Chie C. Yoshiga

Brain and central haemodynamics and oxygenation during maximal exercise in humans

During maximal exercise in humans, fatigue is preceded by reductions in systemic and skeletal muscle blood flow, O2 delivery and uptake. Here, we examined whether the uptake of O2 and substrates by the human brain is compromised and whether the fall in stroke volume of the heart underlying the decline in systemic O2 delivery is related to declining venous return. We measured brain and central haemodynamics and oxygenation in healthy males (n= 13 in 2 studies) performing intense cycling exercise (360 ± 10 W; mean ±s.e.m.) to exhaustion starting with either high (H) or normal (control, C) body temperature. Time to exhaustion was shorter in H than in C (5.8 ± 0.2 versus 7.5 ± 0.4 min, P < 0.05), despite heart rate reaching similar maximal values. During the first 90 s of both trials, frontal cortex tissue oxygenation and the arterial–internal jugular venous differences (a‐v diff) for O2 and glucose did not change, whereas middle cerebral artery mean flow velocity (MCA Vmean) and cardiac output increased by ∼22 and ∼115%, respectively. Thereafter, brain extraction of O2, glucose and lactate increased by ∼45, ∼55 and ∼95%, respectively, while frontal cortex tissue oxygenation, MCA Vmean and cardiac output declined ∼40, ∼15 and ∼10%, respectively. At exhaustion in both trials, systemic declined in parallel with a similar fall in stroke volume and central venous pressure; yet the brain uptake of O2, glucose and lactate increased. In conclusion, the reduction in stroke volume, which underlies the fall in systemic O2 delivery and uptake before exhaustion, is partly related to reductions in venous return to the heart. Furthermore, fatigue during maximal exercise, with or without heat stress, in healthy humans is associated with an enhanced rather than impaired brain uptake of O2 and substrates.

Limitations to systemic and locomotor limb muscle oxygen delivery and uptake during maximal exercise in humans.

Reductions in systemic and locomotor limb muscle blood flow and O2 delivery limit aerobic capacity in humans. To examine whether O2 delivery limits both aerobic power and capacity, we first measured systemic haemodynamics, O2 transport and O2 uptake during incremental and constant (372 ± 11 W; 85% of peak power; mean ±s.e.m.) cycling exercise to exhaustion (n= 8) and then measured systemic and leg haemodynamics and during incremental cycling and knee‐extensor exercise in male subjects (n= 10). During incremental cycling, cardiac output and systemic O2 delivery increased linearly to 80% of peak power (r2= 0.998, P < 0.001) and then plateaued in parallel to a decline in stroke volume (SV) and an increase in central venous and mean arterial pressures (P < 0.05). In contrast, heart rate and increased linearly until exhaustion (r2= 0.993; P < 0.001) accompanying a rise in systemic O2 extraction to 84 ± 2%. In the exercising legs, blood flow and O2 delivery levelled off at 73–88% of peak power, blunting leg per unit of work despite increasing O2 extraction. When blood flow increased linearly during one‐legged knee‐extensor exercise, per unit of work was unaltered on fatigue. During constant cycling, , SV, systemic O2 delivery and reached maximal values within ∼5 min, but dropped before exhaustion (P < 0.05) despite increasing or stable central venous and mean arterial pressures. In both types of maximal cycling, the impaired systemic O2 delivery was due to the decline or plateau in because arterial O2 content continued to increase. These results indicate that an inability of the circulatory system to sustain a linear increase in O2 delivery to the locomotor muscles restrains aerobic power. The similar impairment in SV and O2 delivery during incremental and constant load cycling provides evidence for a central limitation to aerobic power and capacity in humans.

Effect of thermal stress on Frank–Starling relations in humans

The Frank–Starling ‘law of the heart’ is implicated in certain types of orthostatic intolerance in humans. Environmental conditions have the capacity to modulate orthostatic tolerance, where heat stress decreases and cooling increases orthostatic tolerance. The objective of this project was to test the hypothesis that heat stress augments and cooling attenuates orthostatic‐induced decreases in stroke volume (SV) via altering the operating position on a Frank–Starling curve. Pulmonary artery catheters were placed in 11 subjects for measures of pulmonary capillary wedge pressure (PCWP) and SV (thermodilution derived cardiac output/heart rate). Subjects experienced lower‐body negative‐pressure (LBNP) of 0, 15 and 30 mmHg during normothermia, skin‐surface cooling (decrease in mean skin temperature of 4.3 ± 0.4°C (mean ±s.e.m.) via perfusing 16°C water through a tubed‐lined suit), and whole‐body heating (increase in blood temperature of 1.0 ± 0.1°C via perfusing 46°C water through the suit). SV was 123 ± 8, 121 ± 10, 131 ± 7 ml prior to LBNP, during normothermia, skin‐surface cooling, and whole‐body heating, respectfully (P= 0.20). LBNP of 30 mmHg induced greater decreases in SV during heating (−48.7 ± 6.7 ml) compared to normothermia (−33.2 ± 7.4 ml) and to cooling (−10.3 ± 2.9 ml; all P < 0.05). Relating PCWP to SV indicated that cooling values were located on the flatter portion of a Frank–Starling curve because of attenuated decreases in SV per decrease in PCWP. In contrast, heating values were located on the steeper portion of a Frank–Starling curve because of augmented decreases in SV per decrease in PCWP. These data suggest that a Frank–Starling mechanism may contribute to improvements in orthostatic tolerance during cold stress and orthostatic intolerance during heat stress.

