Hyperthermia‐induced changes in blood flow dynamics and their influence on cardiac output

Our understanding of cardiovascular haemodynamics and the factors that govern it is vital for appreciating the workings of a healthy physiological system, as well as elucidating the pathophysiology behind disease and identifying potential treatment options. A recent article in The Journal of Physiology by Watanabe et al. (2024) sought to contribute to this field by exploring the impact of passive hyperthermia on human circulation and the underlying central and peripheral mechanisms. It has traditionally been believed that blood circulation is driven by the pressure created by the heart (Furst & González-Alonso, 2023). In hyperthermia, cardiac output is increased, and the traditional perspective would suggest that this is mainly due to an increased heart rate, supplemented by central mechanisms such as increased left ventricular systolic function. However, studies have shown that an increased heart rate alone is not sufficient to increase cardiac output (Joyce & Wang, 2021). Also, central mechanisms exert their effects with increases in core temperature at rest, which would not explain the increase in cardiac output seen with peripheral hyperthermia that does not affect core temperature. Therefore, it appears that other factors are involved in increasing cardiac output in peripheral hyperthermia, potentially including increased blood velocity or increased systemic vascular conductance. The exact mechanisms and their relationship to central forces are not well elucidated, and this is what Watanabe et al. (2024) set out to understand. The main aim set by Watanabe et al. (2024) was to explore how single-leg, two-leg, and whole-body hyperthermia affect peripheral and systemic circulation, as well as the metabolic and cardiorespiratory responses. They also aimed to investigate the factors affecting central haemodynamic changes in hyperthermia. Their hypothesis was that passive hyperthermia increases cardiac output, not due to central mechanisms like left ventricular contractility, but rather due to peripheral haemodynamic changes. The researchers enrolled eight young healthy males, and each participant was randomly assigned four counterbalanced protocols. These were 3 h of no heating as a control, 3 h of single-leg heating, 3 h of two-leg heating and 2.5 h of whole-body heating. The latter is shorter due to participant discomfort leading to early termination. The heating was provided using a water-perfused garment, and extensive measurements were taken throughout the protocols. To evaluate leg, arm, and head haemodynamics, ultrasound was used to measure blood flow at the common femoral artery, brachial artery, and common and internal carotid arteries. To evaluate cardiac function, echocardiography was used. Participants also underwent blood sampling, as well as respiratory, metabolic, blood pressure, and heart rate measurements. In single-leg heating, the study found that blood flow only increased in the leg. The two-leg and whole-body heating protocols, however, showed increased blood flow to both legs and forearms, with whole-body heating also leading to increased extracranial blood flow. None of the heating trials showed a significant difference in anterior cerebral blood flow. This finding is particularly interesting given the progressive increase in cardiac output across protocols. These results suggest that local mechanisms controlling blood flow differ across body sites, and that increased cardiac output alone does not increase perfusion. Importantly, the authors found that blood velocity increased to a greater extent than vessel diameter size, indicating that velocity predominantly contributed to the observed increase in blood flow. Additionally, there was a progressive increase in systemic vascular conductance across all heating protocols, along with increased blood kinetic energy in both two-leg and whole-body heating. Using correlational analysis, the authors showcased that increased local temperature was associated with increased local blood flow and vascular conductance. Further analysis suggests that increased cardiac output is linked with not only the aforementioned factors but also increased blood velocity and kinetic energy in the limbs and head. This supports the study's hypothesis and highlights that peripheral mechanisms may be more important than previously thought. Evaluating cardiac function revealed some key findings. Left ventricular ejection fraction and heart rate increased in all heating sessions. However, alongside the increase in heart rate was a reduction in left ventricular filling and ejection times. Despite this, stroke volume was increased or maintained in all heating protocols. This finding is likely to be due to an increase in venous return to the heart, with an increase in left ventricular end diastolic volume and a reduction in the end systolic volume. Collectively, these results indicate that hyperthermia not only drives heart rate but crucially increases venous return to enhance cardiac output. This goes against existing literature, which suggests hyperthermia reduces preload (Wilson & Crandall, 2011), possibly due to factors such as the method of assessing preload, environmental conditions, and participant characteristics. Further research would help to confirm this result. A unique finding was that whole-body heating increased left ventricular twist and untwisting rate, an effect not seen with leg-only heating. This suggests that systemic hyperthermia may engage more comprehensive cardiac adjustments, and that peripheral heating increases cardiac output without necessarily relying on central cardiac mechanisms. These findings come together to suggest an alternative model of circulation, contrary to the traditional cardio-centric view. The study found that respiratory and metabolic responses only changed in the whole-body heating protocol. There was an increase in oxygen uptake, carbon dioxide output, pulmonary ventilation, and end-tidal O2 pressure. In contrast, these changes were not observed in leg-only heating, yet cardiac output still increased. This differentiation suggests that metabolic and respiratory factors are not essential for increasing blood flow in peripheral hyperthermia, thereby strengthening the hypothesis of the study. However, it also shows the ongoing role of central mechanisms in certain hyperthermia conditions. This study is thoughtfully planned and provides robust data supporting the hypothesis. However, it should be noted that there are some limitations. One such limitation is the small and specific sample size of young healthy males. Although this is understandable in the context of an initial study exploring physiology in a normal state, it does reduce the generalisability of the results to other populations such as females and older groups with cardiovascular illness. Additionally, many measurements were derived using ultrasound, which tends to have a degree of inter-operator variability. It is unclear whether one or more operators were involved in conducting these measurements. However, the authors provide a thorough explanation of the ultrasound techniques used. Furthermore, the study did not directly measure right heart function or venous flow to the heart, instead inferring venous return data from their left ventricular recordings. Although this may lead to inaccuracies, similar techniques have been previously used and support this method. The authors also acknowledged that they used correlational analysis to evaluate the link between cardiac output and peripheral circulation, appropriately highlighting that this does not establish causation. The authors provide us with new insights into how human circulation is controlled, in a field where specific mechanisms behind heat-related changes are not well understood. With a deeper understanding of peripheral haemodynamics and the relationship with cardiac output, we are better positioned to conduct future research and explore treatment options for cardiovascular disease. For example, one can evaluate these findings in the context of heart failure and the potential use of lower limb heating to improve cardiac output. Although this has been previously studied (Inoue et al., 2012), there is a dearth of literature. Another interesting possibility is the use of the measurements from this study, such as blood kinetic energy, as markers of disease onset and progression, given their suggested importance. This is an important study from Watanabe et al. (2024), employing a well thought out methodology to suggest that peripheral mechanisms in passive hyperthermia are key to controlling blood circulation. They demonstrate that increases in cardiac output are linked with increases in local velocity and kinetic energy of blood flow secondary to heat, rather than central mechanisms. While there are some limitations to the research, the findings provide new insights into the study of human circulation and establish a platform for further research. This should include further physiological research in diverse populations to confirm the results, as well as clinical research to understand changes found in pathology and to identify possible treatment options. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. No competing interests declared. Sole author. None.