Books

The physiology of aerobic capacity in women
Author: David Montero. Editorial: Routledge, Taylor & Francis Group.
1st edition: 20.12.2024. ISBN: 9781032776934.

Selected Publications

1. Guo M, Liu X, Dixon S, Tse HF, Montero D. Effects of angiotensin II receptor type 1 blockade combined with endurance training on hemoglobin mass and aerobic capacity: a randomized placebo-controlled trial. Cardiovascular Research 2025.
2. Gunawardana D, Guo M, Montero D. Lean body mass associates with a hypertensive cardiovascular phenotype in men but not in women. J Cachexia Sarcopenia Muscle 2025.
3. Meihan Guo, Montero D. Did you know? Does calcium supplementation negate erythropoiesis with endurance training? Acta Physiol 2025.
4. Guo M, Montero D. Medium-Term Effects of Increased Water Intake and Head-Up Sleep on Cardiovascular Health. JACC Adv 2024.
5. Guo M, Montero D. Hans Chinese consume less O2 for muscular work than European-American. Mil Med Res 2024.
6. Guo M, Montero D. Did you know? Is there a reserve in myocardial work via the Frank-Starling mechanism in healthy humans? Acta Physiol 2024.
7. Guo M, Montero D. Women consume less oxygen than men for muscular work: role of lean body mass. Mayo Clinic Proc 2024.
8. Montero D. The carotid baroreflex: the ultimate hemodynamic factor limiting aerobic capacity? J Physiol 2024.
9. Guo M, Diaz-Canestro C, Montero D. The Frank-Starling mechanism is not enough: blood volume expansion prominently decreases pulmonary O2 uptake. Mil Med Res 2024.
10. Guo M, Diaz-Canestro C, Pugliese NR, Paneni F, Montero D. Lean Body Mass and the Cardiorespiratory Phenotype: an Ethnic-Specific Relationship in Hans Chinese Women and Men. J Cachexia Sarcopenia Muscle 2024.
11. Diaz-Canestro C, Tse HF, Yiu KH, Montero D. Reduced lean body mass: a potential modifiable contributor to the pathophysiology of heart failure. Eur Heart J 2023.
12. Meihan Guo, Candela Diaz-Canestro, Ming Ng, Kai Hang Yiu, Montero D. The Chinese cardiorespiratory and circulatory system at work in women and men: a case-control study. Lancet Reg Health West Pac 2023.
13. Guo M, Diaz-Canestro C, Montero D. Blood volume explains the relationship of lean body mass with the cardiovascular system in men but not in women. Mayo Clinic Proc 2023.
14. Diaz-Canestro C, Pentz B, Sehgal A, Yang R, Xu A, Montero D. Lean body mass and the cardiovascular system constitute a female-specific relationship. Sci Transl Med 2022.
15. Diaz-Canestro C, Pentz B, Sehgal A, Montero D. Sex differences in cardiorespiratory fitness are explained by blood volume and oxygen carrying capacity. Cardiovasc Res. 2021.
16. Diaz-Canestro C, Montero D. Blood volume primarily determines orthostatic tolerance in women. J Intern Med 2021.
17. Diaz-Canestro C, Siebenmann C, Montero D. Blood oxygen carrying capacity determines cardiorespiratory fitness in middle-aged and older women and men. Med Sci Sports Exerc 2021.
18. Diaz-Canestro C, Sehgal A, Pentz B, Montero D. Sex specificity in orthostatic tolerance: the integration of hematological, cardiac and endocrine factors. Eur J Prev Cardiol 2021.
19. Diaz-Canestro C, Pentz B, Sehgal A, Montero D. Sex dimorphism in cardiac and aerobic capacities: the influence of body composition. Obesity 2021.
20. Diaz-Canestro C, Montero D. Unveiling women's powerhouse. Exp Physiol 2020.
21. Montero D, Diaz-Canestro C, Oberholzer L, Lundby C. The role of blood volume in cardiac dysfunction and reduced exercise tolerance in patients with diabetes mellitus. Lancet Diabetes Endocrinol 2019.
22. Lundby C, Montero D. Did you know - why does maximal oxygen uptake increase in humans following endurance exercise training? Acta Physiol (Oxf) 2019.
23. Diaz-Canestro C, Montero D. Sex dimorphism of VO2max trainability: a systematic review and meta-analysis. Sports Medicine 2019.
24. Montero D, Diaz-Canestro C. Body height is inversely associated with left ventricular end-diastolic pressure in heart failure with preserved ejection fraction. Eur J Prev Cardiol 2019.
25. Montero D, Lundby, C. Arterial O2 content regulates plasma erythropoietin independently of arterial O2 tension: a blinded crossover study. Kidney Int 2018.
26. Montero D, Lundby, C. Regulation of red blood cell volume with exercise training. Compr Physiol 2018.
27. Montero D, Madsen K, Meinild-Lundby AK, Edin F, Lundby C. Sex dimorphism of substrate utilization: differences in skeletal muscle mitochondrial volume density and function. Exp Physiol 2018.
28. Montero D, Breenfeldt-Andersen A, Oberholzer L, Haider T, Goetze JP, Meinild-Lundby AK, Lundby C. Erythropoiesis with endurance training: dynamics and mechanisms. Am J Physiol Regul Integr Comp 2017.
29. Montero D, Lundby C, Ruschitzka F, Flammer A. True anemia ―red blood cell volume deficit― in heart failure: a systematic review. Circ Heart Fail 2017.
30. Montero D, Flammer A. Exercise intolerance in heart failure with preserved ejection fraction: time to scrutinize diuretic therapy? Eur J Heart Fail 2017.
31. Montero D, Lundby C. Refuting the myth of non-response to exercise training: ‘non-responders’ do respond to higher dose of training. J Physiol 2016.
32. Montero D, Houben AJ, Koster A, Muris DM, Schram MT, Gronenschild EH, Sep SJ, Henry RM, van der Kallen CJ, Schaper NC, Dagnelie PC, van Geel TA, Kremers SP, Savelberg HH, Stehouwer CD. Physical activity is associated with glucose tolerance independent of microvascular function: the Maastricht Study. JCEM 2016.
33. Montero D, Rauber S, Goetze JP, Lundby C. Reduction in central venous pressure enhances erythropoietin synthesis: role of volume-regulating hormones. Acta Physiol (Oxf) 2016.
34. Montero D, Diaz-Cañestro C, Keiser S, Lundby C. Arterial stiffness is strongly and negatively associated with the total volume of red blood cells. Int J Cardiol 2016 June 27.
35. Montero D, Cathomen A, Jacobs RA, Flück D, Leur J, Keiser S, Bonne T, Kirk N, Lundby AK, Lundby C. Haematological rather than skeletal muscle adaptations contribute to the increase in peak oxygen uptake induced by moderate endurance training. J Physiol 2015.
36. Montero D, Diaz-Cañestro, C. Endurance training and VO2max with ageing: role of maximal cardiac output and oxygen extraction. Eur J Prev Cardiol 2015.

