L-Citrulline Supplementation Improves Arterial Blood Flow and Muscle Oxygenation during Handgrip Exercise in Hypertensive Postmenopausal Women.

Endothelial dysfunction decreases exercise limb blood flow (BF) and muscle oxygenation. Acute L-Citrulline supplementation (CIT) improves muscle tissue oxygen saturation index (TSI) and deoxygenated hemoglobin (HHb) during exercise. Although CIT improves endothelial function (flow-mediated dilation [FMD]) in hypertensive women, the impact of CIT on exercise BF and muscle oxygenation (TSI) and extraction (HHb) are unknown. We examined the effects of CIT (10 g/day) and a placebo for 4 weeks on blood pressure (BP), arterial vasodilation (FMD, BF, and vascular conductance [VC]), and forearm muscle oxygenation (TSI and HHb) at rest and during exercise in 22 hypertensive postmenopausal women. Compared to the placebo, CIT significantly (p < 0.05) increased FMD (Δ-0.7 ± 0.6% vs. Δ1.6 ± 0.7%) and reduced aortic systolic BP (Δ3 ± 5 vs. Δ-4 ± 6 mmHg) at rest and improved exercise BF (Δ17 ± 12 vs. Δ48 ± 16 mL/min), VC (Δ-21 ± 9 vs. Δ41 ± 14 mL/mmHg/min), TSI (Δ-0.84 ± 0.58% vs. Δ1.61 ± 0.46%), and HHb (Δ1.03 ± 0.69 vs. Δ-2.76 ± 0.77 µM). Exercise BF and VC were positively correlated with improved FMD and TSI during exercise (all p < 0.05). CIT improved exercise artery vasodilation and muscle oxygenation via increased endothelial function in hypertensive postmenopausal women.

Prevalence, mechanisms, and prognostic impact of dynamic mitral regurgitation assessed by isometric handgrip exercise.

AIMS: The extent of mitral regurgitation (MR) may vary depending on the haemodynamic situation; thus, exercise testing plays an important role in assessing the haemodynamic relevance of MR. We aim to assess prevalence, mechanisms, and prognostic impact of exercise-induced changes in MR in patients with degenerative MR (DegMR) and functional MR (FMR). METHODS AND RESULTS: We enrolled 367 patients with at least mild MR who underwent standardized echocardiography at rest and during handgrip exercise. Handgrip exercise led to an increase in MR by one grade or more in 19% of DegMR and 28% of FMR patients. In FMR, patients with exercise-induced increases in MR, handgrip exercise led to a reduction in left ventricular stroke volume index, being maintained in DegMR patients. Exercise-induced changes in systolic pulmonary artery pressure were linked to changes in effective regurgitant orifice area (DegMR: r = 0.456; P < 0.001; FMR: r = 0.326; P < 0.001). Thus, 26% of patients with DegMR and FMR developed pulmonary hypertension during exercise. In both cohorts, a significant proportion of patients with non-severe MR at rest and exercise-induced severe MR underwent mitral valve surgery/intervention during follow-up. In FMR patients (but not in DegMR patients), early mitral valve surgery/intervention was independently associated with lower event rates during follow-up [0.177 (0.027-0.643); P = 0.025]. CONCLUSIONS: Handgrip exercise echocardiography provides important information regarding the dynamic nature of MR, exercise-induced changes in left ventricular function, and pulmonary circulation with subsequent consequences for further therapeutic decision making. Thus, it should be considered as a diagnostic tool in symptomatic patients with non-severe MR at rest.

Obesity does not alter vascular function and handgrip exercise hemodynamics in middle-aged patients with hypertension.

