The effect of heat stress, dehydration and exercise on global left ventricular function and mechanics in healthy humans

This thesis was submitted for the degree of Doctor of Philosophy and awarded by Brunel University.This thesis examined the effect of heat stress, dehydration and exercise on global left ventricular (LV) function and LV twist, untwisting and strain (LV mechanics) in healthy individuals. The primary aim was to identify whether the different haemodynamics induced by heat stress, dehydration and exercise would be associated with alterations in systolic and diastolic LV mechanics as assessed by two-dimensional speckle tracking echocardiography. Study one showed that enhanced systolic and diastolic LV mechanics during progressively increasing heat stress at rest likely compensate in part for a lower venous return, resulting in a maintained stroke volume (SV). In contrast, heat stress during knee-extensor exercise did not significantly increase LV twist, suggesting that exercise attenuates the increase in LV mechanics seen during passive heat stress. Study two revealed that dehydration enhances systolic LV mechanics whilst diastolic mechanics remain unaltered at rest, despite pronounced reductions in preload. The maintenance of systolic and diastolic LV mechanics with dehydration during knee-extensor exercise further suggests that the large decline in SV with dehydration and hyperthermia is caused by peripheral cardiovascular factors and not impaired LV mechanics. During both, heat stress and dehydration, enhanced systolic mechanics were achieved solely by increases in basal rotation. In contrast, the third study demonstrated that when individuals are normothermic and euhydrated, systolic and diastolic basal and apical mechanics increase significantly during incremental exercise to approximately 50% peak power. The subsequent plateau suggests that LV mechanics reach their peak at sub-maximal exercise intensities. Together, the present findings emphasise the importance of acute adjustments in both, basal and apical LV mechanics, during periods of increased cardiovascular demand

Response to Comment on: “The Effect of Preterm Birth on Maximal Aerobic Exercise Capacity and Lung Function in Healthy Adults: A Systematic Review and Meta-Analysis”

[No abstract available

The Effect of Preterm Birth on Maximal Aerobic Exercise Capacity and Lung Function in Healthy Adults: A Systematic Review and Meta-analysis

Background: A negative impact of premature birth on health in adulthood is well established. However, it is not clear whether healthy adults who were born prematurely but have similar physical activity levels compared to adults born at term have a reduced maximal aerobic exercise capacity (maximum oxygen consumption [VO2max]). Objective: We aimed to determine the effect of premature birth on aerobic exercise capacity and lung function in otherwise healthy, physically active individuals. Methods: A broad literature search was conducted in the PubMed database. Search terms included ‘preterm/premature birth’ and ‘aerobic exercise capacity’. Maximal oxygen consumption (mL/kg/min) was the main variable required for inclusion, and amongst those investigations forced expiratory volume in 1 s (FEV1, % predicted) was evaluated as a secondary parameter. For the systematic review, 29 eligible articles were identified. Importantly, for the meta-analysis, only studies which reported similar activity levels between healthy controls and the preterm group/s were included, resulting in 11 articles for the VO2max analysis (total n = 688, n = 333 preterm and n = 355 controls) and six articles for the FEV1 analysis (total n = 296, n = 147 preterm and n = 149 controls). Data were analysed using Review Manager (Review Manager. RevMan version 5.4 software. The Cochrane Collaboration; 2020.). Results: The systematic review highlighted the broad biological impact of premature birth. While the current literature tends to suggest that there may be a negative impact of premature birth on both VO2max and FEV1, several studies did not control for the potential influence of differing physical activity levels between study groups, thus justifying a focused meta-analysis of selected studies. Our meta-analysis strongly suggests that prematurely born humans who are otherwise healthy do have a reduced VO2max (mean difference: − 4.40 [95% confidence interval − 6.02, − 2.78] mL/kg/min, p < 0.00001, test for overall effect: Z = 5.32) and FEV1 (mean difference − 9.22 [95% confidence interval − 13.54, − 4.89] % predicted, p < 0.0001, test for overall effect: Z = 4.18) independent of physical activity levels. Conclusions: Whilst the current literature contains mixed findings on the effects of premature birth on VO2max and FEV1, our focused meta-analysis suggests that even when physical activity levels are similar, there is a clear reduction in VO2max and FEV1 in adults born prematurely. Therefore, future studies should carefully investigate the underlying determinants of the reduced VO2max and FEV1 in humans born preterm, and develop strategies to improve their maximal aerobic capacity and lung function beyond physical activity interventions

Young athletes under pressure?

