George A. RoseRichard G. DaviesIan R. AppaduraiIan M. Williams...
13页
查看更多>>摘要：New Findings What is the topic of this review? The relationships and physiological mechanisms underlying the clinical benefits of cardiorespiratory fitness (CRF) in patients undergoing major intra‐abdominal surgery. What advances does it highlight? Elevated CRF reduces postoperative morbidity/mortality, thus highlighting the importance of CRF as an independent risk factor. The vascular protection afforded by exercise prehabilitation can further improve surgical risk stratification and postoperative outcomes. Abstract Surgery accounts for 7.7% of all deaths globally and the number of procedures is increasing annually. A patient's ‘fitness for surgery’ describes the ability to tolerate a physiological insult, fundamental to risk assessment and care planning. We have evolved as obligate aerobes that rely on oxygen (O2). Systemic O2 consumption can be measured via cardiopulmonary exercise testing (CPET) providing objective metrics of cardiorespiratory fitness (CRF). Impaired CRF is an independent risk factor for mortality and morbidity. The perioperative period is associated with increased O2 demand, which if not met leads to O2 deficit, the magnitude and duration of which dictates organ failure and ultimately death. CRF is by far the greatest modifiable risk factor, and optimal exercise interventions are currently under investigation in patient prehabilitation programmes. However, current practice demonstrates potential for up to 60% of patients, who undergo preoperative CPET, to have their fitness incorrectly stratified. To optimise this work we must improve the detection of CRF and reduce potential for interpretive error that may misinform risk classification and subsequent patient care, better quantify risk by expressing the power of CRF to predict mortality and morbidity compared to traditional cardiovascular risk factors, and improve patient interventions with the capacity to further enhance vascular adaptation. Thus, a better understanding of CRF, used to determine fitness for surgery, will enable both clinicians and exercise physiologists to further refine patient care and management to improve survival.
Ethan PetersonChristopher P. CardozoZachary A. GrahamPhilip Gallagher...
7页
查看更多>>摘要：New Findings What is the central question of this study? Do Notch, Numb and Numb‐like expression change in human skeletal muscle after exercise‐induced muscle damage? What are the main finding and its importance? Notch gene expression trends toward an increase in response to an acute bout of exercise‐induced muscle damage, while Numb and Numb‐like expression does not change. These results suggest that human skeletal muscle response to exercise‐induced muscle damage is dynamic and may differ from Drosophila and rodent models. Furthermore, the timing of muscle biopsies, training status and muscle damage protocols should be considered. Abstract This investigation examined changes in the gene and protein expression of Notch, Numb and Numb‐like (Numbl) in human skeletal muscle after an acute bout of eccentric exercise‐induced muscle damage. Twelve recreationally active male subjects participated in this study. These individuals completed seven sets of 10 repetitions of eccentric leg extension at 120% of one‐repetition max with 2?min of rest period between sets. Four muscle biopsies of the vastus lateralis were collected: before exercise (Pre), and 3?h, 2 days and 5 days post‐muscle damage. Biopsy samples were used to probe Notch, Numb and Numbl utilizing western blot and RT‐qPCR techniques. The results were analysed using a one‐way repeated‐measures ANOVA. Notch1 mRNA expression trended toward a significant increase from Pre to 2?days post‐muscle damage from baseline measures (P?=?0.087), while Numb (P?=?0.804) and Numbl (P?=?0.480) expression was unaltered post‐muscle damage. There were no significant differences in protein expression post‐muscle damage for any of the proteins. These results suggest that exercise‐induced muscle damage, via eccentric exercise, slightly elevates Notch1 mRNA expression.