Lifestyle modification including exercise training is often the first line of defense in the treatment of obesity and hypertension (HTN), however, little is known regarding how these potentially compounding disease states impact vasodilatory and hemodynamic responses at baseline and exercise. Therefore, this study sought to compare the impact of obesity on vascular function and hemodynamics at baseline and during handgrip (HG) exercise among individuals with HTN. Non-obese (13M/7F, 56 ± 16 yr, 25 ± 4 kg/m2) and obese (17M/4F, 50 ± 7 yr, 35 ± 4 kg/m2) middle-aged individuals with HTN forwent antihypertensive medication use for ≥2 wk before assessment of vascular function by brachial artery flow-mediated dilation (FMD) and exercise hemodynamics during progressive HG exercise at 15-30-45% maximal voluntary contraction (MVC). FMD was not different between Non-Obese (4.1 ± 1.7%) and Obese (5.2 ± 1.9%, P = 0.11). Systolic blood pressure (SBP) was elevated by ∼15% during the supine baseline and during HG exercise in the obese group. The blood flow response to HG exercise at 30% and 45% MVC was ∼20% greater (P < 0.05) in the obese group but not different after normalizing for the higher, albeit, nonsignificant differences in workloads (MVC: obese: 24 ± 5 kg, non-obese: 21 ± 5 kg, P = 0.11). Vascular conductance and the brachial artery shear-induced vasodilatory response during HG were not different between groups (P > 0.05). Taken together, despite elevated SBP during HG exercise, obesity does not lead to additional impairments in vascular function and peripheral exercising hemodynamics in patients with HTN. Obesity may not be a contraindication when prescribing exercise for the treatment of HTN among middle-aged adults, however, the elevated SBP should be appropriately monitored.NEW & NOTEWORTHY This study examined vascular function and handgrip exercise hemodynamics in obese and nonobese individuals with hypertension. Obesity, when combined with hypertension, was neither associated with additional vascular function impairments at baseline nor peripheral hemodynamics and vasodilation during exercise compared with nonobese hypertension. Interestingly, systolic blood pressure and pulse pressure were greater in the obese group during supine baseline and exercise. These findings should not be ignored and may be particularly important for rehabilitation strategies.

Handgrip exercise in patients scheduled for cardiac surgery to attenuate troponin release: a feasibility study.

Cardiac surgery, including surgical aortic valve repair (SAVR) and coronary artery bypass grafting (CABG), are associated with ischemia-reperfusion (I/R) injury. Single bouts of exercise, including handgrip exercise, may protect against I/R injury. This study explored 1) the feasibility of daily handgrip exercise in the week before SAVR and/or CABG and 2) its impact on cardiac I/R injury, measured as postoperative cardiac troponin-T (cTnT) release. Sixty-five patients undergoing elective SAVR and/or CABG were randomized to handgrip exercise + usual care (intervention, n = 33) or usual care alone (control, n = 32). Handgrip exercise consisted of daily 4 × 5-min handgrip exercise (30% maximal voluntary contraction) for 2-7 days before cardiac surgery. Feasibility was assessed using validated questionnaires. Postoperative cTnT release was assessed at 0, 6, 12, 18, and 24 h [primary outcome area under the curve (cTnTAUC)]. Most patients (93%) adhered to handgrip exercise and 77% was satisfied with this intervention. Handgrip exercise was associated with lower cTnTAUC (402,943 ± 225,206 vs. 473,300 ± 232,682 ng · min/L), which is suggestive of a medium effect size (Cohen's d 0.31), and lower cTnTpeak (313 [190-623] vs. 379 [254-699] ng/L) compared with controls. We found that preoperative handgrip exercise is safe and feasible for patients scheduled for SAVR and/or CABG and is associated with a medium effect size to reduce postoperative cardiac I/R injury. This warrants future studies to assess the potential clinical impact of exercise protocols before cardiac surgery.NEW & NOTEWORTHY Daily handgrip exercise in the week before elective cardiac surgery is safe and feasible. Handgrip exercise is associated with a medium effect size for less troponin-T release. Future larger-sized studies are warranted to explore the impact of (handgrip) exercise prior to cardiac surgery on clinical outcomes and direct patient benefits.

Baroreflex resetting of human sympathetic action potential subpopulations during exercise.

