Intrathoracic pressure modulates cardiac loading conditions, which then influence left ventricular (LV) chamber function, and may occur with underlying myocardial mechanical alterations. We investigated the independent effects of inspiratory negative and expiratory positive intrathoracic pressure on septal geometry, LV chamber function, and rotation, twist, and strain indices. After baseline, 20 healthy adults (11M/9F, 23 ± 4 yr) performed resistive breathing to manipulate inspiratory (-30, -20, -10 cmH2O) or expiratory (+10, +20 cmH2O) intrathoracic pressure. Echocardiography was used to acquire LV-focused two-dimensional (2-D) images, and mitral Doppler inflow and annular tissue velocity spectra. Images were analyzed for LV chamber volumes, tissue velocities, transmitral filling velocities, and speckle tracking-derived LV longitudinal, radial, and circumferential strain and strain-rate, basal and apical rotation, and twist. Across negative pressure trials, most profoundly at -30 cmH2O, we observed progressive end-diastolic septal flattening (3.9 ± 0.4 vs. 3.2 ± 0.4 cm, P < 0.05) and decreases in LV end-diastolic volume (103 ± 23 vs. 115 ± 25 mL, P < 0.05) and stroke volume, whereas end-systolic volume was unchanged. However, LV apical and basal rotation, twist (13.3° ± 3.6° vs. 13.9° ± 3.7°, P = 0.890), and circumferential, radial, and longitudinal strain indices were largely unchanged. During positive pressure trials, we observed main effects for septal flattening (P = 0.014) confined to inspiration, and modestly reduced LV end-diastolic volume (P < 0.001), end-systolic volume (P = 0.033), and stroke volume. Again, myocardial mechanics parameters changed little. Collectively, our data suggest that both positive and negative intrathoracic pressures can exacerbate direct ventricular interaction through opposing mechanisms that attenuate LV end-diastolic volume and stroke volume, but without specific changes in myocardial mechanics or mitral inflow.NEW & NOTEWORTHY Incrementally more negative or positive intrathoracic pressures, relative to normal dynamic breathing, progressively attenuate left ventricular end-diastolic volume and stroke volume in healthy younger adults. Incrementally more negative or positive intrathoracic pressures were each associated with progressive septal flattening during inspiration, indicating direct ventricular interaction. However, left ventricular transmitral inflow velocities, and myocardial rotation, twist, and circumferential, longitudinal, and radial strain parameters changed little.

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.

Objective: To perform a cost-effectiveness analysis of high-intensity interval training (HIIT) compared with moderate intensity steady-state (MISS) training in people with coronary artery disease (CAD) attending cardiac rehabilitation (CR). Design: Secondary cost-effectiveness analysis of a prospective, assessor-blind, parallel group, multi-center RCT. Setting: Six outpatient National Health Service cardiac rehabilitation centers in England and Wales, UK. Participants: 382 participants with CAD (N=382). Interventions: Participants were randomized to twice-weekly usual care (n=195) or HIIT (n=187) for 8 weeks. Usual care was moderate intensity continuous exercise (60%-80% maximum capacity, MISS), while HIIT consisted of 10 pound 1-minute intervals of vigorous exercise (>85% maximum capacity) interspersed with 1-minute periods of recovery. Main Outcome Measures: We conducted a cost-effectiveness analysis of the HIIT or MISS UK trial. Health related quality of life was measured with the EQ-5D-5L to estimate quality-adjusted life years (QALYs). Costs were estimated with health service resource use and intervention delivery costs. Cost-utility analysis measured the incremental cost-effectiveness ratio (ICER). Bootstrapping assessed the probability of HIIT being cost-effective according to the UK National Institute for Health and Care Excellence (NICE) threshold value (20,000 pound per QALY). Missing data were imputed. Uncertainty was estimated using probabilistic sensitivity analysis. Assumptions were tested using univariate/1-way sensitivity analysis. Results: 124 (HIIT, n=59; MISS, n=65) participants completed questionnaires at baseline, 8 weeks, and 12 months. Mean combined health care use and delivery cost was 676 pound per participant for HIIT, and 653 pound for MISS. QALY changes were 0.003 and-0.013, respectively. For complete cases, the ICER was 1448 pound per QALY for HIIT compared with MISS. At a willingness-to-pay threshold of 20,000 pound per QALY, the probability of HIIT being cost-effective was 96% (95% CI, 0.90 to 0.95). Conclusion: For people with CAD attending CR, HIIT was cost-effective compared with MISS. These findings are important to policy makers, commissioners, and service providers across the health care sector.

