The influence of maturation on exercise-induced cardiac remodelling and haematological adaptation.

Cardiovascular and haematological adaptations to endurance training facilitate greater maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ), and such adaptations may be augmented following puberty. Therefore, we compared left ventricular (LV) morphology (echocardiography), blood volume, haemoglobin (Hb) mass (CO rebreathing) and V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ in endurance-trained and untrained boys (n = 42, age = 9.0-17.1 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 61.6 ± 7.2 ml/kg/min, and n = 31, age = 8.0-17.7 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 46.5 ± 6.1 ml/kg/min, respectively) and girls (n = 45, age = 8.2-17.0 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 51.4 ± 5.7 ml/kg/min, and n = 36, age = 8.0-17.6 years, V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$  = 39.8 ± 5.7 ml/kg/min, respectively). Pubertal stage was estimated via maturity offset, with participants classified as pre- or post-peak height velocity (PHV). Pre-PHV, only a larger LV end-diastolic volume/lean body mass (EDV/LBM) for trained boys (+0.28 ml/kg LBM, P = 0.007) and a higher Hb mass/LBM for trained girls (+1.65 g/kg LBM, P = 0.007) were evident compared to untrained controls. Post-PHV, LV mass/LBM (boys: +0.50 g/kg LBM, P = 0.0003; girls: +0.35 g/kg LBM, P = 0.003), EDV/LBM (boys: +0.35 ml/kg LBM, P < 0.0001; girls: +0.31 ml/kg LBM, P = 0.0004), blood volume/LBM (boys: +12.47 ml/kg LBM, P = 0.004; girls: +13.48 ml/kg LBM, P = 0.0002.) and Hb mass/LBM (boys: +1.29 g/kg LBM, P = 0.015; girls: +1.47 g/kg LBM, P = 0.002) were all greater in trained versus untrained groups. Pre-PHV, EDV (R2adj  = 0.224, P = 0.001) in boys, and Hb mass and interventricular septal thickness (R2adj  = 0.317, P = 0.002) in girls partially accounted for the variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ . Post-PHV, stronger predictive models were evident via the inclusion of LV wall thickness and EDV in boys (R2adj  = 0.608, P < 0.0001), and posterior wall thickness and Hb mass in girls (R2adj  = 0.490, P < 0.0001). In conclusion, cardiovascular adaptation to exercise training is more pronounced post-PHV, with evidence for a greater role of central components for oxygen delivery. KEY POINTS: It has long been hypothesised that cardiovascular adaptation to endurance training is augmented following puberty. We investigated whether differences in cardiac and haematological variables exist, and to what extent, between endurance-trained versus untrained, pre- and post-peak height velocity (PHV) children, and how these central factors relate to maximal oxygen consumption. Using echocardiography to quantify left ventricular (LV) morphology and carbon monoxide rebreathing to determine blood volume and haemoglobin mass, we identified that training-related differences in LV morphology are evident in pre-PHV children, with haematological differences also observed between pre-PHV girls. However, the breadth and magnitude of cardiovascular remodelling was more pronounced post-PHV. Cardiac and haematological measures provide significant predictive models for maximal oxygen consumption ( V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ ) in children that are much stronger post-PHV, suggesting that other important determinants within the oxygen transport chain could account for the majority of variance in V̇O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ before puberty.

Exercise-Induced Cardiac Troponin Elevations: From Underlying Mechanisms to Clinical Relevance.

Serological assessment of cardiac troponins (cTn) is the gold standard to assess myocardial injury in clinical practice. A greater magnitude of acutely or chronically elevated cTn concentrations is associated with lower event-free survival in patients and the general population. Exercise training is known to improve cardiovascular function and promote longevity, but exercise can produce an acute rise in cTn concentrations, which may exceed the upper reference limit in a substantial number of individuals. Whether exercise-induced cTn elevations are attributable to a physiological or pathological response and if they are clinically relevant has been debated for decades. Thus far, exercise-induced cTn elevations have been viewed as the only benign form of cTn elevations. However, recent studies report intriguing findings that shed new light on the underlying mechanisms and clinical relevance of exercise-induced cTn elevations. We will review the biochemical characteristics of cTn assays, key factors determining the magnitude of postexercise cTn concentrations, the release kinetics, underlying mechanisms causing and contributing to exercise-induced cTn release, and the clinical relevance of exercise-induced cTn elevations. We will also explain the association with cardiac function, correlates with (subclinical) cardiovascular diseases and exercise-induced cTn elevations predictive value for future cardiovascular events. Last, we will provide recommendations for interpretation of these findings and provide direction for future research in this field.

The influence of barosensory vessel mechanics on the vascular sympathetic baroreflex: insights into aging and blood pressure homeostasis.