查看更多>>摘要：New Findings What is the central question of this study? Is the expression of platelet‐derived growth factor (PDGF) and thromboxane A2 (TXA2) elevated in chronic altitude patients, and are they related to thrombosis in chronic mountain sickness? What is the main finding and its importance? The expression of PDGF and TXA2 in both the bone marrow and the peripheral blood of patients with chronic mountain sickness is elevated, and they are considered to be correlated in the mechanism of thrombosis in the chronic mountain sickness. Abstract The purpose of this study was to evaluate the expression of platelet‐derived growth factor (PDGF) and thromboxane A2 (TXA2) along with platelet parameters and coagulation indices in chronic mountain sickness (CMS) patients and healthy individuals on the Qinghai‐Tibet Plateau. The levels of PDGF and TXA2 were examined in 22 CMS patients (age, 52.77 ± 9.92 years, haemoglobin, 219 ± 13 g/l) and 25 healthy individuals (age, 47.80 ± 9.78 years, haemoglobin, 146 ± 18 g/l), and the association between platelet parameters and coagulation indices was investigated. Mean platelet volume and fibrinogen degradation product were higher in the CMS compared to the control group (10.58 ± 0.83 vs. 8.92?± 1.61, 7.50?± 2.15 vs. 4.40?± 2.51), platelet count and plateletcrit were lower in the CMS compared to the control group (0.13 (0.80, 0.16) vs. 0.23 (0.18, 0.24), 109 ± 46 vs. 204 ± 86). The levels of PDGF and TXA2 in the bone marrow and peripheral blood of CMS patients were higher (P?<?0.01) in comparison to the control group. The two factors had no statistically significant relationship with platelet parameters or coagulation indices (P?>?0.159). According to the current findings, platelets in CMS patients were activated, resulting in aberrant coagulation and PDGF and TXA2 expression, which could be due to physiological adjustments to the plateau's high altitude. To summarize, PDGF and TXA2 levels in CMS patients were not correlated with coagulation or platelet parameters, implying that the mechanism behind their increased expression warrants additional investigation.
查看更多>>摘要：New Findings What is the central question of this study? Exercise training increases adropin and nitrite/nitrate (NOx) plasma levels in middle‐aged and older healthy people. We hypothesized that high‐intensity interval training may improve blood pressure and flow‐mediated dilatation through the effects of adropin and NOx in patients of this age with type 2 diabetes. What is the main finding and its importance? High‐intensity interval training may be more effective than moderate‐intensity continuous training in improving endothelial function, blood pressure and flow‐mediated dilatation through its effects on adropin and NOx in patients with type 2 diabetes. Abstract Adropin is a newly identified bioactive protein that is important in energy hemostasis and vascular endothelial function. Lower levels of adropin in patients with type 2 diabetes are related to coronary atherosclerosis, characterized by impaired flow‐mediated dilatation (FMD). The purpose of the present study was to investigate FMD and plasma levels of adropin and nitrite/nitrate (NOx) in patients with type 2 diabetes at baseline and follow‐up after 12?weeks of high‐intensity interval training (HIIT) or moderate‐intensity continuous training (MICT). Sixty‐six persons with type 2 diabetes were divided into HIIT, MICT, and control groups. The HIIT group intervention was 12 intervals (1.5?min) at 85–90% maximal heart rate (HRmax) separated by 2?min at 55–60% HRmax in three sessions per week for 12?weeks. MICT training consisted of 42?min of cycling at 70% HRmax. Before and after the intervention, FMD was recorded with high‐resolution Doppler ultrasound. Plasma levels of adropin and NOx were measured by enzyme‐linked immunosorbent assay. After training FMD was significantly higher in the MICT and HIIT groups compared to the control group (P?<?0.05). Plasma levels of adropin and NOx were higher in both exercise groups, but the increase was greater in the HIIT group (P?<?0.01). Peak oxygen consumption was increased after exercise training in both groups compared to the control group (P?<?0.01). Percentage FMD showed a positive correlation with plasma levels of adropin and NOx (both P?<?0.01), and a negative correlation with diastolic blood pressure (r?=??0.530, P?=?0.035) and systolic blood pressure (r?=??0.606, P?=?0.013) in the HIIT group. The results indicate that HIIT improved FMD whilst increasing adropin, NOx and peak oxygen consumption. Increased plasma levels of adropin may contribute, in part, to blood pressure reduction by increasing nitric oxide production.