What limits maximal O2 consumption (one of the strongest predictors of life expectancy) in humans: the capacity to deliver O2 to the tissues or to extract O2 from the circulation?
The capacity to deliver O2 to the tissues via the circulation is the limiting factor. The capacity to extract O2 by the tissues from the circulation is in excess in humans.

What must be specifically modified in the human body to increase its maximal O2 consumption?
Two variables must be increased: 1) blood volume,¹ specifically the total volume of red blood cells in the circulation, and 2) maximal cardiac output,² which combined with the hemoglobin inside red blood cells determine how much oxygen can be delivered to the tissues.

¹Increased blood volume is not required under unusual hemodynamic stimuli (e.g., supine cycling exercise training).
²Increased maximal cardiac output is not required when the concentration of hemoglobin in blood is increased and blood volume is not reduced. In highly deconditioned individuals, minor increases in maximal O2 consumption may be achieved via a more efficient distribution of cardiac output.

Does blood volume expansion, in isolation, proportionally increase maximal cardiac output?
No, blood volume expansion increases the filling of the heart, but additional adaptations are needed to fully enhance maximal cardiac output in proportion to blood volume.

Do humans have a reserve in cardiac (myocardial) work at maximal exercise?
No, they do not. Artificially increasing the main physiological determinant of myocardial working capacity, i.e., cardiac filling, does not immediately enhance myocardial work at maximal exercise in healthy women and men.

Are there healthy humans that cannot improve their maximal O2 consumption with exercise training?
No, the concept of ‘non-responders’ is a myth. The dose (intensity × duration) of exercise (endurance) training mainly determines the magnitude of improvement in maximal O2 consumption.

Why maximal O2 consumption is higher in men than women matched by the dose of endurance training?
The constitutionally higher blood volume and hemoglobin concentration in men compared with women explain men’s higher maximal O2 consumption.