ObjectiveTo compare the characteristics of “responders” and “non-responders” to 8-weeks of exercise training to determine differences in key cardiovascular disease outcomes in people with coronary artery disease (CAD).DesignSecondary analysis of data from the HIIT or MISS UK trial.SettingSix outpatient National Health Service cardiac rehabilitation centers in the UK. In people with CAD attending cardiac rehabilitation, the HIIT or MISS UK trial reported that short-term, low-volume, high intensity interval training (HIIT) was more effective than moderate intensity steady state (MISS) exercise training for improving peak oxygen uptake (VO2peak).Participants382 participants with CAD (mean age: 58.8 ± 9.6 years; mean BMI: 29.0 ± 4.3 kg∙m−2).Main Outcome MeasuresWe identified “responders” and “non-responders” based on a meaningful change in peak oxygen uptake, using two established methods. Key clinical, quality of life, and cardiopulmonary exercise test (CPET)-derived outcomes were compared between groups.ResultsResponders were more likely to be younger (P<0.05), and demonstrate greater improvement in CPET-related outcomes e.g. oxygen uptake efficiency slope (OUES), ventilatory efficiency (VE/VCO2 slope), and peak power output (all comparisons, P<0.001). Responders were more likely to observe improvements in quality of life (EQ-5D-5L; mean Δ 13.6 v mean Δ 9.4; P=0.045), and HDL-cholesterol (mean Δ 0.09 mmol.L−1 v mean Δ 0.04 mmol.L−1; P=0.004), compared to non-responders.ConclusionsIn people with CAD attending cardiac rehabilitation, “responders” to exercise training were more likely to be younger, and demonstrate greater improvements in health-related QoL and HDL-cholesterol.

Cardiopulmonary exercise testing (CPET) is the 'gold standard' method for evaluating functional capacity, with oxygen pulse (O2Pulse) inflections serving as a potential indicator of myocardial ischaemia. However, the reliability and agreement of identifying these inflections have not been thoroughly investigated. This study aimed to assess the inter- and intra-observer reliability and agreement of a subjective quantification method for identifying O2Pulse inflections during CPET, and to propose a more robust and objective novel algorithm as an alternative methodology. A retrospective analysis was conducted using baseline data from the HIIT or MISS UK trial. The O2Pulse curves were visually inspected by two independent examiners, and compared against an objective algorithm. Fleiss' Kappa was used to determine the reliability of agreement between the three groups of observations. The results showed almost perfect agreement between the algorithm and both examiners, with a Fleiss' Kappa statistic of 0.89. The algorithm also demonstrated excellent inter-rater reliability (ICC) when compared to both examiners (0.92-0.98). However, a significant level (P ≤0.05) of systematic bias was observed in Bland-Altman analysis for comparisons involving the novice examiner. In conclusion, this study provides evidence for the reliability of both subjective and novel objective methods for identifying inflections in O2Pulse during CPET. These findings suggest that further research into the clinical significance of O2Pulse inflections is warranted, and that the adoption of a novel objective means of quantification may be preferable to ensure equality of outcome for patients.

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.

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.

BackgroundThere is a lack of international consensus regarding the prescription of high-intensity interval training (HIIT) for people with coronary artery disease (CAD) attending cardiac rehabilitation (CR).AimsTo assess the clinical effectiveness and safety of low-volume HIIT compared with moderate-intensity steady-state (MISS) exercise training for people with CAD.Methods and resultsWe conducted a multi-centre RCT, recruiting 382 patients from 6 outpatient CR centres. Participants were randomized to twice-weekly HIIT (n = 187) or MISS (n = 195) for 8 weeks. HIIT consisted of 10 x 1 min intervals of vigorous exercise (> 85% maximum capacity) interspersed with 1 min periods of recovery. MISS was 20-40 min of moderate-intensity continuous exercise (60-80% maximum capacity). The primary outcome was the change in cardiorespiratory fitness [peak oxygen uptake (VO2 peak)] at 8 week follow-up. Secondary outcomes included cardiovascular disease risk markers, cardiac structure and function, adverse events, and health-related quality of life. At 8 weeks, VO2 peak improved more with HIIT (2.37 mL.kg(-1).min(-1); SD, 3.11) compared with MISS (1.32 mL.kg(-1).min(-1); SD, 2.66). After adjusting for age, sex, and study site, the difference between arms was 1.04 mL.kg(-1).min(-1) (95% CI, 0.38 to 1.69; P = 0.002). Only one serious adverse event was possibly related to HIIT.ConclusionsIn stable CAD, low-volume HIIT improved cardiorespiratory fitness more than MISS by a clinically meaningful margin. Low volume HIIT is a safe, well-tolerated, and clinically effective intervention that produces short-term improvement in cardiorespiratory fitness. It should be considered by all CR programmes as an adjunct or alternative to MISS.

