Circulatory limitations to exercise capacity in humans: the impact of heat stress and dehydration on brain and muscle blood flow and metabolism

This thesis was submitted for the award of Doctor of Philosophy and was awarded by Brunel University LondonHeat stress and dehydration pose a severe challenge to physiological function and the capability to perform physical work. There is, however, limited knowledge on the regional haemodynamic and metabolic responses to strenuous exercise in environmentally stressful conditions. The primary aim of this thesis was to examine whether dehydration and heat stress compromise brain, muscle and systemic blood flow and metabolism, and whether depressed brain and muscle oxygen delivery underpin reduced exercise capacity during graded incremental and prolonged exercise. This thesis makes an original contribution to the knowledge by showing for the first time that dehydration markedly accelerates the decline in cerebral blood flow during maximal incremental (Chapter 4) and prolonged sub-maximal exercise (Chapter 5) in the heat. Cerebral metabolism, however, is preserved by compensatory increases in substrate extraction. Falling carbon dioxide tension underpinned the decline in CBF. However, a distinct regional distribution of blood flow across the head was observed, suggesting that different mechanisms are responsible for the regulation of regional blood flow within the head. A reduced cerebral metabolism is therefore an unlikely factor explaining the compromised exercise capacity in physiologically stressful hot environments. Rather, restrictions in active muscle blood flow and oxygen supply, which are not apparent during sub-maximal exercise, may explain the reduced maximal aerobic power in heat stressed conditions. For the first time we have manipulated skin and core temperature to show that combined internal and skin hyperthermia reduces maximal aerobic power in association with restrictions in limb, brain and systemic blood flow and skeletal muscle metabolism (Chapter 6). Overall, the findings of the present thesis provide novel information on how circulatory limitations across contracting skeletal muscle, brain and systemic tissues and organs might underpin the impairment in exercise capacity in physiologically taxing environments evoking significant dehydration and hyperthermia.Gatorade Sports Science Institute, PepsiCo Inc., US

Whole-body heat stress and exercise stimulate the appearance of platelet microvesicles in plasma with limited influence of vascular shear stress

Intense, large muscle mass exercise increases circulating microvesicles, but our understanding of microvesicle dynamics and mechanisms inducing their release remains limited. However, increased vascular shear stress is generally thought to be involved. Here, we manipulated exercise-independent and exercise-dependent shear stress using systemic heat stress with localized single-leg cooling (low shear) followed by single-leg knee extensor exercise with the cooled or heated leg (Study 1, n = 8) and whole-body passive heat stress followed by cycling (Study 2, n = 8). We quantified femoral artery shear rates (SRs) and arterial and venous platelet microvesicles (PMV-CD41+) and endothelial microvesicles (EMV-CD62E+). In Study 1, mild passive heat stress while one leg remained cooled did not affect [microvesicle] (P ≥ 0.05). Single-leg knee extensor exercise increased active leg SRs by ~12-fold and increased arterial and venous [PMVs] by two- to threefold, even in the nonexercising contralateral leg (P < 0.05). In Study 2, moderate whole-body passive heat stress increased arterial [PMV] compared with baseline (mean±SE, from 19.9 ± 1.5 to 35.5 ± 5.4 PMV.μL-1.103, P < 0.05), and cycling with heat stress increased [PMV] further in the venous circulation (from 27.5 ± 2.2 at baseline to 57.5 ± 7.2 PMV.μL-1.103 during cycling with heat stress, P < 0.05), with a tendency for increased appearance of PMV across exercising limbs. Taken together, these findings demonstrate that whole-body heat stress may increase arterial [PMV], and intense exercise engaging either large or small muscle mass promote PMV formation locally and systemically, with no influence upon [EMV]. Local shear stress, however, does not appear to be the major stimulus modulating PMV formation in healthy humans

Temperature and blood flow distribution in the human leg during passive heat stress