Changes in the arterial baroreflex arc contribute to elevated sympathetic outflow and altered reflex control of blood pressure with human aging. Using ultrasound and sympathetic microneurography (muscle sympathetic nerve activity, MSNA) we investigated the relationships between aortic and carotid artery wall tension (indices of baroreceptor activation) and the vascular sympathetic baroreflex operating point (OP; MSNA burst incidence) in healthy, normotensive young (n = 27, 23 ± 3 yr) and middle-aged men (n = 22, 55 ± 4 yr). In young men, the OP was positively related to the magnitude and rate of unloading and time spent unloaded in the aortic artery (r = 0.56, 0.65, and 0.51, P = 0.02, 0.003, and 0.03), but not related to the magnitude or rate of unloading or time spent unloaded in the carotid artery (r = -0.32, -0.07, and 0.06, P = 0.25, 0.81, and 0.85). In contrast, in middle-aged men, the OP was not related to either the magnitude or rate of unloading or time spent unloaded in the aortic (r = 0.22, 0.21, and 0.27, P = 0.41, 0.43, and 0.31) or carotid artery (r = 0.06, 0.28, and -0.01; P = 0.48, 0.25, and 0.98). In conclusion, in young men, aortic unloading mechanics may play a role in determining the vascular sympathetic baroreflex OP. In contrast, in middle-aged men, barosensory vessel unloading mechanics do not appear to determine the vascular sympathetic baroreflex OP and, therefore, do not contribute to age-related arterial baroreflex resetting and increased resting MSNA.NEW & NOTEWORTHY We assessed the influence of barosensory vessel mechanics (magnitude and rate of unloading and time spent unloaded) as a surrogate for baroreceptor unloading. In young men, aortic unloading mechanics are important in regulating the operating point of the vascular sympathetic baroreflex, whereas in middle-aged men, these arterial mechanics do not influence this operating point. The age-related increase in resting muscle sympathetic nerve activity does not appear to be driven by altered baroreceptor input from stiffer barosensory vessels.

Stimulus-specific functional remodeling of the left ventricle in endurance and resistance-trained men.

Left ventricular (LV) structural remodeling following athletic training has been evidenced through training-specific changes in wall thickness and geometry. Whether the LV response to changes in hemodynamic load also adapts in a training-specific manner is unknown. Using echocardiography, we examined LV responses of endurance-trained (n = 15), resistance-trained (n = 14), and nonathletic men (n = 13) to 1) 20, 40, and 60% one repetition-maximum (1RM), leg-press exercise and 2) intravascular Gelofusine infusion (7 mL/kg) with passive leg raise. While resting heart rate was lower in endurance-trained participants versus controls (P = 0.001), blood pressure was similar between groups. Endurance-trained individuals had lower wall thickness but greater LV mass relative to body surface area versus controls, with no difference between resistance-trained individuals and controls. Leg press evoked a similar increase in blood pressure; however, resistance-trained participants preserved stroke volume (SV; -3 ± 8%) versus controls at 60% 1RM (-15 ± 7%, P = 0.001). While the maintenance of SV was related to the change in longitudinal strain across all groups (R = 0.537; P = 0.007), time-to-peak strain was maintained in resistance-trained but delayed in endurance-trained individuals (1 vs. 12% delay; P = 0.021). Volume infusion caused a similar increase in end-diastolic volume (EDV) and SV across groups, but leg raise further increased EDV only in endurance-trained individuals (5 ± 5 to 8 ± 5%; P = 0.018). Correlation analysis revealed a relationship between SV and longitudinal strain following infusion and leg raise (R = 0.334, P = 0.054); however, we observed no between-group differences in longitudinal myocardial mechanics. In conclusion, resistance-trained individuals better maintained SV during pressure loading, whereas endurance-trained individuals demonstrated greater EDV reserve during volume loading. These data provide novel evidence of training-specific LV functional remodeling.NEW & NOTEWORTHY Training-specific functional remodeling of the LV in response to different loading conditions has been recently suggested, but not experimentally tested in the same group of individuals. Our data provide novel evidence of a dichotomous, training-specific LV adaptive response to hemodynamic pressure or volume loading.

FACTORS AFFECTING TEAR PRODUCTION AND INTRAOCULAR PRESSURE IN ANESTHETIZED CHIMPANZEES (PAN TROGLODYTES).