查看更多>>摘要：New Findings What is the central question of this study? Sympathetic vasomotor outflow is reduced during low‐intensity dynamic leg exercise in younger individuals: does ageing influence the sympathoinhibitory effect during low‐intensity leg cycling? What is the main finding and its importance? Muscle sympathetic nerve activity during low‐intensity cycling decreased in older males, as seen in young males. It is possible that cardiopulmonary baroreflex‐mediated inhibition of sympathetic vasomotor outflow during dynamic leg exercise is preserved in healthy older males. Abstract Muscle sympathetic nerve activity (MSNA) is reduced during low‐intensity dynamic leg exercise in young males. It is suggested that this inhibition is mediated by loading of the cardiopulmonary baroreceptors. The purpose of this study was to clarify the impact of age on MSNA during dynamic leg exercise. Nine younger males (YM, mean?±?SD, 20?±?1?years) and nine older males (OM, 72?±?3?years) completed the study. The subjects performed two 4‐min cycling exercises at 10% of their heart rate reserve using a cycle ergometer in a semirecumbent position (MSNA and estimated central venous pressure (eCVP) trials). MSNA was recorded via microneurography of the left radial nerve. The CVP was estimated based on peripheral venous pressure, which was monitored using a cannula in the right large antecubital vein. The magnitude of the increase in mean arterial blood pressure during leg cycling was larger in OM (+9.3?±?5.5?mmHg) compared with YM (+2.8?±?4.7?mmHg). MSNA burst frequency was decreased during cycling in both YM (–8.1?±?3.8?bursts/min) and OM (–10.6?±?3.3?bursts/min), but no significant difference was found between the two groups. The eCVP increased during exercise in both groups, and there was no difference in the changes in eCVP between YM (+1.1?±?0.4?mmHg) and OM (+1.2?±?0.7?mmHg). These data indicate that inhibition of sympathetic vasomotor outflow during low‐intensity cycling appears in OM as seen in YM. It is possible that the muscle pump‐induced loading of the cardiopulmonary baroreflex is preserved during cycling in healthy older males.
Marcel RuzickaTatsuro AmanoGlen P. KennyNaoto Fujii...
10页
查看更多>>摘要：New Findings What is the central question of this study? Does acute intradermal administration of the antioxidant ascorbate augment local forearm cutaneous vasodilatation and sweating via nitric oxide synthase (NOS)‐dependent mechanisms during exercise‐heat stress in older adults with uncomplicated controlled hypertension? What is the main finding and its importance? Relative to the control site, ascorbate had no effect on forearm cutaneous vascular conductance (CVC) and sweat rate, although CVC was reduced with NOS inhibition in older adults with hypertension. Acute local administration of ascorbate to forearm skin does not modulate heat loss responses during exercise‐heat stress in older adults with hypertension. Abstract Nitric oxide synthase (NOS) contributes to the heat loss responses of cutaneous vasodilatation and sweating during exercise. However, the contribution of NOS may be attenuated in individuals with uncomplicated, controlled hypertension due to elevated oxidative stress, which can reduce NO bioavailability. We evaluated the hypothesis that the acute local intradermal administration of the antioxidant ascorbate would enhance cutaneous vasodilatation and sweating via NOS‐dependent mechanisms during an exercise‐heat stress in adults with hypertension. Habitually active adults who were normotensive (n?=?14, 7 females, 62?±?4?years) or had uncomplicated, controlled hypertension (n?=?13, 6 females, 62?±?5?years) performed 30?min of moderate‐intensity (50% of their pre‐determined peak oxygen uptake) semi‐recumbent cycling in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and sweat rate were assessed at four forearm skin sites continuously perfused with (1) lactated Ringer solution (Control), (2) 10?mM antioxidant ascorbate, (3) 10?mM?NG‐nitro‐l‐arginine methyl ester (l‐NAME), a non‐selective NOS inhibitor, or (4) a combination of ascorbate and l‐NAME. Relative to Control, no effect of ascorbate was observed on CVC or sweating in either group (P?=?0.619). However, l‐NAME reduced CVC relative to Control in both groups (P?≤?0.038). No effect of any treatment on sweating was observed (P?≥?0.306). Thus, acute local administration of ascorbate to forearm skin does not enhance the activation of heat loss responses of cutaneous vasodilatation and sweating in older adults, and those with hypertension during an exercise‐heat stress.
Naoto FujiiTatsuro AmanoGlen P. KennyToby Mündel...
