A single 500-mg intravenous iron injection is effective for improving iron status for at least 4 wk, but this does not lead to improved aerobic capacity. This investigation suggests that iron availability supersedes inflammation in the regulation of hepcidin in IDNA endurance athletes after acute intravascular iron injection treatment.

In practice, clinicians generally consider anemia (circulating hemoglobin concentration < 120 g.l−1 in non-pregnant females and < 130 g.l−1 in males) as due to impaired hemoglobin synthesis or increased erythrocyte loss or destruction. Rarely is a rise in plasma volume relative to circulating total hemoglobin mass considered as a cause. But does this matter? We explored this issue in patients, measuring hemoglobin concentration, total hemoglobin mass (optimized carbon monoxide rebreathing method) and thereby calculating plasma volume in healthy volunteers, surgical patients, and those with inflammatory bowel disease, chronic liver disease or heart failure. We studied 109 participants. Hemoglobin mass correlated well with its concentration in the healthy, surgical and inflammatory bowel disease groups (r=0.687–0.871, P<0.001). However, they were poorly related in liver disease (r=0.410, P=0.11) and heart failure patients (r=0.312, P=0.16). Here, hemoglobin mass explained little of the variance in its concentration (adjusted R2=0.109 and 0.052; P=0.11 and 0.16), whilst plasma volume did (R2 change 0.724 and 0.805 in heart and liver disease respectively, P<0.0001). Exemplar patients with identical (normal or raised) total hemoglobin masses were diagnosed as profoundly anemic (or not) depending on differences in plasma volume that had not been measured or even considered as a cause. The traditional inference that anemia generally reflects hemoglobin deficiency may be misleading, potentially resulting in inappropriate tests and therapeutic interventions to address ‘hemoglobin deficiency’ not ‘plasma volume excess’. Measurement of total hemoglobin mass and plasma volume is now simple, cheap and safe, and its more routine use is advocated.

The ability of the cardiorespiratory system (heart, lungs, blood) to deliver oxygen to exercising skeletal muscle constrains maximum oxygen consumption )(normalVtrue˙O2max, with cardiac output and the concentration of oxygen-carrying haemoglobin ([Hb]) being key limiting parameters. Total blood volume (BV) is the sum of the plasma volume (PV) and the total red cell volume. The measured [Hb] is dependent upon the total circulating mass of haemoglobin (tHb-mass) and plasma volume (PV). While the proportion of oxygen carried in plasma is trivial (0.3 mL of oxygen per 100 mL of plasma), each gram of Hb, contained in red blood cells, binds 1.39 mL of oxygen. As a result, the relationship between trueV˙normalO2max and tHb-mass is stronger than that observed between trueV˙normalO2max and [Hb] or BV. The glycoprotein hormone erythropoietin drives red cell synthesis and, like simple transfusion of packed red blood cells, can increase tHb-mass. An iron-containing haem group lies at the centre of the Hb molecule and, in situations of actual or functional iron deficiency, tHb-mass will also rise following iron administration. However achieved, an increase in tHb-mass also increases circulating oxygen-carrying capacity, and thus the capacity for aerobic phosphorylation. It is for such reasons that alterations in trueV˙normalO2max and exercise performance are proportional to those in arterial oxygen content and systemic oxygen transport, a change in tHb-mass of 1 g being associated with a 4 mL · min−1 change in trueV˙normalO2max. Similarly, trueV˙normalO2max increases by approximately 1% for each 3 g · L−1 increase in [Hb] over the [Hb] range (120 to 170 g · L−1). Surgery, like exercise, places substantial metabolic demands on the patient. Whilst subject to debate, oxygen supply at a rate inadequate to prevent muscle anaerobiosis may underpin the occurrence of the anaerobic threshold (AT), an important submaximal marker of cardiorespiratory fitness. Preoperatively, cardiopulmonary exercise testing (CPET) can be used to determine AT and peak exertional oxygen uptake (trueV˙normalO2 peak) as measures of ability to meet increasing oxygen demands. The degree of surgical insult and the ability to meet the resulting additional postoperative oxygen demand appear to be fundamental determinants of surgical outcome: individuals in whom such ability is impaired (and thus those with reduced trueV˙normalO2 peak and AT) are at greater risk of adverse surgical outcome. This review provides an overview of the relationships between [Hb], tHb-mass, exercise capacity, and surgical outcome and discusses the potential value of assessing tHb-mass over [Hb].

Exercise-induced cardiac remodeling (EICR) and the attendant myocardial adaptations characteristic of the athlete's heart may regress during periods of exercise reduction or abstinence. The time course and mechanisms underlying this reverse remodeling, specifically the impact of concomitant plasma volume (PV) contraction on cardiac chamber size, remain incompletely understood. We therefore studied recreational runners ( n = 21, age 34 ± 7 yr; 48% male) who completed an 18-wk training program (~7 h/wk) culminating in the 2016 Boston Marathon after which total exercise exposure was confined to <2 h/wk (no single session >1 h) for 8 wk. Cardiac structure and function, exercise capacity, and PV were assessed at peak fitness (10-14 days before) and at 4 wk and 8 wk postmarathon. Mixed linear modeling adjusting for age, sex, V̇o, and marathon finish time was used to compare data across time points. Physiological detraining was evidenced by serial reductions in treadmill performance. Two distinct phases of myocardial remodeling and hematological adaptation were observed. After 4 wk of detraining, there were significant reductions in PV (Δ -6.0%, P < 0.01), left ventricular (LV) wall thickness (Δ -8.1%, <0.05), LV mass (Δ -10.3%, P < 0.001), and right atrial area (Δ -8.2%, P < 0.001). After 8 wk of detraining, there was a significant reduction in right ventricle chamber size (end-diastolic area Δ = -8.0%, P < 0.05) without further concomitant reductions in PV or LV wall thickness. Abrupt reductions in exercise training stimulus result in a structure-specific time course of reverse cardiac remodeling that occurs largely independently of PV contraction. NEW & NOTEWORTHY Significant reverse cardiac remodeling, previously documented among competitive athletes, extends to recreational runners and occurs with a distinct time course. Initial reductions in plasma volume and left ventricular (LV) mass, driven by reductions in wall thickness, are followed by contraction of the right ventricle. Consistent with data from competitive athletes, LV chamber volumes appear less responsive to detraining and may be a more permanent adaptation to sport.

In contrast to [Hb], tHb-mass is an important determinant of physical fitness before major elective surgery. Further studies should determine whether low tHb-mass is predictive of poor outcome and whether targeted increases in tHb-mass might thus improve outcome.