Measurements of intraocular pressure (IOP) and tear production are key components of ophthalmic examination. Chimpanzees (Pan troglodytes) were anesthetized using either tiletamine-zolazepam (TZ; 2 mg/kg) combined with medetomidine (TZM; 0.02 mg/kg), or, TZ alone (6mg/kg). Tear production was lower (P = 0.03) with TZM (5.63 ± 6.22 mm/min; n = 16) than with TZ (11.13 ± 4.63 mm/min; n = 8). Mean IOP, measured using rebound tonometry in an upright body position (n = 8) was 18.74 ± 3.01 mm Hg, with no differences between right and left eyes. However, positioning chimpanzees in left lateral recumbency (n = 27) resulted in higher IOP in the dependent (left) eye (24.77 ± 4.49 mm Hg) compared to the nondependent (right) eye (22.27 ± 4.65 mm Hg) of the same animal (P < 0.0001). These data indicate medetomidine anesthesia markedly lowers tear production in chimpanzees, and that body position should be taken into consideration when performing rebound tonometry.

Upward resetting of the vascular sympathetic baroreflex in middle-aged male runners.

This study focused on the influence of habitual endurance exercise training (i.e., committed runner or nonrunner) on the regulation of muscle sympathetic nerve activity (MSNA) and arterial pressure in middle-aged (50 to 63 yr, n = 23) and younger (19 to 30 yr; n = 23) normotensive men. Hemodynamic and neurophysiological assessments were performed at rest. Indices of vascular sympathetic baroreflex function were determined from the relationship between spontaneous changes in diastolic blood pressure (DBP) and MSNA. Large vessel arterial stiffness and left ventricular stroke volume also were measured. Paired comparisons were performed within each age category. Mean arterial pressure and basal MSNA bursts/min were not different between age-matched runners and nonrunners. However, MSNA bursts/100 heartbeats, an index of baroreflex regulation of MSNA (vascular sympathetic baroreflex operating point), was higher for middle-aged runners (P = 0.006), whereas this was not different between young runners and nonrunners. The slope of the DBP-MSNA relationship (vascular sympathetic baroreflex gain) was not different between groups in either age category. Aortic pulse wave velocity was lower for runners of both age categories (P < 0.03), although carotid ß-stiffness was lower only for middle-aged runners (P = 0.04). For runners of both age categories, stroke volume was larger, whereas heart rate was lower (both P < 0.01). In conclusion, we suggest that neural remodeling and upward setting of the vascular sympathetic baroreflex compensates for cardiovascular adaptations after many years committed to endurance exercise training, presumably to maintain arterial blood pressure stability. NEW & NOTEWORTHY Exercise training reduces muscle sympathetic burst activity in disease; this is often extrapolated to infer a similar effect in health. We demonstrate that burst frequency of middle-aged and younger men committed to endurance training is not different compared with age-matched casual exercisers. Notably, well-trained, middle-aged runners display similar arterial pressure but higher sympathetic burst occurrence than untrained peers. We suggest that homeostatic plasticity and upward setting of the vascular sympathetic baroreflex maintains arterial pressure stability following years of training.

Influence of vagal control on sex-related differences in left ventricular mechanics and hemodynamics.

Left ventricular (LV) twist mechanics differ between men and women during acute physiological stress, which may be partly mediated by sex differences in autonomic control. While men appear to have greater adrenergic control of LV twist, the potential contribution of vagal modulation to sex differences in LV twist remains unknown. Therefore, the present study examined the role of vagal control on sex differences in LV twist during graded lower body negative pressure (LBNP) and supine cycling. On two separate visits, LV mechanics were assessed using two-dimensional speckle-tracking echocardiography in 18 men (22 ± 2 yr) and 17 women (21 ± 4 yr) during -40- and -60-mmHg LBNP and 25% and 50% of peak supine cycling workload with and without glycopyrrolate (vagal blockade). LV twist was not different at baseline but was greater in women during -60 mmHg in both control (women: 16.0 ± 3.4° and men: 12.9 ± 2.3°, P = 0.004) and glycopyrrolate trials (women: 17.7 ± 5.9° and men: 13.9 ± 3.3°, P < 0.001) due to greater apical rotation during control (women: 11.9 ± 3.6° and men: 7.8 ± 1.5°, P < 0.001) and glycopyrrolate (women: 11.6 ± 4.9° and men: 7.1 ± 3.6°, P = 0.009). These sex differences in LV twist consistently coincided with a greater LV sphericity index (i.e., ellipsoid geometry) in women compared with men. In contrast, LV twist did not differ between the sexes during exercise with or without glycopyrrolate. In conclusion, women have augmented LV twist compared with men during large reductions to preload, even during vagal blockade. As such, differences in vagal control do not appear to contribute to sex differences in the LV twist responses to physiological stress, but they may be related to differences in ventricular geometry. NEW & NOTEWORTHY This is the first study to specifically examine the role of vagal autonomic control on sex-related differences in left ventricular (LV) mechanics. Contrary to our hypothesis, vagal control does not appear to primarily determine sex differences in LV mechanical or hemodynamic responses to acute physiological stress. Instead, differences in LV geometry may be a more important contributor to sex differences in LV mechanics.