The influence of temperature on the hemodynamic adjustments to direct passive heat stress within the leg’s major arterial and venous vessels and compartments remains unclear. Fifteen healthy young males were tested during exposure to either passive whole-body heat stress to levels approaching thermal tolerance (core temperature, Tc + 2 °C; Study 1; n=8) or single leg heat stress (Tc + 0 °C; Study 2; n=7). Whole-body heat stress increased perfusion and decreased oscillatory shear index in relation to the rise in Tleg in all three major arteries supplying the leg - plateauing in the common and superficial femoral arteries prior to reaching severe heat stress levels. Isolated leg heat stress increased arterial blood flows and shear patterns to a level similar to that obtained during moderate core hyperthermia (Tc + 1°C). Despite modest increases in great saphenous venous blood flow (0.2 l/min), the deep venous system accounted for the majority of returning flow (common femoral vein 0.7l/min) during intense to severe levels of heat stress. Rapid cooling of a single leg during severe whole-body heat stress resulted in an equivalent blood flow reduction in the major artery supplying the thigh deep tissues only - suggesting central temperature-sensitive mechanisms contribute to skin blood flow alone. These findings further our knowledge of leg hemodynamic responses during direct heat stress and provide evidence of potentially beneficial vascular alterations during isolated limb heat stress that are equivalent to those experienced during exposure to moderate levels of whole-body hyperthermia

Clinical Efficacy of Brown Seaweeds Ascophyllum nodosum and Fucus vesiculosus in the Prevention or Delay Progression of the Metabolic Syndrome: A Review of Clinical Trials

Metabolic syndrome (MetS) is a global public health problem affecting nearly 25.9% of the world population characterised by a cluster of disorders dominated by abdominal obesity, high blood pressure, high fasting plasma glucose, hypertriacylglycerolaemia and low HDL-cholesterol. In recent years, marine organisms, especially seaweeds, have been highlighted as potential natural sources of bioactive compounds and useful metabolites, with many biological and physiological activities to be used in functional foods or in human nutraceuticals for the management of MetS and related disorders. Of the three groups of seaweeds, brown seaweeds are known to contain more bioactive components than either red and green seaweeds. Among the different brown seaweed species, Ascophyllum nodosum and Fucus vesiculosus have the highest antioxidant values and highest total phenolic content. However, the evidence base relies mainly on cell line and small animal models, with few studies to date involving humans. This review intends to provide an overview of the potential of brown seaweed extracts Ascophyllum nodosum and Fucus vesiculosus for the management and prevention of MetS and related conditions, based on the available evidence obtained from clinical trials

Dehydration accelerates reductions in cerebral blood flow during prolonged exercise in the heat without compromising brain metabolism

Dehydration hastens the decline in cerebral blood flow (CBF) during incremental exercise, while the cerebral metabolic rate for oxygen (CMRO2) is preserved. It remains unknown whether CMRO2 is also maintained during prolonged exercise in the heat and whether an eventual decline in CBF is coupled to fatigue. Two studies were undertaken. In study 1, ten male cyclists cycled in the heat for ~2 h with (control) and without fluid replacement (dehydration) while internal (ICA) and external (ECA) carotid artery blood flow and core and blood temperature were obtained. Arterial and internal jugular venous blood samples were assessed with dehydration to evaluate the CMRO2. In study 2 (8 males), middle cerebral artery blood velocity (MCA Vmean) was measured during prolonged exercise to exhaustion in both dehydrated and euhydrated states. After a rise at the onset of exercise, ICA flow declined to baseline with progressive dehydration (P < 0.05). However, cerebral metabolism remained stable through enhanced oxygen and glucose extraction (P < 0.05). ECA flow increased for one hour but declined prior to exhaustion. Fluid ingestion maintained cerebral and extra-cranial perfusion throughout non-fatiguing exercise. During exhaustive exercise, however, euhydration delayed but did not prevent the decline in cerebral perfusion. In conclusion, during prolonged exercise in the heat dehydration accelerates the decline in CBF without affecting CMRO2 and also restricts extra-cranial perfusion. Thus fatigue is related to reduction in CBF and extra-cranial perfusion rather than in CMRO2.The study was supported by a grant from the Gatorade Sports Science Institute, PepsiCo Inc, USA

Conclusions of the II International and IV Spanish Hydration Congress. Toledo, Spain, 2nd-4th December, 2015

Water is the major component of our organism representing about 60% of total body weight in adults and has to be obtained through the consumption of different foods and beverages as part of our diet. Water is an essential nutrient performing important functions, including transport of other nutrients, elimination of waste products, temperature regulation, lubrication and structural support. In this context, hydration through water has an essential role in health and wellness, which has been highly acknowledged in recent years among the health community experts such as nutritionists, dietitians, general practitioners, pharmacists, educators, as well as by physical activity and sport sciences experts and the general population