This study tested the hypothesis that during fatiguing volitional exercise in humans, descending cortical signals and ascending skeletal muscle metaboreflex signals exert divergent control over baroreflex resetting of sympathetic action potential (AP) discharge. We quantified the baroreflex gain for sympathetic AP clusters within the muscle sympathetic nerve activity neurogram (peroneal microneurography and continuous wavelet transform) during baseline (BSL), the first 2-min of a 5-min isometric handgrip (20% of maximal effort; IHG1), the last 2-min of IHG (IHG2), and during postexercise circulatory occlusion (PECO) in seven healthy participants. AP baroreflex threshold gain was measured as the slope of the linear relationship between AP probability (%) versus diastolic blood pressure (DBP; mmHg) for 10 normalized AP clusters. Compared with BSL, during IHG1, AP baroreflex threshold functions were only reset to greater DBP and baroreflex gain was unaffected. Compared with BSL, during IHG2 and PECO, baroreflex functions were reset to greater DBP and to greater AP firing probabilities, with medium-sized APs demonstrating the largest upward resetting (e.g., cluster 3 BSL: 26 ± 7%, cluster 3 IHG2: 78 ± 22%, cluster 3 PECO: 88 ± 46%). Compared with BSL, AP baroreflex threshold gain was not different during IHG2 but was increased during PECO, with medium-sized APs demonstrating the largest increase in baroreflex gain (e.g., cluster 3 BSL: -6.31 ± 3.1%/mmHg, cluster 3 IHG2: -6.18 ± 5.4%/mmHg, cluster 3 PECO: -12.13 ± 6.5%/mmHg). These findings indicate that during IHG exercise, descending cortical signaling and ascending skeletal muscle metaboreceptor signals differentially affect baroreflex resetting of subpopulations of human muscle sympathetic postganglionic neurons.NEW & NOTEWORTHY This study provides new insight to baroreflex resetting of MSNA during exercise in humans. Both fatiguing IHG and PECO reset baroreflex control of sympathetic APs to higher blood pressures and greater MSNA. However, only PECO increased baroreflex threshold gain of medium-sized sympathetic APs, an effect that was concealed when focusing on the integrated MSNA neurogram to quantify baroreflex gain. These data suggest that descending central versus ascending muscle metaboreflex mechanisms differentially affect baroreflex resetting of sympathetic APs.

The role of HIV as a risk modifier for coronary endothelial function in young adults.

BACKGROUND: People living with HIV have an increased risk of cardiovascular disease (CVD). Although coronary endothelial function (CEF) is an early direct indicator of CVD, only a few studies have been able to interrogate CEF directly. Most studies have examined vascular endothelial function through indirect assessment of brachial flow-mediated dilatation (FMD). However, peripheral arteries are significantly larger and manifest atherogenesis differently from the coronary arteries, and so produce conflicting results. Additionally, none of these studies focused on young adults who acquired HIV perinatally or in early childhood. OBJECTIVE: The present study investigates CEF in a unique population of young adults with lifelong HIV using direct magnetic resonance imaging (MRI) of coronary FMD (corFMD) with an in-house developed MRI-integrated isometric handgrip exercise system with continuous feedback and monitoring mechanisms (fmIHE). METHODS: Young adults who acquired HIV perinatally or in early childhood (n = 23) and group-matched healthy participants (n = 12) completed corFMD-MRI with fmIHE. CorFMD was measured as the coronary cross-sectional area response to the fmIHE. RESULTS: In univariable and multivariable regression analysis, HIV status was a significant risk modifier. CD8+ T-cell count and smoking pack-years and their interaction with HIV status were independently associated with impaired coronary artery response to fmIHE. In people living with HIV, corFMD was significantly inversely correlated with CD8+ T-cells and smoking pack-years. In a multivariable regression analysis adjusted for age and body mass index, CD8+ T-cells and smoking and their interaction with HIV status remained significant independent predictors of coronary endothelial dysfunction. DISCUSSION: In this unique population of young adults, HIV status was a significant risk modifier, and immune activation and smoking were associated with decreased CEF, directly measured from the coronary vascular response to fmIHE. CONCLUSIONS: Management of CVD risk factors such as smoking and developing strategies that target immune activation in people living with HIV are warranted.

Assessment of baroreflex sensitivity during isometric handgrip exercise and oscillatory lower body negative pressure.