The effect of an aerobic exercise bout 24 h prior to each doxorubicin treatment for breast cancer on markers of cardiotoxicity and treatment symptoms: a RCT.

PURPOSE: In rodents, a single exercise bout performed 24 h prior to a single doxorubicin treatment provides cardio-protection. This study investigated whether performing this intervention prior to every doxorubicin treatment for breast cancer reduced subclinical cardiotoxicity and treatment symptoms. METHODS: Twenty-four women with early stage breast cancer were randomly assigned to perform a 30-min, vigorous-intensity treadmill bout 24 h prior to each of four doxorubicin-containing chemotherapy treatments or to usual care. Established echocardiographic and circulating biomarkers of subclinical cardiotoxicity, as well as blood pressure and body weight were measured before the first and 7-14 days after the last treatment. The Rotterdam symptom checklist was used to assess patient-reported symptoms. RESULTS: The exercise and usual care groups did not differ in the doxorubicin-related change in longitudinal strain, twist, or cardiac troponin. However, the four total exercise bouts prevented changes in hemodynamics (increased cardiac output, resting heart rate, decreased systemic vascular resistance, p < 0.01) and reduced body weight gain, prevalence of depressed mood, sore muscles, and low back pain after the last treatment (p < 0.05) relative to the usual care group. No adverse events occurred. CONCLUSIONS: An exercise bout performed 24 h prior to every doxorubicin treatment did not have an effect on markers of subclinical cardiotoxicity, but had a positive systemic effect on hemodynamics, musculoskeletal symptoms, mood, and body weight in women with breast cancer. A single exercise bout prior to chemotherapy treatments may be a simple clinical modality to reduce symptoms and weight gain among women with breast cancer.

The influence of adrenergic stimulation on sex differences in left ventricular twist mechanics.

KEY POINTS: Sex differences in left ventricular (LV) mechanics occur during acute physiological challenges; however, it is unknown whether sex differences in LV mechanics are fundamentally regulated by differences in adrenergic control. Using two-dimensional echocardiography and speckle tracking analysis, this study compared LV mechanics in males and females matched for LV length during post-exercise ischaemia (PEI) and ß1 -adrenergic receptor blockade. Our data demonstrate that while basal rotation was increased in males, LV twist was not significantly different between the sexes during PEI. In contrast, during ß1 -adrenergic receptor blockade, LV apical rotation, twist and untwisting velocity were reduced in males compared to females. Significant relationships were observed between LV twist and LV internal diameter and sphericity index in females, but not males. These findings suggest that LV twist mechanics may be more sensitive to alterations in adrenergic stimulation in males, but more highly influenced by ventricular structure and geometry in females. ABSTRACT: Sex differences in left ventricular (LV) mechanics exist at rest and during acute physiological stress. Differences in cardiac autonomic and adrenergic control may contribute to sex differences in LV mechanics and LV haemodynamics. Accordingly, this study aimed to investigate sex differences in LV mechanics with altered adrenergic stimulation achieved through post-handgrip-exercise ischaemia (PEI) and ß1 -adrenergic receptor (AR) blockade. Twenty males (23 ± 5 years) and 20 females (22 ± 3 years) were specifically matched for LV length (males: 8.5 ± 0.5 cm, females: 8.2 ± 0.6 cm, P = 0.163), and two-dimensional speckle-tracking echocardiography was used to assess LV structure and function at baseline, during PEI and following administration of 5 mg bisoprolol (ß1 -AR antagonist). During PEI, LV end-diastolic volume and stroke volume were increased in both groups (P < 0.001), as was end-systolic wall stress (P < 0.001). LV twist and apical rotation were not altered from baseline or different between the sexes; however, basal rotation increased in males (P = 0.035). During ß1 -AR blockade, LV volumes were unchanged but blood pressure and heart rate were reduced in both groups (P < 0.001). LV apical rotation (P = 0.036) and twist (P = 0.029) were reduced in males with ß1 -AR blockade but not females, resulting in lower apical rotation (males: 6.8 ± 2.1 deg, females: 8.8 ± 2.3 deg, P = 0.007) and twist (males: 8.6 ± 1.9 deg, females: 10.7 ± 2.8 deg, P = 0.008), and slower untwisting velocity (males: 68.2 ± 22.1 deg s-1 , females: 82.0 ± 18.7 deg s-1 , P = 0.046) compared to females. LV twist mechanics are reduced in males compared to females during reductions to adrenergic stimulation, providing preliminary evidence that LV twist mechanics may be more sensitive to adrenergic control in males than in females.