10页
查看更多>>摘要：New Findings What is the central question of this study? Do transmembrane member 16A (TMEM16A) blockers modulate the activation of heat loss responses of sweating and cutaneous vasodilatation? What are the main finding and its importance? Relative to the vehicle control site, TMEM16A blockers T16Ainh‐A01 and benzbromarone had no effect on sweat rate or cutaneous vascular conductance during whole‐body heating inducing a 1.1?±?0.1°C increase in core temperature above baseline resting levels. These results suggest that TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation during whole‐body heat stress. Abstract Animal and in vitro studies suggest that transmembrane member 16A (TMEM16A), a Ca2+‐activated Cl? channel, contributes to regulating eccrine sweating. However, direct evidence supporting this possibility in humans is lacking. We assessed the hypothesis that TMEM16A blockers attenuate sweating during whole‐body heating in humans. Additionally, we assessed the associated changes in the heat loss response of cutaneous vasodilatation to determine if a functional role of TMEM16A may exist. Twelve young (24?±?2?years) adults (six females) underwent whole‐body heating using a water‐perfused suit to raise core temperature 1.1?±?0.1°C above baseline. Sweat rate and cutaneous vascular conductance (normalized to maximal conductance via administration of sodium nitroprusside) were evaluated continuously at four forearm skin sites treated continuously by intradermal microdialysis with (1) lactated Ringer's solution (control), (2) 5% dimethyl sulfoxide (DMSO) serving as a vehicle control, or (3) TMEM16A blockers 1?mM T16Ainh‐A01 or 2?mM benzbromarone dissolved in 5% DMSO solution. All drugs were administered continuously via intradermal microdialysis. Whole‐body heating increased core temperature progressively and this was paralleled by an increase in sweat rate and cutaneous vascular conductance at all skin sites. However, sweat rate (all P?>?0.318) and cutaneous vascular conductance (all P?≥?0.073) did not differ between the vehicle control site relative to the TMEM16A blocker‐treated sites. Collectively, our findings indicate that TMEM16A blockers T16Ainh‐A01 and benzbromarone do not modulate the regulation of sweating and cutaneous vasodilatation during whole‐body heating in young adults in vivo.
Kevin L. WebbAhmed N. ElshaerPaolo B. DominelliJonathon W. Senefeld...
10页
查看更多>>摘要：New Findings What is the central question of this study? Do humans with high‐affinity haemoglobin (HAH) demonstrate attenuated skeletal muscle deoxygenation during normoxic and hypoxic exercise? What is the main finding and its importance? Examination of near‐infrared spectroscopy‐derived muscle oxygenation profiles suggests that fractional oxygen extraction is blunted during hypoxic exercise in humans with HAH compared with control subjects. However, muscle tissue oxygen saturation levels were higher in humans with HAH during exercise in normoxia compared with control subjects. These alterations in fractional oxygen extraction in humans with HAH might influence blood flow regulation and exercise capacity during hypoxia. Abstract Recently, researchers in our laboratory have shown that humans with genetic mutations resulting in high‐affinity haemoglobin (HAH) demonstrate better maintained aerobic capacity and peak power output during hypoxic exercise versus normoxic exercise in comparison to humans with normal‐affinity haemoglobin. However, the influence of HAH on tissue oxygenation within exercising muscle during normoxia and hypoxia is unknown. Therefore, we examined near‐infrared spectroscopy‐derived oxygenation profiles of the vastus lateralis during graded cycling exercise in normoxia and hypoxia among humans with HAH (n?=?5) and control subjects with normal‐affinity haemoglobin (n?=?12). The HAH group elicited a blunted increase of deoxygenated haemoglobin?+?myoglobin during hypoxic exercise compared with the control group (P = 0.03), suggesting reduced fractional oxygen extraction in the HAH group. In addition, the HAH group maintained a higher level of muscle tissue oxygen saturation during normoxic exercise (HAH, 75 ± 4% vs. controls, 65 ± 3%, P = 0.049) and there were no differences between groups in muscle tissue oxygen saturation during hypoxic exercise (HAH, 68 ± 3% vs. controls, 68 ± 2%, P = 0.943). Overall, our results suggest that humans with HAH might demonstrate divergent patterns of fractional oxygen extraction during hypoxic exercise and elevated muscle tissue oxygenation during normoxic exercise compared with control subjects.