Objectives: Baroreflex sensitivity (BRS) is an estimate of autonomic control of cardiovascular system via the baroreflex arc. It has been suggested that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain, which facilitates the simultaneous rise in blood pressure (BP) and heart rate during the exercise. This study investigated the effects of isometric handgrip exercise (IHE) on baroreflex gain and frequency dependence of baroreflex sensitivity while fluctuations in arterial BP were generated. Methods: Thirteen healthy men performed IHE at 20% and 30% of their maximum voluntary contraction (MVC), while oscillatory lower body negative pressure (OLBNP) of 40 mmHg was applied in 0.1 and 0.25 Hz frequencies. Results: Compared to the OLBNP at 0.25 Hz frequency alone, the baroreflex gain for diastolic BP (DBP) was significantly reduced with the addition of IHE at 20% and 30% of MVC in the high frequency band. At rest (without IHE and OLBNP) the baroreflex gain was significantly more in the high frequency band for DBP, but the baroreflex gain for DBP was not significantly different when IHE + OLBNP were applied at 20% and 30% of MVC in both frequencies. Conclusions: The significant reduction of DBP baroreflex gain with the addition of graded IHE might indicate that exercise pressure reflex and muscle metaboreflex override baroreflex during exercise to decrease baroreflex gain at a high frequency band (0.25 Hz). The frequency-dependent phenomenon of BRS was altered when IHE and OLBNP were applied, meaning that the frequency dependence of BRS was nullified during IHE.

Muscle Oxygenation and Microvascular Reactivity Across Different Stages of CKD: A Near-Infrared Spectroscopy Study.

RATIONALE & OBJECTIVE: Previous studies in chronic kidney disease (CKD) showed that vascular dysfunction in different circulatory beds progressively deteriorates with worsening CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with different stages of CKD versus controls. STUDY DESIGN: Observational controlled study. SETTING & PARTICIPANTS: 90 participants (18 per CKD stage 2, 3a, 3b, and 4, as well as 18 controls). PREDICTOR: CKD stage. OUTCOME: The primary outcome was muscle oxygenation at rest. Secondary outcomes were muscle oxygenation during occlusion-reperfusion and exercise, and muscle microvascular reactivity (hyperemic response). ANALYTICAL APPROACH: Continuous measurement of muscle oxygenation [tissue saturation index (TSI)] using near-infrared spectroscopy at rest, during occlusion-reperfusion, and during a 3-minute handgrip exercise (at 35% of maximal voluntary contraction). Aortic pulse wave velocity and carotid intima-media thickness were also recorded. RESULTS: Resting muscle oxygenation did not differ across the study groups (controls: 64.3% ± 2.9%; CKD stage 2: 63.8% ± 4.2%; CKD stage 3a: 64.1% ± 4.1%; CKD stage 3b: 62.3% ± 3.3%; CKD stage 4: 62.7% ± 4.3%; P=0.6). During occlusion, no significant differences among groups were detected in the TSI occlusion magnitude and TSI occlusion slope. However, during reperfusion the maximum TSI value was significantly lower in groups of patients with more advanced CKD stages compared with controls, as was the hyperemic response (controls: 11.2%±3.7%; CKD stage 2: 8.3%±4.6%; CKD stage 3: 7.8%±5.5%; CKD stage 3b: 7.3%±4.4%; CKD stage 4: 7.2%±3.3%; P=0.04). During the handgrip exercise, the average decline in TSI was marginally lower in patients with CKD than controls, but no significant differences were detected across CKD stages. LIMITATIONS: Moderate sample size, cross-sectional evaluation. CONCLUSIONS: Although no differences were observed in muscle oxygenation at rest or during occlusion, the microvascular hyperemic response during reperfusion was significantly impaired in CKD and was most prominent in more advanced CKD stages. This impaired ability of microvasculature to respond to stimuli may be a crucial component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance. PLAIN-LANGUAGE SUMMARY: Previous studies in chronic kidney disease (CKD) have shown that vascular dysfunction in different circulatory beds progressively deteriorates with CKD severity. This study evaluated muscle oxygenation and microvascular reactivity at rest, during an occlusion-reperfusion maneuver, and during exercise in patients with nondialysis CKD versus controls, as well as across different CKD stages. It showed that the microvascular hyperemic response after an arterial occlusion was significantly impaired in CKD and was worst in patients with more advanced CKD. No significant differences were detected in skeletal muscle oxygenation or muscle oxidative capacity at rest or during the handgrip exercise when comparing patients with CKD with controls or comparing across CKD stages. The impaired ability of microvasculature to respond to stimuli may be a component of the adverse vascular profile of patients with CKD and may contribute to exercise intolerance.

Left Ventricular Diastolic Response to Isometric Handgrip Exercise in Physically Active and Sedentary Individuals.