Does low lean body mass limits cardiac and aerobic capacities in women and men?
In women, lean body mass, whose main component is skeletal muscle, strongly and positively associates with maximal cardiac output and maximal O2 consumption. This suggests that lean body mass is a limiting factor of cardiac and aerobic capacities in women. In men, specifically Caucasians with large body size, lean body mass is NOT associated with cardiac and aerobic capacities. In men with similar lean body mass as women (i.e., small men), lean body mass associates with cardiac and aerobic capacities. Moreover, in women and men with similar lean body mass, most variables reflecting circulatory structure and function, cardiac and aerobic capacities are rather similar.

Is the relationship of lean body mass with cardiac and aerobic capacities explained by blood volume?
No, in women the relationship of lean body mass with cardiac and aerobic capacities is independent of blood volume. In small men (low lean body mass), blood volume MEDIATES the relationship of lean body mass with cardiac and aerobic capacities.

Why women have lower orthostatic tolerance (i.e., the capacity to endure the upright posture) than men?
Because women have a decreased blood volume per unit of body mass compared with men. This is the main primary factor explaining the diminished orthostatic tolerance in women. Reduced blood volume leads to lower filling of the heart and reduced cardiac reserve to pump blood.

Why women consume more fat than men during exercise?
Women have more mitochondria and capacity for fat oxidation in their smaller muscle fibers than men, even when both sexes are matched by maximal O2 consumption and endurance performance. Therefore, women have, in theory, greater metabolic potential for prolonged (>4 hr) efforts, in which metabolic capacities and specifically fat catabolism must be the main energy source.

Is the energetic cost of exercise different between women and men?
Yes, women need less O2 (surrogate of energy cost) than men for a given cycling power output. Such a higher exercise efficiency in women is partly explained by their reduced highly metabolically active mass (i.e., lean body mass) compared with men.

Is the energetic cost of exercise different between Chinese and Caucasian individuals?
Yes, Chinese women and men consume less O2 than Caucasian counterparts for a given cycling power output. The higher exercise efficiency of Chinese is to a minor extent explained by their lower lean body mass compared with Caucasian.

What physiological determinant of endurance exercise capacity differs between Chinese and Caucasian individuals?
The body fat percentage of Chinese women and men is higher than that of Caucasians matched by sex, age and physical activity. Chinese women have lower concentration of hemoglobin in blood, therefore they have less O2 in blood, which reduces their maximal O2 consumption compared with Caucasian women.

Do humans drink enough water?
The typical water intake of women and men is suboptimal (<70 % of optimal water intake). Increased water intake increases cardiac size and improves cardiac function.

Does high blood volume lead to high blood pressure in humans?
No, against the long-standing notion in the medical field, the more blood volume per unit of body mass the lower the blood pressure, independently of maximal O2 consumption, in the vast majority of healthy and diseased women and men.

Is heart failure necessarily associated with blood volume expansion, thus requiring diuretics?
No, blood volume is frequently not increased in heart failure patients, notably in those with preserved ejection fraction.

Does plasma volume confound the concentration of essential blood constituents in heart failure patients?
Yes, the blood concentration of routine markers of anemia and electrolyte balance are linearly associated with the volume of plasma in heart failure patients. Excess or deficit of plasma volume thus confound clinical diagnosis in this population.

Does hemodialysis cause large alterations in blood protein concentration?
Yes, one-third of total circulating albumin (comprising ⁓50 % of proteins in blood) is lost in every liter of plasma volume removed in a hemodialysis session. Low albumin concentration in blood is strongly associated with mortality in hemodialysis patients.

Does high filling pressure remodel the heart of women and men similarly?
No, the internal size of the left ventricle, i.e., the chamber that pumps blood to the body, is decreased in women and increased in men in response to long-term high filling pressure, leading to a more deleterious cardiac remodeling in women. In addition, the lower the body height the higher the left ventricular filling pressure.

Does common antihypertensive medications blocking the renin-angiotensin system compromise adaptations to exercise training?
Yes, even moderate doses of antihypertensive drugs that block the angiotensin type 1 receptor, reduce the amount of hemoglobin in blood and negate the improvement of maximal O2 consumption with endurance training in women. Higher doses of these antihypertensive drugs might similarly affect men.

Seeking PhD candidates, Research Assistants and Postdoctoral Fellows

We are looking for intrinsically motivated students willing to excel in their PhD or postdoctoral research in the fields of Integrative Physiology and Pathophysiology. Candidates from diverse backgrounds are welcomed to apply. Interested candidates please email Dr Montero (dvmb@hku.hk) with your CV, transcripts, and publications (if any) for consideration.