In healthy younger adults, the Mueller maneuver transiently reduces left atrial filling and passive emptying during the reservoir and conduit phases, respectively. Corresponding reductions are seen in left atrial reservoir and conduit phase longitudinal myocardial strain and strain rate. However, left atrial pump phase active function and mechanics are largely preserved compared with baseline. Rapid changes in LA chamber volumes and myocardial strain with recurrent forceful inspiratory efforts and relaxation may reflect acute LA stress.

Captive chimpanzees (Pan troglodytes) mature earlier in body mass and have a greater growth rate compared to wild individuals. However, relatively little is known about how growth parameters compare between chimpanzees living in different captive environments. To investigate, body mass was measured in 298 African sanctuary chimpanzees and was acquired from 1030 zoological and 442 research chimpanzees, using data repositories. An analysis of covariance, adjusting for age, was performed to assess same-sex body mass differences between adult sanctuary, zoological, and research populations. Piecewise linear regression was performed to estimate sex-specific growth rates and the age at maturation, which were compared between sexes and across populations using extra-sum-of-squares F tests. Adult body mass was greater in the zoological and resarch populations compared to the sanctuary chimpanzees, in both sexes. Male and female sanctuary chimpanzees were estimated to have a slower rate of growth compared with their zoological and research counterparts. Additionally, male sanctuary chimpanzees were estimated to have an older age at maturation for body mass compared with zoological and research males, whereas the age at maturation was similar across female populations. For both the zoological and research populations, the estimated growth rate was greater in males compared to females. Together, these data contribute to current understanding of growth and maturation in this species and suggest marked differences between the growth patterns of chimpanzees living in different captive environments.

Cardiovascular and haematological adaptations to endurance training facilitate greater maximal oxygen consumption (V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$), and such adaptations may be augmented following puberty. Therefore, we compared left ventricular (LV) morphology (echocardiography), blood volume, haemoglobin (Hb) mass (CO rebreathing) and V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ in endurance-trained and untrained boys (n = 42, age = 9.0-17.1 years, V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ = 61.6 +/- 7.2 ml/kg/min, and n = 31, age = 8.0-17.7 years, V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ = 46.5 +/- 6.1 ml/kg/min, respectively) and girls (n = 45, age = 8.2-17.0 years, V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ = 51.4 +/- 5.7 ml/kg/min, and n = 36, age = 8.0-17.6 years, V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ = 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 (R-adj(2) = 0.224, P = 0.001) in boys, and Hb mass and interventricular septal thickness (R-adj(2) = 0.317, P = 0.002) in girls partially accounted for the variance in V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$. Post-PHV, stronger predictive models were evident via the inclusion of LV wall thickness and EDV in boys (R-adj(2) = 0.608, P 0.0001), and posterior wall thickness and Hb mass in girls (R-adj(2) = 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 (V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$) 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 V?O2max${\dot{V}_{{{\rm{O}}_{\rm{2}}}{\rm{max}}}}$ before puberty.

ABSTRACT 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.

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.

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.

Dependent on timing of assessment, anesthetic agents and specifically medetomidine negatively affect cardiac function in great apes. The aim of this study was to determine the influence of tiletamine-zolazepam (TZ) with and without medetomidine on cardiac structure and function in healthy chimpanzees (Pan troglodytes) during a period of relative blood pressure stability. Twenty-four chimpanzees living in an African wildlife sanctuary undergoing routine health assessments were stratified by age, sex, and body mass and randomized to be anesthetized using either TZ (6 mg/kg; n = 13; seven males and six females) or a combination of TZ (2 mg/kg) and medetomidine (TZM; 0.02 mg/kg; n = 11; five males and six females). During health checks, regular heart rate and blood pressure readings were taken and a standardized echocardiogram was performed 20-30 min after induction. Data were compared between the two anesthetic groups using independent-samples t or Mann-Whitney U tests. Although heart rate (mean ± SD; TZ: 76 ± 10 bpm; TZM: 65 ± 14 bpm, P = 0.027), cardiac output (TZ: 3.0 ± 0.7 L/min; TZM: 2.4 ± 0.7 L/min, P = 0.032), and mitral A-wave velocities (TZ: 0.51 ± 0.16 cm/s; TZM: 0.36 ± 0.10 cm/s, P = 0.013) were lower in the TZM group, there were no statistically significant differences in cardiac structure or the remaining functional variables between groups. Furthermore, there were no statistical differences in systolic (TZ 114.6 ± 14.9 mmHg; TZM: 123.0 ± 28.1 mmHg; P = 0.289) or diastolic blood pressure (TZ: 81.8 ± 22.3 mmHg, TZM: 83.8 ± 20.1 mmHg; P = 0.827) between the groups during the echocardiogram. This study has shown that during a period of relative blood pressure stability, during the first 20-30 min after induction there are few differences in measures of cardiac structure and function between protocols using TZ with or without medetomidine in healthy chimpanzees.