Aims: This study aims to investigate the diastolic left ventricular (LV) response to isometric handgrip exercise among healthy middle-aged men with high physical activity levels, versus matched sedentary individuals. Methods: Two groups of 10 men aged 41−51 years were studied. Men in the first group had high weekly self-reported physical activity levels (>3000 METs × min/week). In comparison, men in the second group reported low physical activity levels (<300 METs × min/week). An isometric handgrip exercise (IHE) stress echocardiography test was performed in all of them. Results: Both groups showed a similar and statistically significant increase in heart rate, systolic, diastolic, and mean arterial pressure following IHE. The group of active men under study did not show a statistically significant change in the ratio of early diastolic mitral valve inflow velocity to early diastolic lateral wall tissue velocity (E/e' ratio) in response to IHE. Conversely, the inactive participants' E/e' ratio was higher at peak activity in the isometric handgrip exercise. Conclusions: Apparently, healthy middle-aged men with high levels of physical activity seem to have an improved lusitropic cardiac function compared to men with low levels of physical activity, as observed by the different diastolic LV responses induced by isometric handgrip exercise.

Matching of O2 Utilization and O2 Delivery in Contracting Skeletal Muscle in Health, Aging, and Heart Failure.

Skeletal muscle is one of the most dynamic metabolic organs as evidenced by increases in metabolic rate of >150-fold from rest to maximal contractile activity. Because of limited intracellular stores of ATP, activation of metabolic pathways is required to maintain the necessary rates of ATP re-synthesis during sustained contractions. During the very early phase, phosphocreatine hydrolysis and anaerobic glycolysis prevails but as activity extends beyond ∼1 min, oxidative phosphorylation becomes the major ATP-generating pathway. Oxidative metabolism of macronutrients is highly dependent on the cardiovascular system to deliver O2 to the contracting muscle fibres, which is ensured through a tight coupling between skeletal muscle O2 utilization and O2 delivery. However, to what extent O2 delivery is ideal in terms of enabling optimal metabolic and contractile function is context-dependent and determined by a complex interaction of several regulatory systems. The first part of the review focuses on local and systemic mechanisms involved in the regulation of O2 delivery and how integration of these influences the matching of skeletal muscle O2 demand and O2 delivery. In the second part, alterations in cardiovascular function and structure associated with aging and heart failure, and how these impact metabolic and contractile function, will be addressed. Where applicable, the potential of exercise training to offset/reverse age- and disease-related cardiovascular declines will be highlighted in the context of skeletal muscle metabolic function. The review focuses on human data but also covers animal observations.

Inorganic nitrate supplementation and blood flow restricted exercise tolerance in post-menopausal women.

Exercise tolerance appears to benefit most from dietary nitrate (NO3-) supplementation when muscle oxygen (O2) availability is low. Using a double-blind, randomized cross-over design, we tested the hypothesis that acute NO3- supplementation would improve blood flow restricted exercise duration in post-menopausal women, a population with reduced endogenous nitric oxide bioavailability. Thirteen women (57-76 yr) performed rhythmic isometric handgrip contractions (10% MVC, 30 per min) during progressive forearm blood flow restriction (upper arm cuff gradually inflated 20 mmHg each min) on three study visits, with 7-10 days between visits. Approximately one week following the first (familiarization) visit, participants consumed 140 ml of NO3- concentrated (9.7 mmol, 0.6 gm NO3-) or NO3-depleted beetroot juice (placebo) on separate days (≥7 days apart), with handgrip exercise beginning 100 min post-consumption. Handgrip force recordings were analyzed to determine if NO3- supplementation enhanced force development as blood flow restriction progressed. Nitrate supplementation increased plasma NO3- (16.2-fold) and NO2- (4.2-fold) and time to volitional fatigue (61.8 ± 56.5 s longer duration vs. placebo visit; p = 0.03). Nitrate supplementation increased the rate of force development as forearm muscle ischemia progressed (p = 0.023 between 50 and 75% of time to fatigue) with non-significant effects thereafter (p = 0.052). No effects of nitrate supplementation were observed for mean duration of contraction or relaxation rates (all p > 0.150). These results suggest that acute NO3- supplementation prolongs time-to-fatigue and speeds grip force development during progressive forearm muscle ischemia in postmenopausal women.

