Acute physiological responses to high-intensity interval exercise in patients with coronary artery disease.

PURPOSE: Time spent closer to maximal effort during exercise is a potent stimulus for cardiorespiratory adaptations. The primary purpose was to determine which high-intensity interval exercise (HIIE) protocol provided the greatest physiological stimulus by comparing time spent ≥ 90% peak oxygen consumption (V̇O2peak) and heart rate reserve (HRR) in patients with coronary artery disease (CAD) in response to 3 HIIE protocols and the exercise standard of care, moderate-intensity continuous exercise (MICE). A secondary purpose was to assess protocol preference. METHODS: Fifteen patients with CAD (6 females, 67 ± 6 years) underwent measurements of V̇O2 and heart rate during MICE and three HIIE protocols all performed on a treadmill. The HIIE protocols included one with long intervals (4 × 4-min), short intervals (10 × 1-min), and an adapted version of the 4 × 4 [Toronto Rehabilitation Institute Protocol, (TRIP)]. Time spent ≥ 90% V̇O2peak and HRR were compared. RESULTS: Time spent ≥ 90% V̇O2peak was higher during 4 × 4 (6.3 ± 8.4 min) vs. MICE (1.7 ± 3.9 min; P = 0.001), while time spent ≥ 90% HRR was higher during 4 × 4 (6.0 ± 5.3 min) vs. MICE (0.1 ± 0.2 min; P < 0.001) and 10 × 1 (0.7 ± 0.8 min; P = 0.016). TRIP had similar responses as 10 × 1 and MICE. The 10 × 1 was the most preferred protocol and the 4 × 4 was the least preferred protocol. CONCLUSION: Longer intervals (4 × 4) provided the greatest physiological stimulus compared to the exercise standard of care and shorter intervals. However, this protocol was least preferred which may impact exercise adherence. Although the physiological stimulus is important to maximize training adaptations, exercise preferences and attitudes should be considered.

Differential negative effects of acute exhaustive swim exercise on the right ventricle are associated with disproportionate hemodynamic loading.

Acute exhaustive endurance exercise can differentially impact the right ventricle (RV) versus the left ventricle (LV). However, the hemodynamic basis for these differences and its impact on postexercise recovery remain unclear. Therefore, we assessed cardiac structure and function along with hemodynamic properties of mice subjected to single bouts (216 ± 8 min) of exhaustive swimming (ES). One-hour after ES, LVs displayed mild diastolic impairment compared with that in sedentary (SED) mice. Following dobutamine administration to assess functional reserve, diastolic and systolic function were slightly impaired. Twenty-four hours after ES, LV function was largely indistinguishable from that in SED. By contrast, 1-h post swim, RVs showed pronounced impairment of diastolic and systolic function with and without dobutamine, which persisted 24 h later. The degree of RV impairment correlated with the time-to-exhaustion. To identify hemodynamic factors mediating chamber-specific responses to ES, LV pressure was recorded during swimming. Swimming initiated immediate increases in heart rates (HRs), systolic pressure, dP/dtmax and -dP/dtmin, which remained stable for ∼45 min. LV end-diastolic pressures (LVEDP) increased to ≥45 mmHg during the first 10 min and subsequently declined. After 45 min, HR and -dP/dtmin declined, which correlated with gradual elevations in LVEDP (to ∼45 mmHg) as mice approached exhaustion. All parameters rapidly normalized postexercise. Consistent with human studies, our findings demonstrate a disproportionate negative impact of acute exhaustive exercise on RVs that persisted for at least 24 h. We speculate that the differential effects of exhaustive exercise on the ventricles arise from a ∼2-fold greater hemodynamic load in the RV than in LV originating from profound elevations in LVEDPs as mice approach exhaustion.NEW & NOTEWORTHY Acute exhaustive exercise differentially impacts the right ventricle (RV) versus left ventricle (LV), yet the underlying hemodynamic basis remains unclear. Using pressure-volume analyses and pressure-telemetry implantation in mice, we confirmed a marked disproportionate and persistent negative impact of exhaustive exercise on the RV. These differences in responses of the ventricles to exhaustive exercise are of clinical relevance, reflecting ∼2-fold greater hemodynamic RV loads versus LVs arising from massive (∼45 mmHg) increases in LV end-diastolic pressures at exhaustion.