Effects of heat and cold stress on central vascular pressure relationships during orthostasis in humans

Central venous pressure (CVP) provides information regarding right ventricular filling pressure, but is often assumed to reflect left ventricular filling pressure. It remains unknown whether this assumption is correct during thermal challenges when CVP is elevated during skin‐surface cooling or reduced during whole‐body heating. The primary objective of this study was to test the hypothesis that changes in CVP reflect those in left ventricular filling pressure, as expressed by pulmonary capillary wedge pressure (PCWP), during lower‐body negative pressure (LBNP) while subjects are normothermic, during skin‐surface cooling, and during whole‐body heating. In 11 subjects, skin‐surface cooling was imposed by perfusing 16°C water through a water‐perfused suit worn by each subject, while heat stress was imposed by perfusing 47°C water through the suit sufficient to increase internal temperature 0.95 ± 0.07°C (mean ±s.e.m.). While normothermic, CVP was 6.3 ± 0.2 mmHg and PCWP was 9.5 ± 0.3 mmHg. These pressures increased during skin‐surface cooling (7.8 ± 0.2 and 11.1 ± 0.3 mmHg, respectively; P < 0.05) and decreased during whole‐body heating (3.6 ± 0.1 and 6.5 ± 0.2 mmHg, respectively; P < 0.05). The decrease in CVP with LBNP was correlated with the reduction in PCWP during normothermia (r= 0.93), skin‐surface cooling (r= 0.91), and whole‐body heating (r= 0.81; all P < 0.001). When these three thermal conditions were combined, the overall r value between CVP and PCWP was 0.92. These data suggest that in the assessed thermal conditions, CVP appropriately tracks left ventricular filling pressure as indexed by PCWP. The correlation between these values provides confidence for the use of CVP in studies assessing ventricular preload during thermal and combined thermal and orthostatic perturbations.

Atrial natriuretic peptide and acute changes in central blood volume by hyperthermia in healthy humans

Background Hyperthermia induces vasodilatation that reduces central blood volume (CBV), central venous pressure (CVP) and mean arterial pressure (MAP). Inhibition of atrial natriuretic peptide (ANP) could be a relevant homeostatic defense mechanism during hyperthermia with a decrease in CBV. The present study evaluated how changes in plasma ANP reflect the changes in CBV during hyperthermia. Methods Ten healthy subjects provided with a water perfused body suit increased body core temperature 1 °C. In situ labeled autologous red blood cells were used to measure the CBV with a gamma camera. Regions of interest were traced manually on the images of the whole body blood pool scans. Two measures of CBV were used: Heart/whole body ratio and thorax/whole body ratio. CVP and MAP were recorded. Arterial (ANPart) and venous plasma ANP were determined by radioimmunoassay. Results The ratio thorax/whole body and heart/whole body decreased 7 % and 11 %, respectively (p<0.001). MAP and CVP decreased during hyperthermia by 6.8 and 5.0 mmHg, respectively (p<0.05; p<0.001). Changes in both thorax/whole body (R=0.80; p<0.01) and heart/whole body ratios (R=0.78; p<0.01) were correlated with changes in ANPart. However, there was no correlation between venous ANP and changes in CBV, nor between ANPart and MAP or CVP. Conclusion Arterial but not venous plasma concentration of ANP, is correlated to changes in CBV, but not to pressures. We suggest that plasma ANPart may be used as a surrogate marker of acute CBV changes.

Renal lactate elimination is maintained during moderate exercise in humans

Abstract Reduced hepatic lactate elimination initiates blood lactate accumulation during incremental exercise. In this study, we wished to determine whether renal lactate elimination contributes to the initiation of blood lactate accumulation. The renal arterial-to-venous (a-v) lactate difference was determined in nine men during sodium lactate infusion to enhance the evaluation (0.5 mol · L−1 at 16 ± 1 mL · min−1; mean ± s) both at rest and during cycling exercise (heart rate 139 ± 5 beats · min−1). The renal release of erythropoietin was used to detect kidney tissue ischaemia. At rest, the a-v O2 (CaO2-CvO2) and lactate concentration differences were 0.8 ± 0.2 and 0.02 ± 0.02 mmol · L−1, respectively. During exercise, arterial lactate and CaO2-CvO2 increased to 7.1 ± 1.1 and 2.6 ± 0.8 mmol · L−1, respectively (P < 0.05), indicating a ∼70% reduction of renal blood flow with no significant change in the renal venous erythropoietin concentration (0.8 ± 1.4 U · L−1). The a-v lactate concentration difference increased to 0.5 ± 0.8 mmol · L−1, indicating similar lactate elimination as at rest. In conclusion, a ∼70% reduction in renal blood flow does not provoke critical renal ischaemia, and renal lactate elimination is maintained. Thus, kidney lactate elimination is unlikely to contribute to the initial blood lactate accumulation during progressive exercise.