Immune system response to isometric handgrip exercise and effects of duration and intensity of the exercise protocol on selected immune system parameters in prehypertensives.

BACKGROUND: Recent studies have shown that physical exercise significantly modulates immunocyte dynamics and possibly plays a significant role on immune function. This study examined the responses of some selected immune system parameters to isometric handgrip exercise and identified possible effects of intensity and duration of the exercise protocols. METHODS: One hundred and ninety-two (N=192) sedentary pre-hypertensive subjects, aged between 30-50 years were recruited into the study. They were randomly distributed into three groups of 64 subjects each. A detailed explanation and a demonstration of the exercise protocol were given to the subjects and they were asked to report at the Exercise Physiology unit of the Physiotherapy department, Federal Medical Centre, Asaba, Delta State at 4.00 pm daily for the exercise practice. The training session for each day took place between the hours of 4.00 pm and 8.00 pm daily (FMC/ASB/A81.VOL.XII/101). The subjects performed a 24 consecutive day's isometric handgrip exercise at 30% Maximum Voluntary Contraction (MVC). At the end of the 24 days, group one (GP1) discontinued with the exercise protocol, while group two (GP2) and group three (GP3) continued with the exercise protocol for another 24 consecutive days nevertheless GP3 performed at an increased intensity of 50% MVC. The clinical trial was registered with Nigeria Clinical Trial Registry, Federal Ministry of Health, Abuja Nigeriawith Trial No: 1216582 (https://www.nctr.nhrec.net/viewTrials.php?TID=1216582). RESULTS: At the end of the study, the result shows thatthe number of CD4 cells and CD4/CD8 ratio significantly (P<0.05) increased while the CD8 cell decreased in GP2 and GP3. It was further shown that increase in duration produced a more significant change compared to an increase in intensity of the isometric effort. CONCLUSION: The study established that isometric handgrip exercise alters the circulating levels of the immune system parameters which could have positive beneficial effects on the prehypertensive individuals as the number of CD4 cells and CD4/CD8 ratio increased especially when practiced over a longer duration.

Site-specific different dynamic cerebral autoregulation and cerebrovascular response to carbon dioxide in posterior cerebral circulation during isometric exercise in healthy young men.

Different cerebral blood flow (CBF) responses to exercise between the posterior cerebral artery (PCA) and vertebral artery (VA) have been previously observed, though the physiological mechanisms remain unknown. There is regional heterogeneity in sympathetic innervation between the PCA and VA, which may affect CBF regulation, especially during sympathoexcitation. Thus, in the present study, we hypothesized that different CBF regulatory mechanisms between PCA and VA contribute to heterogeneous CBF responses to isometric exercise. To test this hypothesis, in thirteen healthy young men, dynamic cerebral autoregulation (CA) and cerebrovascular CO2 reactivity (CVR), were identified in each artery during a 2-min isometric handgrip (IHG) exercise at 30% of maximum voluntary contraction. Similar to previous data, PCA cerebrovascular conductance (CVC) index was decreased from rest (P < 0.004), but not VA CVC during IHG exercise (P > 0.084). Dynamic CA in both PCA and VA were unaltered during the IHG exercise (P = 0.129). On the other hand, PCA CVR was increased during the IHG exercise (P < 0.001) while VA CVR was unchanged (P = 0.294). In addition, individual exercise-induced changes in end-tidal partial pressure of CO2 was related to the individual change in PCA blood velocity (P < 0.046), but was not observed for VA blood flow (P > 0.420). Therefore, these exercise-induced differences in CVR between PCA and VA may contribute to exercise-induced heterogeneous CBF response in the posterior cerebral circulation. These findings indicate that the site-specific posterior CBF should be considered in further research for assessing posterior cerebral circulation.

Effect of breath-hold on the responses of arterial blood pressure and cerebral blood velocity to isometric exercise.