Exercise in hypertrophic cardiomyopathy: restrict or rethink.

The detailed physiological consequences of aerobic training, in patients with hypertrophic cardiomyopathy (HCM), are not well understood. In athletes and nonathletes with HCM, there are two hypothetical concerns with respect to exercise: exercise-related worsening of the phenotype (e.g., promoting hypertrophy and fibrosis) and/or triggering of arrhythmia. The former concern is unproven and animal studies suggest an opposite effect, where exercise has been shown to be protective. The main reason for exercise restriction in HCM is fear of exercise-induced arrhythmia. Although the safety of sports in HCM has been reviewed, even more recent data suggest a substantially lower risk for sudden cardiac death (SCD) in HCM than previously thought, and there is an ongoing debate about restrictions of exercise imposed on individuals with HCM. This review outlines the pathophysiology of HCM, the impact of acute and chronic exercise (and variations of exercise intensity, modality, and athletic phenotype) in HCM including changes in autonomic function, blood pressure, cardiac dimensions and function, and cardiac output, and the underlying mechanisms that may trigger exercise-induced lethal arrhythmias. It provides a critical evaluation of the evidence regarding risk of SCD in athletes and the potential benefits of targeted exercise prescription in adults with HCM. Finally, it provides considerations for personalized recommendations for sports participation based on the available data.

Cardiac remodeling in middle-aged endurance athletes: relation between signal-averaged electrocardiogram and LV mass.

The relationship between structural and electrical remodeling in the heart, particularly after long-standing endurance training, remains unclear. Signal-averaged electrocardiogram (SAECG) may provide a more sensitive method to evaluate cardiac remodeling than a 12-lead electrocardiogram (ECG). Accurate measures of electrical function (SAECG filtered QRS duration (fQRSd) and late potentials (LP) and left-ventricular (LV) mass (cardiac magnetic resonance, CMR) can allow an assessment of structural remodeling and QRS prolongation. Endurance athletes (45-65 yr old, >10 yr of endurance sport), screened to exclude cardiac disease, had standardized 12-lead ECG, SAECG, resting echocardiogram (ECHO), and CMR performed. SAECG fQRSd was correlated with QRS duration on the 12-lead ECG, and ECHO and CMR-derived LV mass. Participants (n = 82, 67% male, mean age: 54 ± 6 yr, mean V̇o2max: 50 ± 7 mL/kg/min) had a CMR-derived LV mass of 118 ± 28 g/m2 and a fQRSd of 112 ± 8 ms (46% had abnormal fQRSd (>114 ms), and 51% met clinical threshold for abnormal SAECG). fQRSd was positively correlated with the 12-lead ECG QRS duration (r = 0.83), ECHO-derived LV mass (r = 0.60), CMR-derived LV mass (r = 0.58) and LV end-diastolic volume (r = 0.63, P < 0.001 for all). fQRSd had higher correlations with ECHO and CMR-derived LV mass than 12-lead ECG (P < 0.0008 and P < 0.0005, respectively). In conclusion, in a healthy cohort of middle-aged endurance athletes, the SAECG is often abnormal by conventional criteria, and is correlated with structural remodeling, but CMR evaluation does not indicate pathologic structural remodeling. SAECG fQRSd is superior to the 12-lead ECG for the electrocardiographic evaluation of LV mass.NEW & NOTEWORTHY Study findings indicate that a positive correlation exists between electrical (SAECG fQRSd) and structural indices (LV mass) in middle-aged endurance athletes with normal physiological LV adaptation, in the absence of known cardiac pathology. SAECG fQRSd may also provide an alternative, superior method for identifying increased LV mass compared to other 12-lead ECG criteria.

Synthesis of Bench-Stable N-Quaternized Ketene N,O-Acetals and Preliminary Evaluation as Reagents in Organic Synthesis.