查看更多>>摘要：New Findings What is the central question of this study? Can the triangular appearance of ventricular action potential, indicating proarrhythmic profile of antiarrhythmic agent, be approximated by specific changes on an electrocardiogram (ECG)? What are the main finding and its importance? The triangulation of the ventricular action potential seen when antiarrhythmic drugs induce a greater lengthening of the late repolarization compared to the initial repolarization in epicardium is closely approximated by a greater prolongation of the T wave upslope relative to the interval between the J point and the start of the T wave (the JTstart interval) on the ECG. These findings may improve the power of ECG assessments in predicting the drug‐induced arrhythmia resulting from slowed phase 3 repolarization. Abstract Antiarrhythmic drugs prescribed to treat atrial fibrillation can occasionally precipitate ventricular tachyarrhythmia through a prominent slowing of the phase 3 repolarization. The latter results in the triangular shape of ventricular action potential, indicating high arrhythmic risk. However, clinically, the utility of triangulation assessments for predicting arrhythmia is limited owing to the invasive nature of the ventricular action potential recordings. This study examined whether the triangulation effect can be detected indirectly from electrocardiogram (ECG) analysis. Epicardial monophasic action potentials and the ECG were simultaneously recorded in perfused guinea‐pig hearts. With antiarrhythmics (dofetilide, quinidine, procainamide and flecainide), a prolongation of the initial repolarization seen in the action potential recordings was closely approximated by lengthening of the interval between the J point and the start of the T wave (the JTstart interval) on the ECG, whereas a prolongation of the late repolarization was paralleled by widening of the T wave upslope. Dofetilide, quinidine and procainamide induced a prominent slowing of the phase 3 repolarization in epicardium, leading to triangulation of the action potential. These effects were accompanied by a greater prolongation of the T wave upslope compared to the JTstart interval. Flecainide elicited a proportional prolongation of the initial and the late ventricular repolarization, and therefore failed to induce triangulation, based on analysis of both epicardial action potential and ECG profiles. Collectively, these findings suggest that the ratio between the durations of the T wave upslope and the JTstart interval may represent the ECG metric of the ventricular action potential triangulation induced by antiarrhythmic drugs.
查看更多>>摘要：New Findings What is the central question of this study? Does the advanced glycation end products (AGEs)–receptor for advanced glycation end products (RAGE) axis mediate myocardial fibrosis in heart failure? What is the main finding and its importance? The AGEs–RAGE axis is involved in the pathogenesis of myocardial fibrosis through activation of cardiac fibroblasts induced by autophagy in heart failure. By suppression of cardiac fibroblast activation, inhibition of the AGEs–RAGE axis attenuates cardiac dysfunction and myocardial fibrosis in mice with transverse aortic constriction. Abstract Heart failure is the end stage of cardiovascular disease and is a critical medical condition that poses an important therapeutic challenge for physicians owing to its high morbidity and mortality. Myocardial fibrosis is part of the remodelling process that occurs in heart failure. Many studies have shown that advanced glycation end products (AGEs) and receptor for advanced glycation end products (RAGE) are implicated in fibrosis and autophagy, but the mechanism remains unclear. In this study, we elucidated the mechanism by which the AGEs–RAGE axis mediates activation of cardiac fibroblasts (CFs) in heart failure. We used C57BL/6J wild‐type (WT) mice to establish a model of heart failure by transverse aortic constriction (TAC). After 6?weeks of treatment, relevant indicators were detected. In mice subjected to TAC, AGEs were upregulated compared with sham‐operated mice. Inhibition of RAGE resulted in functional cardiac protection, with reduced hypertrophy and fibrosis in mice after TAC. Of note, autophagy mediated the activation of CFs that transformed to myofibroblasts and contributed to fibrosis. In vitro, CFs were obtained from neonatal Sprague–Dawley rats and treated with AGEs, bovine serum albumin and short hairpin RNA (shRNA) for RAGE, in order to verify the results obtained in vivo. These results suggest that the AGEs–RAGE axis is involved in the pathogenesis of myocardial fibrosis in heart failure through CF activation induced by autophagy. Inhibition of the AGEs–RAGE axis attenuates cardiac dysfunction and myocardial fibrosis in mice with TAC by suppressing CF activation.
NSTL
Wiley