PURPOSE: The present study examined the effect of breath-hold without a Valsalva maneuver during isometric exercise on arterial blood pressure (ABP) and cerebral blood flow (CBF). METHODS: Twenty healthy adults (15 men and five women) randomly performed only breath-hold without a Valsalva maneuver (BH), and an isometric handgrip exercise for 30 s at 40% of individual maximal voluntary contraction with continuous breathing (IHG) and with breath-hold without the Valsalva maneuver (IHG-BH). Mean ABP (MAP) and blood velocity in the middle (MCA Vmean) and posterior cerebral arteries (PCA Vmean) were continuously measured throughout each protocol. RESULTS: MAP was elevated during the IHG-BH compared with IHG (P < 0.001) and BH (P = 0.001). Similarly, both MCA Vmean and PCA Vmean were higher during IHG-BH compared with IHG and BH (all P < 0.001). Moreover, the relative change in MAP from the baseline was correlated with that in both cerebral blood velocities during the BH (MCA Vmean: r = 0.739, P < 0.001 and PCA Vmean: r = 0.570, P = 0.009) and IHG-BH (MCA Vmean: r = 0.755, P < 0.001 and PCA Vmean: r = 0.617, P = 0.003) condition, but not the IHG condition (P = 0.154 and P = 0.306). CONCLUSION: These results indicate that during isometric exercise, a breath-hold enhances an exercise-induced increase in MAP and, consequently, MCA Vmean and PCA Vmean.

CMR detects decreased myocardial deformation in asymptomatic patients at risk for heart failure.

Aims: The main management strategy of heart failure with preserved ejection fraction (HFpEF) is prevention since HFpEF is associated with many cardiovascular (CV) risk factors, especially since HFpEF is linked to a high risk for both mortality and recurrent heart failure (HF) hospitalizations. Therefore, there is a need for new tools to identify patients with a high risk profile early. Regional strain assessment by CMR seems to be superior in describing deformation impairment in HF. The MyoHealth score is a promising tool to identify cardiac changes early. Methods and results: Heart failure patients irrespective of LVEF and asymptomatic controls were recruited, and CMR based measures were obtained. For this analysis the asymptomatic control group (n = 19) was divided into asymptomatic subjects without CV co-morbidities or evidence of cardiac abnormalities and (n = 12) and asymptomatic subjects with CV co-morbidities or evidence of cardiac abnormalities (n = 7) as well as patients with HFpEF (n = 19). We performed CMR scans at rest and during a stress test using isometric handgrip exercise (HG). Assessing the MyoHealth score at rest revealed preserved regional strain in 85 ± 9% of LV segments in controls, 73 ± 11% in at Risk subjects and 73 ± 8% in HFpEF patients. During stress the MyoHealth score was 84 ± 7% in controls, 83 ± 7 in at risk subjects and 74 ± 11 in HFpEF patients. Conclusion: In summary, we show for the first time that asymptomatic subjects with increased CV risk present with HFpEF like impaired myocardial deformation at rest, while they show results like controls under HG stress. The potential of preventive treatment in this group of patients merits further investigation in future. Clinical trial registration: [https://drks.de/search/de/trial/DRKS00015615], identifier [DRKS00015615].

Effect of acute sympathetic activation on leg vasodilation before and after endurance exercise.

Vascular conductance (VC) regulation involves a continuous balance between metabolic vasodilation and sympathetic vasoconstriction. Endurance exercise challenges the sympathetic control on VC due to attenuated sympathetic receptor responsiveness and persistence of muscle vasodilation, especially in endurance athletes, predisposing them to blood pressure control dysfunctions. This study assessed whether acute handgrip-mediated sympathetic activation (SYMP) restrains sudden leg vasodilation before and after a half-marathon. Prior to, and within the 20 min following the race, 11 well-trained runners underwent two single passive leg movement (SPLM) tests to suddenly induce leg vasodilation, one without and the other during SYMP. Leg blood flow and mean arterial pressure were measured to assess changes in leg VC. Undertaking 60 sec of SYMP reduced the baseline leg VC both before (4.0 ± 1.0 vs. 3.3 ± 0.7 ml/min/mmHg; P=0.01; NO SYMP vs. SYMP, respectively) and after the race (4.6 ± 0.8 vs. 3.9 ± 0.8 ml/min/mmHg; P=0.01). However, SYMP did not reduce leg peak vasodilation immediately after the SPLM either before (11.5 ± 4.0 vs. 12.2 ± 3.8 ml/min/mmHg; P=0.35) or after the race (7.2 ± 2.0 vs. 7.3 ± 2.6 ml/min/mmHg; P=0.96). Furthermore, SYMP did not blunt the mean leg vasodilation over the 60 sec after the SPLM before (5.1 ± 1.7 vs. 5.9 ± 2.5 ml/min/mmHg; P=0.14) or after the race (4.8 ± 1.3 vs. 4.2 ± 1.5 ml/min/mmHg; P=0.26). This data suggest that the release of local vasoactive agents effectively opposes any preceding handgrip-mediated augmented vasoconstriction in endurance athletes before and after a half-marathon. Handgrip-mediated SYMP might improve normal vasoconstriction while athletes are still, but not necessarily while they move, as movements can induce a release of vasoactive molecules.