HEART RATE AND INDIRECT BLOOD PRESSURE RESPONSES TO FOUR DIFFERENT FIELD ANESTHETIC PROTOCOLS IN WILD-BORN CAPTIVE CHIMPANZEES (PAN TROGLODYTES).

Limited data are available on hemodynamic responses to anesthetic protocols in wild-born chimpanzees (Pan troglodytes). Accordingly, this study characterized the heart rate (HR) and blood pressure responses to four anesthetic protocols in 176 clinically healthy, wild-born chimpanzees undergoing routine health assessments. Animals were anesthetized with medetomidine-ketamine (MK) (n = 101), tiletamine-zolazepam (TZ) (n = 30), tiletamine-zolazepam-medetomidine (TZM) (n = 24), or medetomidine-ketamine (maintained with isoflurane) (MKI) (n = 21). During each procedure, HR, systolic blood pressure (SBP), and diastolic blood pressure (DBP) were regularly recorded. Data were grouped according to anesthetic protocol, and mean HR, SBP, and DBP were calculated. Differences between mean HR, SBP, and DBP for each anesthetic protocol were assessed using the Kruskall-Wallis test and a Dunn multiple comparisons post hoc analysis. To assess the hemodynamic time course response to each anesthetic protocol, group mean data (±95% confidence interval [CI]) were plotted against time postanesthetic induction. Mean HR (beats/min [CI]) was significantly higher in TZ (86 [80-92]) compared to MKI (69 [61-78]) and MK (62 [60-64]) and in TZM (73 [68-78]) compared to MK. The average SBP and DBP values (mm Hg [CI]) were significantly higher in MK (130 [126-134] and 94 [91-97]) compared to TZ (104 [96-112] and 58 [53-93]) and MKI (113 [103-123] and 78 [69-87]) and in TZM (128 [120-135] and 88 [83-93]) compared to TZ. Time course data were markedly different between protocols, with MKI showing the greatest decline over time. Both the anesthetic protocol adopted and the timing of measurement after injection influence hemodynamic recordings in wild-born chimpanzees and need to be considered when monitoring or assessing cardiovascular health.

Left ventricular twist mechanics in the context of normal physiology and cardiovascular disease: a review of studies using speckle tracking echocardiography.

The anatomy of the adult human left ventricle (LV) is the result of its complex interaction with its environment. From the fetal to the neonatal to the adult form, the human LV undergoes an anatomical transformation that finally results in the most complex of the four cardiac chambers. In its adult form, the human LV consists of two muscular helixes that surround the midventricular circumferential layer of muscle fibers. Contraction of these endocardial and epicardial helixes results in a twisting motion that is thought to minimize the transmural stress of the LV muscle. In the healthy myocardium, the LV twist response to stimuli that alter preload, afterload, or contractility has been described and is deemed relatively consistent and predictable. Conversely, the LV twist response in patient populations appears to be a little more variable and less predictable, yet it has revealed important insight into the effect of cardiovascular disease on LV mechanical function. This review discusses important methodological aspects of assessing LV twist and evaluates the LV twist responses to the main physiological and pathophysiological states. It is concluded that correct assessment of LV twist mechanics holds significant potential to advance our understanding of LV function in human health and cardiovascular disease.

Females have greater left ventricular twist mechanics than males during acute reductions to preload.

Compared to males, females have smaller left ventricular (LV) dimensions and volumes, higher ejection fractions (EF), and higher LV longitudinal and circumferential strain. LV twist mechanics determine ventricular function and are preload-dependent. Therefore, the sex differences in LV structure and myocardial function may result in different mechanics when preload is altered. This study investigated sex differences in LV mechanics during acute challenges to preload. With the use of conventional and speckle-tracking echocardiography, LV structure and function were assessed in 20 males (24 ± 6.2 yr) and 20 females (23 ± 3.1 yr) at baseline and during progressive levels of lower body negative pressure (LBNP). Fourteen participants (8 males, 6 females) were also assessed following a rapid infusion of saline. LV end-diastolic volume, end-systolic volume, stroke volume (SV), and EF were reduced in both groups during LBNP (P < 0.001). While males had greater absolute volumes (P < 0.001), there were no sex differences in allometrically scaled volumes at any stage. Sex differences were not detected at baseline in basal rotation, apical rotation, or twist. Apical rotation and twist increased in both groups (P < 0.001) with LBNP. At -60 mmHg, females had greater apical rotation (P = 0.009), twist (P = 0.008), and torsion (P = 0.002) and faster untwisting velocity (P = 0.02) than males. There were no differences in mechanics following saline infusion. Females have larger LV twist and a faster untwisting velocity than males during large reductions to preload, supporting that females have a greater reliance on LV twist mechanics to maintain SV during severe reductions to preload.

