6, respectively) from the beginning of the study. The main result was that the MSIT group substantially improved parameters related to physical capacity (+5.31 ± 5.12 ml·min−1/kg in maximal oxygen uptake at T6) in comparison with the MSCTL group (−0.97 ± 4.89 ml·min−1/kg at T6; group effect: p = 0.0004). However, none of the hemodynamic variables changed in response to the metaboreflex activation. It was concluded that a 6-month period of adapted physical training was unable to reverse the hemodynamic dys-regulation in response to metaboreflex activation in these patients.

Metaboreflex Dysregulation In Type 2 Diabetes Mellitus

In healthy subjects, when the muscle metaboreflex (MM) is activated, mean blood pressure (MBP) increases because of a sympathetic-induced increase in both systemic vascular resistance (SVR) and cardiac output (CO)1. It has been reported that this reflex is dys-regulated in patients suffering some metabolic diseases. In detail, patients with type 1 diabetes mellitus (DM) have a blunted MBP response during the MM due to sympathetic deficit2; moreover, patients suffering from metabolic syndrome show an exaggerated SVR during the MM because of their sympathetic hyperactivation. PURPOSE: to discover whether the MM is dys-regulated is patients with type 2 DM. METHODS: 14 MS patients with type 2 DM obesity (4 females, 62.7±8.3 yrs) together with 13 control subjects (CTL, 5 females 61.2±10.5 yrs) participated in this study. They underwent randomly assigned the following protocol: 1) post-exercise muscle ischemia (PEMI) session, to study the MM, and 2) control exercise recovery (CER) session. Response to the metaboreflex for each cardiovascular parameter was assessed as PEMI minus CER level. Hemodynamic parameters were evaluated by impedance cardiography. RESULTS: patients with type 2 DM showed an exaggerated SVR response as compared to the CTL group (392.5±549.6, vs -68±248.5 dynes•s-1•cm-5 respectively, p<0.05), whereas MBP response was not different between groups (8.9±5.7 vs. 6.8±8.7 mmHg respectively, p>0.05). CONCLUSIONS: This investigation indicates that patients with type 2 DM have an exaggerated vasoconstriction in response to the MM activation. This phenomenon is different to what observed in type 1 DM2 and similar to what reported for metabolic syndrome3. 1 Crisafulli A et al. Muscle metaboreflex-induced increases in stroke volume. Med Sci Sports Exerc 2003; 35: 221-228. 2 Roberto S et al. Altered hemodynamics during muscle metaboreflex in young, type 1 diabetes patients. J Appl Physiol 2012; 113: 1323-1331. 3 Milia R et al. Differences in hemodynamic response to metaboreflex activation between obese patients with metabolic syndrome and healthy subjects with obese phenotype. Am J Physiol (Heart Circ Physiol) 2015; 309: H779-789.

Ischemic preconditioning reduces hemodynamic response during metaboreflex activation.

Ischemic preconditioning (IP) has been shown to improve exercise performance and to delay fatigue. However, the precise mechanisms through which IP operates remain elusive. It has been hypothesized that IP lowers the sensation of fatigue by reducing the discharge of group III and IV nerve endings, which also regulate hemodynamics during the metaboreflex. We hypothesized that IP reduces the blood pressure response during the metaboreflex. Fourteen healthy males (age between 25 and 48 yr) participated in this study. They underwent the following randomly assigned protocol: postexercise muscle ischemia (PEMI) test, during which the metaboreflex was elicited after dynamic handgrip; control exercise recovery session (CER) test; and PEMI after IP (IP-PEMI) test. IP was obtained by occluding forearm circulation for three cycles of 5 min spaced by 5 min of reperfusion. Hemodynamics were evaluated by echocardiography and impedance cardiography. The main results were that after IP the mean arterial pressure response was reduced compared with the PEMI test (means ± SD +3.37 ± 6.41 vs. +9.16 ± 7.09 mmHg, respectively). This was the consequence of an impaired venous return that impaired the stroke volume during the IP-PEMI more than during the PEMI test (-1.43 ± 15.35 vs. +10.28 ± 10.479 ml, respectively). It was concluded that during the metaboreflex, IP affects hemodynamics mainly because it impairs the capacity to augment venous return and to recruit the cardiac preload reserve. It was hypothesized that this is the consequence of an increased nitric oxide production, which reduces the possibility to constrict venous capacity vessels.

Metaboreflex activity in multiple sclerosis patients.