N-Quaternized ketene N,O-acetals are typically an unstable, transient class of compounds most commonly observed as reactive intermediates. In this report, we describe a general synthetic approach to a variety of bench-stable N-quaternized ketene N,O-acetals via treatment of pyridine or aniline bases with acetylenic ethers and an appropriate Brønsted or Lewis acid (triflic acid, triflimide, or scandium(III) triflate). The resulting pyridinium and anilinium salts can be used as reagents or synthetic intermediates in multiple reaction types. For example, N-(1-ethoxyvinyl)pyridinium or anilinium salts can thermally release highly reactive O-ethyl ketenium ions for use in acid catalyst-free electrophilic aromatic substitutions. N-(1-Ethoxyvinyl)-2-halopyridinium salts can be employed in peptide couplings as a derivative of Mukaiyama reagents or react with amines in nucleophilic aromatic substitutions under mild conditions. These preliminary reactions illustrate the broad potential of these currently understudied compounds in organic synthesis.

Isoflavone levels, nodulation and gene expression profiles of a CRISPR/Cas9 deletion mutant in the isoflavone synthase gene of red clover.

KEY MESSAGE: Isoflavones are not involved in rhizobial signaling in red clover, but likely play a role in defense in the rhizosphere. Red clover (Trifolium pratense) is a high-quality forage legume, well suited for grazing and hay production in the temperate regions of the world. Like many legumes, red clover produces a number of phenylpropanoid compounds including anthocyanidins, flavan-3-ols, flavanols, flavanones, flavones, and isoflavones. The study of isoflavone biosynthesis and accumulation in legumes has come into the forefront of biomedical and agricultural research due to potential for medicinal, antimicrobial, and environmental implications. CRISPR/Cas9 was used to knock out the function of a key enzyme in the biosynthesis of isoflavones, isoflavone synthase (IFS1). A hemizygous plant carrying a 9-bp deletion in the IFS1 gene was recovered and was intercrossed to obtain homozygous mutant plants. Levels of the isoflavones formononetin, biochanin A and genistein were significantly reduced in the mutant plants. Wild-type and mutant plants were inoculated with rhizobia to test the effect of the mutation on nodulation, but no significant differences were observed, suggesting that these isoflavones do not play important roles in nodulation. Gene expression profiling revealed an increase in expression of the upstream genes producing the precursors for IFS1, namely, phenylalanine ammonium lyase and chalcone synthase, but there were no significant differences in IFS1 gene expression or in the downstream genes in the production of specific isoflavones. Higher expression in genes involved in ethylene response was observed in the mutant plants. This response is normally associated with biotic stress, suggesting that the plants may have been responding to cues in the surrounding rhizosphere due to lower levels of isoflavones.

Structural Basis for GTP versus ATP Selectivity in the NMP Kinase AK3.

ATP and GTP are exceptionally important molecules in biology with multiple, and often discrete, functions. Therefore, enzymes that bind to either of them must develop robust mechanisms to selectively utilize one or the other. Here, this specific problem is addressed by molecular studies of the human NMP kinase AK3, which uses GTP to phosphorylate AMP. AK3 plays an important role in the citric acid cycle, where it is responsible for GTP/GDP recycling. By combining a structural biology approach with functional experiments, we present a comprehensive structural and mechanistic understanding of the enzyme. We discovered that AK3 functions by recruitment of GTP to the active site, while ATP is rejected and nonproductively bound to the AMP binding site. Consequently, ATP acts as an inhibitor with respect to GTP and AMP. The overall features with specific recognition of the correct substrate and nonproductive binding by the incorrect substrate bear a strong similarity to previous findings for the ATP specific NMP kinase adenylate kinase. Taken together, we are now able to provide the fundamental principles for GTP and ATP selectivity in the large NMP kinase family. As a side-result originating from nonlinearity of chemical shifts in GTP and ATP titrations, we find that protein surfaces offer a general and weak binding affinity for both GTP and ATP. These nonspecific interactions likely act to lower the available intracellular GTP and ATP concentrations and may have driven evolution of the Michaelis constants of NMP kinases accordingly.

Indexes of aortic wave reflection are not augmented in estrogen-deficient physically active premenopausal women.