Regular participation in exercise has long been known to result in cardiovascular adaptation. Historically, the ‘athlete’s heart’ hypothesis has encouraged a dichotomised view of the heart’s adaptation to sport, depending on whether the physical activity was either of isotonic activity (runners and swimmers) resulting in ‘cardiomegaly’ or of isometric effort (wrestlers and shot putters, ie, ‘strength’ athletes) with clear peripheral adaptations and an ‘obvious increase in cardiac size’. Today, the classification of sports according to their physiological demands acknowledges a greater diversity of exposure, depending on the physical activity, with an emphasis on a ‘graded transition’ between the main categories: dynamic, static and impact. Still, our understanding of the determinants of structural and functional cardiovascular adaptation to exercise are limited, and the consequences for health remain a matter of debate

CrossTalk proposal: Blood flow pulsatility in left ventricular assist device patients is essential to maintain normal brain physiology

For the first time in history, some humans live without a palpable pulse (Purohit et al. 2018). This remarkable physiology is the consequence of surgical implantation of a continuous‐flow left ventricular assist device (CF‐LVAD) in patients with end‐stage heart failure. Blood flow produced by CF‐LVADs has a low oscillatory profile in the aorta that results in significantly reduced pulsatility in all arterial compartments (Castagna et al. 2017; Fig. 1). Despite remarkable gains in quality of life and longevity, complications that affect not only morbidity, such as gastrointestinal bleeding, but also mortality, such as strokes, are still prevalent in CF‐LVAD patients. Low pulsatility has been proposed as a major culprit in contributing to these adverse events (Mancini & Colombo, 2015; Goldstein et al. 2018). In this CrossTalk proposal, we present the current arguments in favour of maintaining an appropriate amount of arterial pulsatility, in particular in the cerebral circulation, to lower risk in these patients

“Bionic Women and Men”: The Unique Physiology of Left Ventricular Assist Device Patients – Keep your finger on the pulse!

Across many countries in the world, advanced heart failure patients who are eligible for a heart transplant face the same dilemma: there are not enough donor hearts available for all. The current next-best alternative to a heart transplant is the surgical implantation of a left ventricular assist device (LVAD). Although the purpose of the LVAD is to relieve the overloaded left ventricle of heart failure patients and restore a normal cardiac output, patients have presented with high levels of stroke gastrointestinal bleeding and right-heart failure. One potential reason for this increased risk is the continuous flow of the implanted LVAD. As a result, the majority of LVAD patients do not have a palpable pulse (Purohit et al., 2018), creating a unique arterial biology in these humans (Castagna et al., 2017). Perhaps surprising is the superior health outcome of patients supported with continuous-flow (CF) compared with pulsatile-flow LVADs. In addition, the reduced/absent pulsatility in these CF-LVAD patients (see figure 1.) enables the investigation of unique arterial physiology and cardiovascular regulation, which has already revealed some unexpected observations. For example, continuous-flow patients appear to have a higher sympathetic activity (Cornwell et al., 2015), and suffer complications above a low systolic blood pressure of ~100 mmHg, atypical of non-LVAD populations in whom hypertension (>140 mmHg) is a predictor of stroke (Pinsino et al., 2019). Thus, the medical debate whether continuous flow is truly better for the health of advanced heart failure patients also necessitates a more generic, fundamental discussion into ‘normal’ arterial physiology & health. The comprehensive study investigating the detailed cardiovascular response and adaptations to drastically altered haemodynamics in heart failure, with and without LVAD support, at rest, during physical activity and in combination with cardiovascular acting medication, is essential. This unique area of research presents an opportunity to significantly increase our fundamental physiological understanding of the interaction between cardiac dynamics (volume, force, ejection pattern) and arterial regulation (flow, blood pressure, sympathetic activity, endothelial function, pulsatility). Therefore, the symposium entitled “Bionic women and men – Physiology lessons from implantable cardiac devices” held at the 2019 Annual Meeting of The Physiological Society in Aberdeen, UK, brought together clinicians and scientists from a previous CrossTalk debate (Cornwell et al., 2019; Stöhr et al., 2019) to review the current knowledge of LVAD patients and identify outstanding questions in the field. In total, four presentations were given and each of them have been published as symposium reports in this edition of Experimental Physiology