The muscle metaboreflex activation has been shown essential to reach normal hemodynamic response during exercise. It has been demonstrated that patients with multiple sclerosis (MS) have impaired autonomic functions and cardiovascular regulation during exercise. However, to the best of our knowledge, no previous research to date has studied the metaboreflex in MS patients. The purpose of this study was to investigate the hemodynamic response to metaboreflex activation in patients with MS (n = 43) compared to an age-matched, control group (CTL, n = 21). Cardiovascular response during the metaboreflex was evaluated using the post-exercise muscle ischemia (PEMI) method and during a control exercise recovery (CER) test. The difference in hemodynamics between the PEMI and the CER test was calculated and this procedure allowed for the assessment of the metaboreflex response. Hemodynamics was estimated by impedance cardiography. The MS group showed a normal mean blood pressure (MBP) response as compared to the CTL group (+6.5 ± 6.9 vs. +8 ± 6.8 mmHg, respectively), but this response was achieved with an increase in systemic vascular resistance, that was higher in the MS with respect to the CTL group (+137.6 ± 300.5 vs. -14.3 ± 240 dyne · s(-1) cm(-5), respectively). This was the main consequence of the MS group's incapacity to raise the stroke volume (-0.65 ± 10.6 vs. +6.2 ± 12.8 ml, respectively). It was concluded that MS patients have an impaired capacity to increase stroke volume (SV) in response to low level metaboreflex, even if they could sustain the MBP response by vasoconstriction. This was probably a consequence of their chronic physical de-conditioning.

Altered Metaboreflex Activity In Patients With Metabolic Syndrome

In healthy individuals, activation of the muscle metaboreflex leads to increase in mean blood pressure (MBP) due to increase in both systemic vascular resistance (SVR) and cardiac output (CO)1. It has been reported that patients suffering from metabolic syndrome (MS) have a dysregulation of this reflex with an exaggerated SVR increase with respect to normal controls2. However, it is not clear whether this is the consequence of MS per se or this is due to concomitant obesity (OB). PURPOSE: to discover whether MS and OB had different hemodynamic response during the metaboreflex. METHODS: 13 MS patients with obesity (5 females, 50.3±16.3 yrs, body mass index 32.1±4.4), 11 patients with OB without MS (6 females, 38.4±10.1 yrs, body mass index 34.6±5.7) together with 12 control subjects (CTL, 6 females 41±10.5 yrs, body mass index 21.5±2.5) took part in this study. Each individual underwent randomly assigned the following protocol: 1) post-exercise muscle ischemia (PEMI) session, to study the metaboreflex, and 2) control exercise recovery (CER) session. Response to the metaboreflex for each cardiovascular parameter was assessed as PEMI-CER level. Central hemodynamics were evaluated by means of impedance cardiography. RESULTS: the main result was that patients with MS had an exaggerated SVR response with respect to the OB and the CTL group (481.6±595.3, -0.52±376.6, and 130.4±373.7 dynes•s-1•cm-5 for the MS, the OB, and the CTL group respectively, p<0.05), whereas MBP response was not different between groups (10.2±5.6, 8.3±8.6, and 6.05±8.6 mmHg for the MS, the OB, and the CTL group respectively, p>0.05). CONCLUSIONS: This investigation demonstrates that patients with obesity and metabolic syndrome show an exaggerated vasoconstriction in response to metaboreflex activation. This fact was not present in OB without MS. Thus, it is not obesity per se to dysregulate hemodynamics during the metaboreflex. REFERENCES 1 Crisafulli A et al. Muscle metaboreflex-induced increases in stroke volume. Med Sci Sports Exerc 2003; 35: 221-228. 2 Limberg J et al. Mechanical and metabolic reflex activation of the sympathetic nervous system in younger adults with metabolic syndrome. Aut Neurosci 2014 (at press).

Effects of acute vasodilation on the hemodynamic response to muscle metaboreflex

The aim of the present study was to test the contribution of stroke volume (SV) in hemodynamic response to muscle metaboreflex activation in healthy individuals. We hypothesized that an acute decrease in cardiac afterload and preload due to the administration of a vasodilating agent could reduce postexercise muscle ischemia (PEMI)-induced SV response. Ten healthy males (age 33.6 ± 1.3 yr) were enrolled and randomly assigned to the following study protocol: 1) PEMI session, 2) control exercise recovery (CER) session, 3) PEMI after sublingual administration of 5 mg of isosorbide dinitrate (ISDN), and 4) CER after ISDN. Central hemodynamics were evaluated by means of impedance cardiography. The main findings were a blunted SV response during metaboreflex following acute arterial and venous vasodilation, associated with a reduction in cardiac diastolic time and filling, and a decrement of systemic vascular resistance. These hemodynamic changes restrain blood pressure response during metaboreflex activation. Our results indicate that hemodynamic response to metaboreflex activation is a highly integrated phenomenon encompassing complex interplay between heart rate, cardiac performance, preload, and afterload and that impairment of one or more of these parameters leads to altered hemodynamic response to metaboreflex.