BACKGROUND: Hypoestrogenemia due to menopause is associated with increased cardiovascular disease risk, in part due to elevated indexes of aortic wave reflection (AWRI) and central (aortic) blood pressure. We sought to investigate whether AWRI and central blood pressure are also augmented in hypoestrogenic exercise-trained premenopausal women with functional hypothalamic amenorrhea (ExFHA). METHODS: In age- (pooled mean ± SEM, 24 ± 1 years), BMI- (21 ± 1 kg/m2 ), and cardiorespiratory fitness-matched (45 ± 2 ml/kg/min) eumenorrheic ovulatory (ExOv; n = 11) and ExFHA women (n = 10), we assessed aortic blood pressure and waveform characteristics (augmentation index and wave reflection amplitude) obtained from radial pressure waves (applanation tonometry). Doppler ultrasound determined cardiac output (CO) and total peripheral resistance (TPR). Measures were recorded before and 1 hour after 45 minutes of moderate intensity exercise to determine the influence of exercise-induced increases in nitric oxide. RESULTS: Pre-exercise, AIx75, central systolic BP (SBPc), and CO were lower (P < .05) and TPR higher (P < .05) in ExFHA. Post-exercise, AIx75 was unchanged (P > .05) in ExFHA but was lowered (P < .05) in ExOv. Both groups demonstrated increased CO, and lowered SBPc and TPR, yet TPR remained higher (P < .05), and CO and SBPc lower (P < .05) in ExFHA. CONCLUSIONS: Despite hypoestrogenemia, functional compliance of the central arteries and central BP is not augmented, yet TPR is higher, in ExFHA versus ExOv. An acute bout of dynamic exercise did not alter AIx75 in ExFHA, suggesting blunted vascular responsiveness to exercise-induced increases in nitric oxide, possibly due to augmented vascular tone. These findings have relevance in understanding the vascular consequences of hypoestrogenemia during the premenopausal years.

Pulmonary hemodynamic and right ventricular responses to brief and prolonged exercise in middle-aged endurance athletes.

Right ventricular (RV) function is closely coupled to pulmonary arterial (PA) hemodynamics and is believed to decline with prolonged exercise. A linear pressure-flow relationship is thought to exist between PA pressures and increasing exercise intensity in athletes, yet a paucity of directly measured pulmonary hemodynamic data exists supporting this contention. We sought to describe the PA pressure, PA wedge pressure (PAWP), and RV functional responses to brief and prolonged exercise in endurance-trained athletes. Twenty-one healthy athletes (54 ± 5 yr) underwent right heart catheterization to assess pulmonary hemodynamics during graded, submaximal exercise. Measurements were made at rest and during three stages of steady-state, semiupright cycle ergometry at heart rates of 100 beats/min (EX1), 130 beats/min (EX2), and 150 beats/min (EX3). Five athletes completed an additional 34 min at 130 beats/min for a total exercise time of 60 min [prolonged exercise (PLG)]. PA pressures and PAWP increased significantly at EX1 without a further rise at EX2, EX3, or PLG. PAWP adjusted for absolute work rate demonstrated a significant decline as exercise intensity increased from EX1 to EX2. The resistance compliance time constant decreased at EX1 without further changes at EX2, EX3, and prolonged exercise. RV function did not decline during PLG. After an initial rise in PA pressure and PAWP during early, nonsteady-state exercise, values remained constant despite increases in exercise intensity and duration. These data indicate that in healthy, middle-aged endurance-trained athletes, the PA and pulmonary venous/left atrial compartments rapidly accommodate high conduit flows produced during intensive and prolonged exercise while maintaining RV function. NEW & NOTEWORTHY The right ventricular (RV)-pulmonary arterial (PA) circulatory unit has not been well studied during prolonged exercise, and this study provides an ecological approach that reflects a typical bout of endurance training integrating a transition from rest to exercise with successive increases in intensity, progressing to steady-state, sustained exercise. We demonstrated a remarkably constant response of the PA and PA wedge pressure during incremental, steady-state exercise and that no changes occur in pulmonary pressures throughout prolonged exercise, concomitant to a preservation of RV performance.

The relationship of pulmonary vascular resistance and compliance to pulmonary artery wedge pressure during submaximal exercise in healthy older adults.