Echocardiographic Assessment of Myocardial Deformation during Exercise

The human heart is an asymmetrical structure that consists of oblique, circumferential, and transmural fibers, as well as laminae and sheets. Sequential electrical activation of all the muscle fibers ultimately results in a coordinated contraction of the heart muscle also referred to as “deformation.” This is immediately followed by myocardial relaxation, when the preceding deformation is reversed, and the ventricles fill with blood. Given the complexity of these repetitive motions, it is not surprising that there is great diversity in the myocardial deformation between different individuals and between distinct populations. Exercise presents a natural challenge to determine the full capacity of an individual’s heart, and modern imaging technologies allow for the non-invasive assessment of myocardial deformation during exercise. In this chapter, the most relevant anatomical basis for myocardial deformation is summarized and definitions of the most relevant parameters are provided. Then, the general cardiac responses to exercise are highlighted before the current knowledge on myocardial deformation during exercise is discussed. The literature clearly indicates that the echocardiographic evaluation of myocardial deformation during exercise holds great promise for the identification of sub-clinical disease. Future studies should aim to determine the mechanisms of differential expression of myocardial deformation during exercise in health and disease

Unaltered left ventricular mechanics and remodelling after 12 weeks of resistance exercise training – a longitudinal study in men

Previous longitudinal studies suggest that left ventricular (LV) structure is unaltered with resistance exercise training (RT) in young men. However, evidence from aerobic exercise training suggests that early changes in functional LV wall mechanics may occur prior to and independently of changes in LV size, although short-term changes in LV mechanics and structural remodelling in response to RT protocols have not been reported. Therefore, the purpose of this study was to examine the effects of RT on LV mechanics in healthy men performing 2 different time-under-tension protocols. Forty recreationally trained men (age: 23 ± 3 years) were randomized into 12 weeks of whole-body higher-repetition RT (20–25 repetitions/set to failure at ∼30%–50% 1 repetition maximum (1RM); n = 13), lower-repetition RT (8–12 repetitions/set to failure at ∼75%–90% 1RM; n = 13), or an active control period (n = 14). Speckle tracking echocardiography was performed at baseline and following the intervention period. Neither RT program altered standard measures of LV volumes (end-diastolic volume, end-systolic volume, or ejection fraction; P > 0.05) or indices of LV mechanics (total LV twist, untwisting rate, twist-to-shortening ratio, untwisting-to-twist ratio, or longitudinal strain; P > 0.05). This is the first longitudinal study to assess both LV size and mechanics after RT in healthy men, suggesting a maintenance of LV size and twist mechanics despite peripheral muscle adaptations to the training programs. These results provide no evidence for adverse LV structural or functional remodelling in response to RT in young men and support the positive role of RT in the maintenance of optimal cardiovascular function, even with strenuous RT

Systolic and Diastolic Left Ventricular Mechanics during and after Resistance Exercise

PURPOSE: To improve the current understanding of the impact of resistance exercise on the heart, by examining the acute responses of left ventricular (LV) strain, twist and untwisting rate ('LV mechanics'). METHODS: LV echocardiographic images were recorded in systole and diastole before, during and immediately after (7-12 s) double leg press exercise at two intensities (30% and 60% of maximum strength, 1-repetition-maximum, 1RM). Speckle tracking analysis generated LV strain, twist and untwisting rate data. Additionally, beat-by-beat blood pressure was recorded and systemic vascular resistance (SVR) and LV wall stress were calculated. RESULTS: Responses in both exercise trials were statistically similar (P > 0.05). During effort, stroke volume decreased while SVR and LV wall stress increased (P 0.05). Immediately following exercise, systolic LV mechanics returned to baseline levels (P < 0.05) but LV untwisting rate increased significantly (P < 0.05). CONCLUSIONS: A single, acute bout of double leg-press resistance exercise transiently reduces systolic LV mechanics, but increases diastolic mechanics following exercise, suggesting that resistance exercise has a differential impact on systolic and diastolic heart muscle function. The findings may explain why acute resistance exercise has been associated with reduced stroke volume but chronic exercise training may result in increased LV volumes

Regarding High Intensity Interval Training and Left Ventricular Mechanics

The influence of exercise on the mechanical function of the heart has become a topic of considerable interest over recent decades. In a recent issue of Medicine and Science in Sports and Exercise, Huang et al. (2) published a study that investigated the effects of high intensity interval training (HIIT) on echocardiographic-derived indices of left ventricular (LV) mechanical function in young, sedentary but otherwise healthy men. We believe that this study has the potential to further our understanding on how the heart responds to exercise, and it ultimately fits within the current knowledge on exercise-induced cardiac adaptation in health and disease (4). However, given the proposed conclusions, we would appreciate additional details from the authors on the methodology used that may have contributed to some unusual results. Specifically, this letter serves to highlight our concerns regarding the two most notable findings reported in the paper by Huang et al (2), namely 1) the unusually large increase in cardiorespiratory fitness following the HIIT intervention, and 2) the exceptionally low values derived from speckle tracking echocardiography