Transcriptomic Markers of Recombinant Human Erythropoietin Micro-Dosing in Thoroughbred Horses

Recombinant human erythropoietin (rHuEPO) is a well-known performance enhancing drug in human athletes, and there is anecdotal evidence of it being used in horse racing for the same purpose. rHuEPO, like endogenous EPO, increases arterial oxygen content and thus aerobic power. Micro-doping, or injecting smaller doses over a longer period of time, has become an important concern in both human and equine athletics since it is more difficult to detect. Horses offer an additional challenge of a contractile spleen, thus large changes in the red blood cell mass occur naturally. To address the challenge of detecting rHuEPO doping in horse racing, we determined the transcriptomic effects of rHuEPO micro-dosing over seven weeks in exercised Thoroughbreds. RNA-sequencing of peripheral blood mononuclear cells isolated at several time points throughout the study identified three transcripts (C13H16orf54, PUM2 and CHTOP) that were significantly (PFDR < 0.05) different between the treatment groups across two or three time point comparisons. PUM2 and CHTOP play a role in erythropoiesis while not much is known about C13H16orf54, but it is primarily expressed in whole blood. However, gene expression differences were not large enough to detect via RT-qPCR, thereby precluding their utility as biomarkers of micro-doping.

Effect of Exercise-Induced Reductions in Blood Volume on Cardiac Output and Oxygen Transport Capacity

We wanted to demonstrate the relationship between blood volume, cardiac size, cardiac output and maximum oxygen uptake (V.O2max) and to quantify blood volume shifts during exercise and their impact on oxygen transport. Twenty-four healthy, non-smoking, heterogeneously trained male participants (27 ± 4.6 years) performed incremental cycle ergometer tests to determine V.O2max and changes in blood volume and cardiac output. Cardiac output was determined by an inert gas rebreathing procedure. Heart dimensions were determined by 3D echocardiography. Blood volume and hemoglobin mass were determined by using the optimized CO-rebreathing method. The V.O2max ranged between 47.5 and 74.1 mL⋅kg–1⋅min–1. Heart volume ranged between 7.7 and 17.9 mL⋅kg–1 and maximum cardiac output ranged between 252 and 434 mL⋅kg–1⋅min–1. The mean blood volume decreased by 8% (567 ± 187 mL, p = 0.001) until maximum exercise, leading to an increase in [Hb] by 1.3 ± 0.4 g⋅dL–1 while peripheral oxygen saturation decreased by 6.1 ± 2.4%. There were close correlations between resting blood volume and heart volume (r = 0.73, p = 0.002), maximum blood volume and maximum cardiac output (r = 0.68, p = 0.001), and maximum cardiac output and V.O2max (r = 0.76, p &lt; 0.001). An increase in maximum blood volume by 1,000 mL was associated with an increase in maximum stroke volume by 25 mL and in maximum cardiac output by 3.5 L⋅min–1. In conclusion, blood volume markedly decreased until maximal exhaustion, potentially affecting the stroke volume response during exercise. Simultaneously, hemoconcentrations maintained the arterial oxygen content and compensated for the potential loss in maximum cardiac output. Therefore, a large blood volume at rest is an important factor for achieving a high cardiac output during exercise and blood volume shifts compensate for the decrease in peripheral oxygen saturation, thereby maintaining a high arteriovenous oxygen difference.

Transcranial Doppler in Acute COVID-19 Infection

Background and Purpose: Stroke may complicate coronavirus disease 2019 (COVID-19) infection based on clinical hypercoagulability. We investigated whether transcranial Doppler ultrasound has utility for identifying microemboli and clinically relevant cerebral blood flow velocities (CBFVs) in COVID-19. Methods: We performed transcranial Doppler for a consecutive series of patients with confirmed or suspected COVID-19 infection admitted to 2 intensive care units at a large academic center including evaluation for microembolic signals. Variables specific to hypercoagulability and blood flow including transthoracic echocardiography were analyzed as a part of routine care. Results: Twenty-six patients were included in this analysis, 16 with confirmed COVID-19 infection. Of those, 2 had acute ischemic stroke secondary to large vessel occlusion. Ten non-COVID stroke patients were included for comparison. Two COVID-negative patients had severe acute respiratory distress syndrome and stroke due to large vessel occlusion. In patients with COVID-19, relatively low CBFVs were observed diffusely at median hospital day 4 (interquartile range, 3–9) despite low hematocrit (29.5% [25.7%–31.6%]); CBFVs in comparable COVID-negative stroke patients were significantly higher compared with COVID-positive stroke patients. Microembolic signals were not detected in any patient. Median left ventricular ejection fraction was 60% (interquartile range, 60%–65%). CBFVs were correlated with arterial oxygen content, and C-reactive protein (Spearman ρ=0.28 [ P =0.04]; 0.58 [ P <0.001], respectively) but not with left ventricular ejection fraction (ρ=−0.18; P =0.42). Conclusions: In this cohort of critically ill patients with COVID-19 infection, we observed lower than expected CBFVs in setting of low arterial oxygen content and low hematocrit but not associated with suppression of cardiac output.