KEY POINTS: A consistent inverse hyperbolic relationship has been observed between pulmonary vascular resistance and compliance, although changes in pulmonary artery wedge pressure (PAWP) may modify this relationship. This relationship predicts that pulmonary artery systolic, diastolic and mean pressure maintain a consistent relationship relative to the PAWP. We show that, in healthy exercising human adults, both pulmonary vascular resistance and compliance decrease in relation to exercise-associated increases in PAWP. Pulmonary artery systolic, diastolic and mean pressures maintain a consistent relationship with one another, increasing linearly with increasing PAWP. Increases in PAWP in the setting of exercise are directly related to a decrease in pulmonary vascular compliance, despite small decreases in pulmonary vascular resistance, thereby increasing the pulsatile afterload to the right ventricle. ABSTRACT: The resistive and pulsatile components of right ventricular afterload (pulmonary vascular resistance, Rp; compliance, Cp) are related by an inverse hyperbolic function, expressed as their product known as RpCp-time. The RpCp-time exhibits a narrow range, although it may be altered by the pulmonary artery wedge pressure (PAWP). Identifying the determinants of RpCp-time should improve our understanding of the physiological behaviour of pulmonary arterial systolic (PASP), diastolic (PADP) and mean (mPAP) pressures in response to perturbations. We examined the effect of exercise in 28 healthy non-athletic adults (55 ± 6 years) who underwent right heart catheterization to assess haemodynamics and calculate Rp and Cp. Measurements were made at rest and during two consecutive 8-10 min stages of cycle ergometry, at targeted heart-rates of 100 beats min(-1) (Light) and 120 beats min(-1) (Moderate). Cardiac output increased progressively during exercise. PASP, PADP, mPAP and PAWP increased for Light exercise, without any further rise for Moderate exercise. RpCp-time decreased for Light exercise (0.39 ± 0.08 to 0.25 ± 0.08, P < 0.001) without any further change for Moderate exercise, and the decrease in RpCp-time was related to changes in PAWP (r(2)  = 0.26, P < 0.001). Changes in PASP (r(2)  = 0.43, P < 0.001), PADP (r(2)  = 0.47, P < 0.001) and mPAP (r(2)  = 0.50, P < 0.001) were linearly correlated with changes in PAWP, although they were not significantly related to changes in cardiac output. In healthy adults, exercise is associated with decreases in Cp and a resultant decline in RpCp-time, indicating increased pulsatile right ventricular afterload. Changes in RpCp-time, PASP, PADP and mPAP were systematically related to increases in PAWP.

Augmented vagal heart rate modulation in active hypoestrogenic pre-menopausal women with functional hypothalamic amenorrhoea.

Compared with eumenorrhoeic women, exercise-trained women with functional hypothalamic amenorrhoea (ExFHA) exhibit low heart rates (HRs) and absent reflex renin-angiotensin-system activation and augmentation of their muscle sympathetic nerve response to orthostatic stress. To test the hypothesis that their autonomic HR modulation is altered concurrently, three age-matched (pooled mean, 24 ± 1 years; mean ± S.E.M.) groups of women were studied: active with either FHA (ExFHA; n=11) or eumenorrhoeic cycles (ExOv; n=17) and sedentary with eumenorrhoeic cycles (SedOv; n=17). Blood pressure (BP), HR and HR variability (HRV) in the frequency domain were determined during both supine rest and graded lower body negative pressure (LBNP; -10, -20 and -40 mmHg). Very low (VLF), low (LF) and high (HF) frequency power spectra (ms(2)) were determined and, owing to skewness, log10-transformed. LF/HF ratio and total power (VLF + LF + HF) were calculated. At baseline, HR and systolic BP (SBP) were lower (P<0.05) and HF and total power were higher (P<0.05) in ExFHA than in eumenorrhoeic women. In all groups, LBNP decreased (P<0.05) SBP, HF and total power and increased (P<0.05) HR and LF/HF ratio. However, HF and total power remained higher (P<0.05) and HR, SBP and LF/HF ratio remained lower (P<0.05) in ExFHA than in eumenorrhoeic women, in whom measures did not differ (P>0.05). At each stage, HR correlated inversely (P<0.05) with HF. In conclusion, ExFHA women demonstrate augmented vagal yet unchanged sympathetic HR modulation, both at rest and during orthostatic stress. Although the role of oestrogen deficiency is unclear, these findings are in contrast with studies reporting decreased HRV in hypoestrogenic post-menopausal women.