Left ventricular trabeculation in Hominidae: divergence of the human cardiac phenotype.

Although the gross morphology of the heart is conserved across mammals, subtle interspecific variations exist in the cardiac phenotype, which may reflect evolutionary divergence among closely-related species. Here, we compare the left ventricle (LV) across all extant members of the Hominidae taxon, using 2D echocardiography, to gain insight into the evolution of the human heart. We present compelling evidence that the human LV has diverged away from a more trabeculated phenotype present in all other great apes, towards a ventricular wall with proportionally greater compact myocardium, which was corroborated by post-mortem chimpanzee (Pan troglodytes) hearts. Speckle-tracking echocardiographic analyses identified a negative curvilinear relationship between the degree of trabeculation and LV systolic twist, revealing lower rotational mechanics in the trabeculated non-human great ape LV. This divergent evolution of the human heart may have facilitated the augmentation of cardiac output to support the metabolic and thermoregulatory demands of the human ecological niche.

Aortic stiffness contributes to greater pressor responses during static hand grip exercise in healthy young and middle-aged normotensive men.

Central arterial stiffness can influence exercise blood pressure (BP) by increasing the rise in arterial pressure per unit increase in aortic inflow. Whether central arterial stiffness influences the pressor response to isometric handgrip exercise (HG) and post-exercise muscle ischemia (PEMI), two common laboratory tests to study sympathetic control of BP, is unknown. We studied 46 healthy non-hypertensive males (23 young and 23 middle-aged) during HG (which increases in cardiac output [Q̇c]) and isolated metaboreflex activation PEMI (no change or decreases in Q̇c). Aortic stiffness (aortic pulse wave velocity [aPWV]; applanation tonometry via SphygmoCor) was measured during supine rest and was correlated to the pressor responses to HG and PEMI. BP (photoplethysmography) and muscle sympathetic nerve activity (MSNA) were continuously recorded at rest, during HG to fatigue (35 % maximal voluntary contraction) and 2-min of PEMI. aPWV was higher in middle-aged compared to young males (7.1 ± 0.9 vs 5.4 ± 0.7 m/s, P < 0.001). Middle-aged males also exhibited greater increases in systolic pressure (∆30 ± 11 vs 10 ± 8 mmHg) and MSNA (∆2313 ± 2006 vs 1387 ± 1482 %/min) compared to young males during HG (both, P < 0.03); with no difference in the Q̇c response (P = 0.090). Responses to PEMI were not different between groups. Sympathetic transduction during these stressors (MSNA-diastolic pressure slope) was not different between groups (P > 0.341). Middle-aged males displayed a greater increase in SBP per unit change of Q̇c during HG (∆SBP/∆Q̇c; 21 ± 18 vs 6 ± 10 mmHg/L/min, P = 0.004), with a strong and moderate relationship between the change in systolic (r = 0.53, P < 0.001) and diastolic pressure (r = 0.34, P = 0.023) and resting aPWV, respectively; with no correlation during PEMI. Central arterial stiffness can modulate pressor responses during stimuli associated with increases in cardiac output and sympathoexcitation in healthy males.

Adaptation of Left Ventricular Twist Mechanics in Exercise-Trained Children Is Only Evident after the Adolescent Growth Spurt.

BACKGROUND: The extent of structural cardiac remodeling in response to endurance training is maturity dependent. In adults, this structural adaptation is often associated with the adaptation of left ventricular (LV) twist mechanics. For example, an increase in LV twist often follows an expansion in end-diastolic volume, whereas a reduction in twist may follow a thickening of the LV walls. While structural cardiac remodeling has been shown to be more prominent post-peak height velocity (PHV), it remains to be determined how this maturation-dependent structural remodeling influences LV twist. Therefore, we aimed to (1) compare LV twist mechanics between trained and untrained children pre- and post-PHV and (2) investigate how LV structural variables relate to LV twist mechanics pre- and post-PHV. METHODS: Left ventricular function and morphology were assessed (echocardiography) in endurance-trained and untrained boys (n = 38 and n = 28, respectively) and girls (n = 39 and n = 34, respectively). Participants were categorized as either pre- or post-PHV using maturity offset to estimate somatic maturation. RESULTS: Pre-PHV, there were no differences in LV twist or torsion between trained and untrained boys (twist: P = .630; torsion: P = .382) or girls (twist: P = .502; torsion: P = .316), and LV twist mechanics were not related with any LV structural variables (P > .05). Post-PHV, LV twist was lower in trained versus untrained boys (P = .004), with torsion lower in trained groups, irrespective of sex (boys: P < .001; girls: P = .017). Moreover, LV torsion was inversely related to LV mass (boys: r = -0.55, P = .001; girls: r = -0.46, P = .003) and end-diastolic volume (boys: r = -0.64, P < .001; girls: r = -0.36, P = .025) in both sexes. CONCLUSIONS: A difference in LV twist mechanics between endurance-trained and untrained cohorts is only apparent post-PHV, where structural and functional remodeling were related.