With each heartbeat, the right ventricle (RV) inputs blood into the pulmonary vascular (PV) compartment, which conducts blood through the lungs at low pressure and concurrently fills the left atrium (LA) for output to the systemic circulation. This overall hemodynamic function of the integrated RV-PV-LA unit is determined by complex interactions between the components that vary over the cardiac cycle but are often assessed in terms of mean pressure and flow. Exercise challenges these hemodynamic interactions as cardiac filling increases, stroke volume augments, and cycle length decreases, with PV pressures ultimately increasing in association with cardiac output. Recent cardiopulmonary exercise hemodynamic studies have enriched the available data from healthy adults, yielded insight into the underlying mechanisms that modify the PV pressure-flow relationship, and better delineated the normal limits of healthy responses to exercise. This review will examine hemodynamic function of the RV-PV-LA unit using the two-element Windkessel model for the pulmonary circulation. It will focus on acute PV and LA responses that accommodate increased RV output during exercise, including PV recruitment and distension and LA reservoir expansion, and the integrated mean pressure-flow response to exercise in healthy adults. Finally, it will consider how these responses may be impacted by age-related remodeling and modified by sex-related cardiopulmonary differences. Studying the determinants and recognizing the normal limits of PV pressure-flow relations during exercise will improve our understanding of cardiopulmonary mechanisms that facilitate or limit exercise.

ABSTRACT Pre-participation screening (PPS), using a 12-lead electrocardiogram (ECG), is recommended to identify athletes at risk of sudden cardiac death (SCD). ECG interpretation criteria have been developed to address the concern arising from high false-positives in athletes. There are limited ECG data in elite female footballers. The aims of this study were to (1) compare the ECG outcomes using three published ECG criteria (European Society of Cardiology [ESC], Seattle, International) in elite female footballers and (2) compare ECG data at three different stages of a competitive season. Eighty-one elite female footballers (21 ± 4 yr) completed a medical assessment, anthropometrics, resting blood pressure and a resting 12-lead ECG. Each 12-lead ECG was interpreted in accordance with (1) ESC; (2) Seattle; (3) International Criteria to determine training-related and non-training-related ECG changes. A subset of thirteen (26 ± 4 yr) footballers had repeated resting ECG tests at three time points across the competitive season. Eighty percent of females had training-related ECG patterns. Sinus bradycardia (65%) and early repolarization (42%) were the most common. Using the ESC Criteria 25% (20/81) of the athletes were considered to have an abnormal ECG, compared to 0% using the Seattle and International Criteria, mainly due to alterations in QT length criteria. There were no clinically significant differences in ECG data across a competitive season. The Seattle and International ECG Criteria significantly reduced the number of ECG false-positives in elite female footballers and the time point of PPS within a competitive season is unlikely to alter the PPS outcomes. Abbreviations: AMSSM: American Medical Society for Sports Medicine; ANOVA: Analysis of Variance; BSA: Body Surface Area; ECG: Electrocardiogram; ESC: European Society of Cardiology; FA: Football Association; FIFA: The Fédération Internationale de Football Association (FIFA); F-MARC: FIFA Medical Assessment and Research Centre; LAE: Left atrial enlargement; LVH: Left ventricular hypertrophy; PPS: Pre-participation screening; SCD: Sudden cardiac death

During pregnancy, assessment of cardiac output (6), a fundamental measure of cardiovascular function, provides important insight into maternal adaptation. However, methods for dynamic 6, measurement require validation. The purpose of this study was to estimate the agreement of 6, measured by echocardiography and Modelflow at rest and during submaximal exercise in non -pregnant (n = 18), pregnant (n = 15, 22-26 weeks gestation) and postpartum women (n = 12, 12-16 weeks post-delivery). Simultaneous measurements of 6, derived from echocardiography [criterion] and Modelflow were obtained at rest and during low moderate intensity (25% and 50% peak power output) cycling exercise and compared using Bland -Altman analysis and limits of agreement. Agreement between echocardiography and Modelflow was poor in nonpregnant, pregnant and postpartum women at rest (mean difference SD: -1.1 3.4; -1.2 2.9; -1.9 3.2 Lmin-1), and this remained evident during exercise. The Modelflow method is not recommended for 6, determination in research involving young, healthy non -pregnant and pregnant women at rest or during dynamic challenge. Previously published 6, data from studies utilising this method should be interpreted with caution.

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.