Short-term high-intensity interval and continuous moderate-intensity training improve maximal aerobic power and diastolic filling during exercise.

PURPOSE: This study examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on cardiac function in young, healthy men. METHODS: Sixteen previously untrained men (mean age of 25.1 ± 4.1 years) were randomly assigned to HIT and CMT (n = 8 each) and assessed before and after six sessions over a 12-day training period. HIT consisted of 8-12 intervals of cycling for 60 s at 95-100% of pre-training maximal aerobic power (VO(2max)), interspersed by 75 s of cycling at 10% VO(2max). CMT involved 90-120 min of cycling at 65% pre-training VO(2max). Left ventricular (LV) function was determined at rest and during submaximal exercise (heart rate ~105 bpm) using two-dimensional and Doppler echocardiography. RESULTS: Training resulted in increased calculated plasma volume (PV) in both groups, accompanied by improved VO(2max) in HIT (HIT: from 39.5 ± 7.1 to 43.9 ± 5.5 mL kg(-1) min(-1); CMT: from 39.9 ± 5.9 to 41.7 ± 5.3 mL kg(-1) min(-1); P < 0.001). Resting LV function was not altered. However, increased exercise stroke volume (P = 0.02) and cardiac output (P = 0.02) were observed, secondary to increases in end-diastolic volume (P < 0.001). Numerous Doppler and speckle tracking indices of diastolic function were similarly enhanced during exercise in both training groups and were related to changes in PV. CONCLUSION: Short-term HIT and CMT elicit rapid improvements in VO2max and LV filling without global changes in cardiac performance at rest.

Left atrial functional changes following short-term exercise training.

BACKGROUND: Exercise-induced adaptations of the human atria remain understudied, particularly early in the training process. We examined the effects of short-term high-intensity interval training (HIT) and continuous moderate-intensity training (CMT) on left atrial (LA) systolic and diastolic function, relative to left ventricular (LV) function in young, healthy men, by speckle tracking echocardiography (STE). METHODS: Fourteen untrained men (mean age = 25 ± 4 years) were randomized to HIT or CMT, and assessed before and after six training sessions over a 12-day period. HIT included 8-12 intervals of cycling for 60 s at 95-100% of maximal aerobic power (VO2MAX), interspersed by 75 s of cycling at 10 % VO2MAX. CMT consisted of 90-120 min of cycling at 65% VO2MAX. RESULTS: VO2MAX increased following HIT and CMT by 11.5 and 5.5%, respectively (p < 0.05). Calculated plasma volume expanded 11 % following HIT and 10% following CMT (p < 0.005). Resting LV volumes and ejection fraction were unaltered following training. Peak atrial longitudinal strain increased following HIT (41.8 ± 5.2%-47.1 ± 3.7%, p < 0.01) and CMT (38.5 ± 4.6%-41.7 ± 6.0%, p < 0.01). Atrial systolic strain rate increased following HIT (1.6 ± 0.2%/s-2.0 ± 0.3%/s, p < 0.01) and CMT (1.6 ± 0.2%/s-1.9 ± 0.2%/s, p < 0.01). CONCLUSIONS: LA function assessed by STE improves rapidly during short-term intensive exercise training.

Left atrial reservoir pressure-volume relations during exercise in healthy older adults.