The endurance athletes heart: acute stress and chronic adaptation.

The impact of endurance exercise training on the heart has received significant research and clinical attention for well over a century. Despite this, many issues remain controversial and clinical interpretation can be complex of biomarkers of cardiomyocyte insult. This review assesses the current state of knowledge related to two areas of research where problems with clinical decision making may arise: (1) the impact of chronic endurance exercise training on cardiac structure, function and electrical activity to the point where the athletic heart phenotype may be similar to the expression of some cardiac pathologies (a diagnostic dilemma referred to as the 'grey-zone') and (2) the impact of acute bouts of prolonged exercise on cardiac function and the presentation of biomarkers and cardiomyocyte insult in the circulatory system. The combination of acute endurance exercise stress on the heart and prolonged periods of training are considered together in the final section.

Cardiac Responses to Submaximal Isometric Contraction and Aerobic Exercise in Healthy Pregnancy.

PURPOSE: The increased physiological demand of pregnancy results in the profound adaptation of the maternal cardiovascular system, reflected by greater resting cardiac output and left ventricular (LV) deformation. Whether the increased resting demand alters acute cardiac responses to exercise in healthy pregnant women is not well understood. METHODS: Healthy nonpregnant (n = 18), pregnant (n = 14, 22-26 wk gestation), and postpartum women (n = 13, 12-16 wk postdelivery) underwent assessments of cardiac function and LV mechanics at rest, during a sustained isometric forearm contraction (30% maximum), and during low-intensity (LOW) and moderate-intensity (MOD) dynamic cycling exercise (25% and 50% peak power output). Significant differences (α = 0.05) were determined using ANCOVA and general linear model (resting value included as covariate). RESULTS: When accounting for higher resting cardiac output in pregnant women, pregnant women had greater cardiac output during isometric contraction (2.0 ± 0.3 L·min-1·m-1.83; nonpregnant, 1.3 ± 0.2 L·min-1·m-1.83; postpartum, 1.5 ± 0.5 L·min-1·m-1.83; P = 0.02) but similar values during dynamic cycling exercise (pregnant, LOW = 2.8 ± 0.4 L·min-1·m-1.83, MOD = 3.4 ± 0.7 L·min-1·m-1.83; nonpregnant, LOW = 2.4 ± 0.3 L·min-1·m-1.83, MOD = 3.0 ± 0.3 L·min-1·m-1.83; postpartum, LOW = 2.3 ± 0.4 L·min-1·m-1.83, MOD = 3.0 ± 0.5 L·min-1·m-1.83; P = 0.96). Basal circumferential strain was higher in pregnant women at rest, during the sustained isometric forearm contraction (-23.5% ± 1.2%; nonpregnant, -14.6% ± 1.4%; P = 0.001), and during dynamic cycling exercise (LOW = -27.0% ± 4.9%, MOD = -27.4% ± 4.6%; nonpregnant, LOW = -15.8% ± 4.5%, MOD = -15.2% ± 6.7%; P = 0.012); however, other parameters of LV mechanics were not different between groups. CONCLUSION: The results support that the maternal heart can appropriately respond to additional cardiac demand and altered loading experienced during acute isometric and dynamic exercise, although subtle differences in responses to these challenges were observed. In addition, the LV mechanics that underpin global cardiac function are greater in pregnant women during exercise, leading to the speculation that the hormonal milieu of pregnancy influences regional deformation.

Right Ventricular Function and Region-Specific Adaptation in Athletes Engaged in High-Dynamic Sports: A Meta-Analysis.