Comparison of haemodynamic response to muscle reflex in heart failure with reduced vs. preserved ejection fraction.

AIMS: Isometric handgrip (IHG) training reduces the blood pressure in patients with hypertension. It is unclear how IHG exercise affects the haemodynamics and cardiovascular function through the muscle reflex in patients with heart failure (HF) with reduced (HFrEF) and preserved ejection fraction (HFpEF). METHODS AND RESULTS: Twenty patients (HFrEF: n = 10, HFpEF: n = 10) underwent left ventricular (LV) pressure-volume assessments using a conductance catheter and microtip manometer to evaluate haemodynamics, LV and arterial function, and LV-arterial coupling during 3 min of IHG at 30% of maximal voluntary contraction (MVC), followed by 3 min of post-exercise circulatory arrest (PECA). Three minutes of IHG exercise produced significant and modest increases in the heart rate (HR) and LV end-systolic pressure (LVESP), respectively, in both HFpEF and HFrEF groups. In HFrEF, the increase in LVESP was caused by the variable increase in effective arterial elastance (Ea), which was counterbalanced by the increase in LV end-systolic elastance (Ees), resulting in a maintained Ees/Ea. In HFpEF, the increase in LVESP was not accompanied by changes in Ea, Ees, Ees/Ea, or LV end-diastolic pressure. LVESP during PECA was not maintained in HFpEF, suggesting smaller metabo-reflex activity in HFpEF. CONCLUSIONS: The IHG exercise used in this study may increase the LVESP and LVEDP without detrimental effects on cardiac function or ventricular-arterial coupling, especially in HFpEF patients. The effects of IHG exercise on haemodynamics and ventricular-arterial coupling may be affected by the patient background and the type and intensity of the exercise.

Aerobic exercise, but not isometric handgrip exercise, improves endothelial function and arterial stiffness in patients with myocardial infarction undergoing coronary intervention: a randomized pilot study.

BACKGROUND: Aerobic exercise improves endothelial function and arterial stiffness after myocardial infarction (MI), but the effects of isometric exercise on cardiovascular parameters are still uncertain. We aimed to assess the effects of one session of aerobic or isometric exercise on flow-mediated dilation (FMD) and pulse wave velocity (PWV) in post-MI volunteers undergoing percutaneous coronary intervention (PCI). METHODS: Twenty post-MI patients undergoing PCI were randomized to aerobic (AE, n = 10) or isometric (IE, n = 10) exercise groups. We evaluated cardiac structure and function (echocardiographic); carotid plaque presence (ultrasound). FMD and PWV were measured 10 min before and 10 min after the intervention: a single session of moderate-intensity AE (30 min; ratings 12-14 on Borg's scale or 50-60% HRreserve) or handgrip IE (four two-minute bilateral contractions; 30% maximal voluntary contraction; 1-min rest). Generalized estimating equations (Bonferroni post-hoc) was used to assess differences (p ≤ 0.050). RESULTS: FMD improved only in the AE group (Δ = 4.9%; p = 0.034), with no difference between groups after exercise. Even after adjustment (for baseline brachial artery diameter) the effectiveness of AE remained (p = 0.025) with no change in the IE group. PWV was slightly reduced from baseline in the AE group (Δ = 0.61 m/s; p = 0.044), and no difference when compared to the IE group. Peripheral vascular resistance decreased in AE versus IE (p = 0.050) and from baseline (p = 0.014). CONCLUSIONS: Vascular measurements (FMD and PWV) improved after a single session of AE. There are apparently no benefits following a session of IE. TRIAL REGISTRATION: http://www.clinicaltrials.gov and ID number NCT04000893.