The left atrium (LA) mediates cardiopulmonary interactions. During ventricular systole, the LA functions as a compliant reservoir that is coupled to the left ventricle (LV) and offloads volume from the pulmonary vasculature. We aimed to describe LA reservoir function using phasic relationships between pulmonary artery wedge pressure (PAWP) and LA volume events. We included healthy adults (7 M/6 F, 56 ± 8 yr) who were studied at rest and during semirecumbent cycle ergometry at a target of 100 beats/min heart rate. Right heart catheterization was performed to record the PAWP and two-dimensional (2-D) echocardiography was used to measure LA and LV volumes. We manually measured A-wave, x-trough, V-wave, and y-trough PAWP beat-by-beat, as well as minimal, maximal, and precontraction biplane LA volumes. Heart rate increased by 40 ± 7 beats/min with exercise; stroke volume and cardiac output also rose. Although all phasic PAWP measurements increased with exercise, the x-V pressure pulse during LA filling doubled from 4 ± 2 to 8 ± 4 mmHg (P = 0.001). LA minimal volume was unchanged but maximal volume increased from 39 ± 9 to 48 ± 9 mL (P < 0.001) with exercise, and so reservoir volume increased from 24 ± 5 to 32 ± 8 mL (P < 0.001). As such, calculated LA compliance decreased from 6.8 ± 3.4 to 4.8 ± 2.6 mL/mmHg (P = 0.029). The product of V-wave PAWP and LA maximal volume, a surrogate for LA wall stress, increased from 486 ± 193 to 953 ± 457 mmHg·mL (P < 0.001). In healthy older adults during submaximal exercise, the PAWP waveform shifts upward and its amplitude widens, LA filling increases, LA compliance decreases modestly, and LA wall stress may augment substantially.NEW & NOTEWORTHY We combined invasive estimates of left atrial pressure with noninvasive left atrial volume measurements made at rest and during exercise in healthy humans. Left atrial pressure and volume both increased with exercise, though the pressure increase was relatively greater, and calculated compliance decreased modestly while estimated peak wall stress nearly doubled. Our results demonstrate left atrial loading during exercise in healthy older adults and provide insight into how the left atrium mediates cardiopulmonary interactions.

The effect of chronic exercise training and acute exercise on power spectral analysis of heart rate variability.

Moderate to vigorous physical activity performed regularly is cardioprotective and reduces all-cause mortality, concomitant with increased resting heart rate variability (HRV). However, there are contradictory reports regarding the effects of chronic and acute exercise on nocturnal HRV in those performing exercise well-beyond physical activity guidelines. Therefore, the purpose of this study was to compare the power spectral analysis components of HRV in middle-aged endurance athletes (EA) and recreationally active individuals (REC) and explore acute exercise effects in EA. A total of 119 EA (52, 49-57 years) and 32 REC (56, 52-60 years) were recruited to complete 24 h Holter monitoring (GE SEER 1000) in the absence of exercise. Fifty one EA (52, 49-57 years) then underwent 24 h Holter monitoring following an intense bout of endurance exercise. Power spectral HRV analysis was completed hourly and averaged to quantify morning (1000-1200 h), evening (1900-2100 h), and nocturnal (0200-0400 h) HRV. EA had greater very low frequency (VLF) and low frequency (LF) (both p < 0.001) compared to REC. LF/high frequency (HF) was greater in EA at 0200-0400 h (p = 0.04). Among all participants, the change in HR and HF from 1000-1200 to 0200-0400 h was negatively correlated (r = -0.47, p < 0.001). Following acute exercise in EA, only nocturnal HRV was assessed. VLF (p < 0.001) and HF (p = 0.008) decreased, while LF/HF increased (p = 0.02). These results suggest that in EA, both long-term and acute exercises increase nocturnal sympathovagal activity through an increase in LF and decrease in HF, respectively. Further work is required to understand the mechanism underlying reduced nocturnal HRV in middle-aged EA and the long-term health implications.

Atrial fibrillation in middle-aged athletes: Impact on left atrial, ventricular and exercise performance.

High volume endurance training may increase the risk of paroxysmal atrial fibrillation (AF) in middle-aged athletes. Limited data are available describing the cardiovascular phenotype of middle-aged endurance athletes, or the impact of AF on atrial function and exercise performance performed in sinus rhythm. The purpose of this study was to characterize LA phasic function at rest and during exercise in athletes with paroxysmal AF, and to determine its impact on exercise performance. Fifteen endurance trained males (EA) (56 ± 5 years) without AF and 14 endurance trained males with paroxysmal AF (EA-AF) (55 ± 8 years) underwent echocardiography during cycle-ergometry at light and moderate intensities. Resting LA maximal volumes were similar between EA and EA-AF (30 ± 4 vs. 29 ± 8 ml/m2, p = 0.50), and there were no differences in atrial electromechanical delay (AEMD). During moderate intensity exercise, EA-AF had reduced LA conduit (30 ± 6 vs. 40 ± 5 ml/m2, p = 0.002) LA booster volumes (17 ± 5 vs. 21 ± 4 ml/m2, p = 0.021), and reduced LV stroke volumes (100 ± 12 vs. 117 ± 16 ml, p = 0.007). These results demonstrate that exercise testing in athletes with AF unmasks evidence of adverse functional cardiac remodelling that may contribute to impaired exercise performance. It is unclear whether these functional alterations are the consequence of AF. Reductions in LA conduit volume, LA booster volume, and LV stroke volume during exercise may be helpful in clinical management and distinguishing pathologic from physiologic remodelling.