BACKGROUND: Structural remodeling of the right ventricle (RV) is widely documented in athletes. However, functional adaptation, including RV pressure generation and systolic free-wall longitudinal mechanics, remains equivocal. This meta-analysis compared RV pressure and function in athletes and controls. METHODS: A systematic review of online databases was conducted up to June 4, 2020. Meta-analyses were performed on RV systolic pressures, at rest and during exercise, tricuspid annular plane systolic displacement, myocardial velocity (S'), and global and regional longitudinal strain. Bias was assessed using Egger regression for asymmetry. Data were analyzed using random-effects models with weighted mean difference and 95% CI. RESULTS: Fifty-three studies were eligible for inclusion. RV systolic pressure was obtained from 21 studies at rest (n=1043:1651; controls:athletes) and 8 studies during exercise (n=240:495) and was significantly greater in athletes at rest (weighted mean difference, 2.9 mmHg [CI, 1.3-4.5 mmHg]; P=0.0005) and during exercise (11.0 [6.5-15.6 mm Hg]; P<0.0001) versus controls. Resting tricuspid annular plane systolic displacement (P<0.0001) and S' (P=0.001) were greater in athletes. In contrast, athletes had similar RV free-wall longitudinal strain (17 studies; n=450:605), compared with controls but showed greater longitudinal apical strain (16 studies; n=455:669; 0.9%, 0.1%-1.8%; P=0.03) and lower basal strain (-2.5% [-1.4 to -3.5%]; P<0.0001). CONCLUSIONS: Functional RV adaptation, characterized by increased tricuspid annular displacement and velocity and a greater base-to-apex strain gradient, is a normal feature of the athlete's heart, together with a slightly elevated RV systolic pressure. These findings contribute to our understanding of RV in athletes and highlight the importance of considering RV function in combination with structure in the clinical interpretation of the athlete's heart.

Diastolic function in healthy humans: non-invasive assessment and the impact of acute and chronic exercise.

Left ventricular (LV) diastolic function is important because the enhanced systolic function that underpins high levels of cardio-respiratory fitness has to be matched by changes in LV filling, and LV diastolic dysfunction plays a key early role in the development and progression of a myriad of cardiovascular diseases. This review serves to detail knowledge in relation to: (1) the definition of diastole and the mechanical processes that occur during the diastolic period, (2) the quantitative assessment of diastolic function, predominantly focusing on non-invasive echocardiographic imaging modes such as tissue Doppler imaging and deformation analysis, (3) the impact of acute aerobic exercise on diastolic function, from the augmentation of function necessary to meet the demand for an increased cardiac output at exercise onset, to current concerns related to the impact of prolonged or ultra-endurance activity on diastolic function during recovery, (4) the adaptation in diastolic function observed with chronic aerobic exercise training in athletes and sedentary individuals who undergo training programmes, and (5) directions for future research.

Electrocardiographic changes following six months of long-distance triathlon training in previously recreationally active individuals.

Background: Clinical electrocardiographic (ECG) guidelines for athlete's heart are based upon cross-sectional data. We aimed to longitudinally evaluate the influence of endurance training on the ECG and compare the prevalence of ECG abnormalities defined by contemporary criteria. Methods: A group of 66 training-naïve individuals completed a six-month training programme with resting ECGs and cardiopulmonary exercise tests performed at baseline, two and six months. Data were analysed using repeated measures analysis of variance and the prevalence of ECG abnormalities compared between proposed criteria. Results : Maximal oxygen consumption increased from 45.4 ± 7.1 to 50.3 ± 7.1 ml·kg-1·min-1 (p < 0.05) pre-to-post training. ECG changes included, bradycardia (60 ± 12 vs. 53 ± 8 beats·min-1; p < 0.05), shorter P wave duration (106 ± 10 vs. 103 ± 11 ms; p < 0.05), reduced QTc (413 ± 27 vs. 405 ± 22 ms; p < 0.05), and increased left ventricular Sokolow-Lyon index (2.45 ± 0.66 vs. 2.62 ± 0.78 mV; p < 0.05). 85% of individuals showed ≥1 'training-related' ECG finding at six months vs. 68% at baseline. Using the 2013 Seattle Criteria, 4 ECGs were 'abnormal' at baseline and 3 at month six vs. 2 at baseline and 1 at month six, using the 2017 International Consensus. Prevalence of 'borderline' findings did not increase with training (11% at baseline and six months). Conclusion: Six-months endurance training leads to a greater prevalence of 'training-related' but not 'borderline' or 'training-unrelated' ECGs. 'Borderline findings' may not necessarily represent training-related cardiac remodelling in novice athletes following a six-month training intervention. KEY MESSAGES This study aimed to assess the longitudinal ECG changes following six months of endurance training, in training-naïve individuals, and whether these ECG changes support the revisions made to the recent 2017 international consensus criteria. The prevalence of 'training-related' findings were increased with six months of endurance training, however the prevalence of the revised 'borderline' criteria, according to the 2017 international consensus, did not increase and the associated quantitative ECG data (e.g. P-wave amplitude, QRS axis and QRS duration) remained unchanged. Further clinical consideration may be warranted for individuals within the early phase of exercise engagement presenting with 'borderline' ECG abnormalities, defined by the International criteria.