Use of hyperbaric oxygenation as an adjunctive treatment for severe pernicious anaemia in a bloodless medicine patient

Severe anaemia in patients who cannot receive blood transfusion is an indication for the use of hyperbaric oxygen therapy (HBO). Most reports of the use of HBO for anaemia involve patients with acute blood loss. This report details a case of HBO used for a patient with severe pernicious anaemia. A 35-year-old Jehovah’s Witnesses believer presented to a hospital with fatigue, dyspnoea and haemoglobin of 26 g/L. She was diagnosed with pernicious anaemia. As she could not receive blood transfusion due to her religious beliefs, vitamin B12 supplementation and HBO were administered and resulted in significant improvement in her condition. The mechanisms of action of HBO, including increased systemic plasma oxygenation, can alleviate signs and symptoms of anaemia regardless of its aetiology. HBO administration can greatly enhance the plasma arterial oxygen content, leading to clinical improvement in patients with anaemia who cannot receive blood transfusion.

Physiological impact of wearing a surgical face mask during walking in the COVID-19 pandemic

Background and Study Aim. Common use of surgical face masks is recommended for social and individual health due to the COVID-19 pandemic. However, there is no systematic report for responses of organism to wearing a surgical face mask during different exercises. In this context the purpose of this study was to examine the impacts of wearing a surgical face mask during a one-hour brisk walking. Material and Methods. A total of thirty male (n=16) and female (n=14) volunteers (mean age and BMI of 32±1.07 years and 25.1±0.68 kg/m2, respectively) completed the protocol. This was a multiple cross-over trial for healthy volunteers. All participants took a one-hour brisk walking with and without a surgical face mask. Specific physiological measurements (HR - heart rate; BP - blood pressure, SaO2 - arterial oxygen content) were compared before and immediately after two brisk walking. Each subject served their own control. Results. The evaluation found that there was no statistically significant difference between the mean HR and blood pressure values during the brisk walking with and without a surgical face mask, while there was a statistically significant difference in the SaO2 values on behalf of no-mask-walking (p<0.05). Conclusions. The use of surgical face masks in healthy volunteers causes a decrease in SaO2 during brisk walking. However, it does not affect the mean pulse rate and blood pressure. Although there was a statistically significant decrease in the SaO2 parameter during mask-walking, it is possible to state that brisk walking with a surgical face mask does not have a physiologically negative impact, because this decrease is in ranges that are accepted to be normal.

Geographical ancestry affects normal hemoglobin values in high-altitude residents

Increasing the hemoglobin (Hb) concentration is a major mechanism adjusting arterial oxygen content to decreased oxygen partial pressure of inspired air at high altitude. Approximately 5% of the world’s population living at altitudes higher than 1,500 m shows this adaptive mechanism. Notably, there is a wide variation in the extent of increase in Hb concentration among different populations. This short review summarizes available information on Hb concentrations of high-altitude residents living at comparable altitudes (3,500–4,500 m) in different regions of the world. An increased Hb concentration is found in all high-altitude populations. The highest mean Hb concentration was found in adult male Andean residents and in Han Chinese living at high altitude, whereas it was lowest in Ethiopians, Tibetans, and Sherpas. A lower plasma volume in Andean high-altitude natives may offer a partial explanation. Indeed, male Andean high-altitude natives have a lower plasma volume than Tibetans and Ethiopians. Moreover, Hb values were lower in adult, nonpregnant females than in males; differences between populations of different ancestry were less pronounced. Various genetic polymorphisms were detected in high-altitude residents thought to favor life in a hypoxic environment, some of which correlate with the relatively low Hb concentration in the Tibetans and Ethiopians, whereas differences in angiotensin-converting enzyme allele distribution may be related to elevated Hb in the Andeans. Taken together, these results indicate different sensitivity of oxygen dependent control of erythropoiesis or plasma volume among populations of different geographical ancestry, offering explanations for differences in the Hb concentration at high altitude.