Exercise-Dependent Modulation of Immunological Response Pathways in Endurance Athletes With and Without Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a common arrhythmia characterized by uncoordinated atrial electrical activity. Lone AF occurs in the absence of traditional risk factors and is frequently observed in male endurance athletes, who face a 2- to 5-fold higher risk of AF compared with healthy, moderately active males. Our understanding of how endurance exercise contributes to the pathophysiology of lone AF remains limited. This study aimed to characterize the circulating protein fluctuations during high-intensity exercise as well as explore potential biomarkers of exercise-associated AF. METHODS AND RESULTS: A prospective cohort of 12 male endurance cyclists between the ages of 40 and 65 years, 6 of whom had a history of exercise-associated AF, were recruited to participate using a convenience sampling method. The circulating proteome was subsequently analyzed using multiplex immunoassays and aptamer-based proteomics before, during, and after an acute high-intensity endurance exercise bout to assess temporality and identify potential markers of AF. The endurance exercise bout resulted in significant alterations to proteins involved in immune modulation (eg, growth/differentiation factor 15), skeletal muscle metabolism (eg, α-actinin-2), cell death (eg, histones), and inflammation (eg, interleukin-6). Subjects with AF differed from those without, displaying modulation of proteins previously known to have associations with incident AF (eg, C-reactive protein, insulin-like growth factor-1, and angiopoietin-2), and also with proteins having no previous association (eg, tapasin-related protein and α2-Heremans-Schmid glycoprotein). CONCLUSIONS: These findings provide insights into the proteomic response to acute intense exercise, provide mechanistic insights into the pathophysiology behind AF in athletes, and identify targets for future study and validation.

Effects of moderate-intensity aerobic cycling and swim exercise on post-exertional blood pressure in healthy young untrained and triathlon-trained men and women.

Aerobic exercises such as running, walking and cycling are known to elicit a PEH (post-exercise hypotensive) response in both trained and UT (untrained) subjects. However, it is not known whether swim exercise produces a similar effect in normotensive individuals. The complex acute physiological responses to water immersion suggest swimming may affect BP (blood pressure) differently than other forms of aerobic exercises. We tested the hypothesis that an acute bout of swimming would fail to elicit a PEH BP response compared with an equivalent bout of stationary cycling, regardless of training state. We studied 11 UT and ten triathlon-trained young healthy normotensive [SBP/DBP (systolic BP/diastolic BP) <120/80 mmHg)] men and women (age 23±1 years) who underwent 30 min of intensity-matched cycling and swimming sessions to assess changes in BP during a 75-min seated recovery. CO (cardiac output), SV (stroke volume), TPR (total peripheral resistance), HR (heart rate), HRV (HR variability) and core and skin temperature were also assessed. In UT subjects, PEH was similar between cycling (-3.1±1 mmHg) and swimming (-5.8±1 mmHg), with the greater magnitude of PEH following swimming, reflecting a significant fall in SV between modalities (P<0.05). Trained individuals did not exhibit a PEH response following swimming (0.3±1 mmHg), yet had a significant fall in SBP at 50 min post-cycling exercise (-3.7±1 mmHg) (P<0.05). The absence of PEH after swimming in the trained group may reflect a higher cardiac sympathetic outflow [as indicated by the LF (low-frequency) spectral component of HRV) (25 and 50 min) (P<0.05)] and a slower return of vagal tone, consistent with a significant increase in HR between modalities at all time points (P<0.05). These results suggest that training may limit the potential for an effective post-exertional hypotensive response to aerobic swimming.