Splenectomy impairs diffusive oxygen transport in the lung of dogs

Dane, D. Merrill; Hsia, Connie C. W.; Wu, Eugene Y.; Hogg, Richard T.; Hogg, Deborah C.; Estrera, Aaron S.; Johnson, Robert L.

doi:10.1152/japplphysiol.01600.2005

Cited by 26 publications

(39 citation statements)

References 41 publications

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“…During exercise more O 2 is required by the working skeletal muscles and thus a shift from the optimal physiological to the optimal Htc value for maximal endurance performance is observed. To cover their high O 2 demand during strenuous exercise, some terrestrial vertebrate species, such as horses and dogs, but not mice, release stored erythrocytes into the circulation by splenic contraction (26,27). This mechanism elevates the blood O 2 -carrying capacity during exercise within seconds.…”

Section: Discussionmentioning

confidence: 99%

Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice

Schuler

Arras

Keller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

104

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Erythropoietin (Epo) treatment increases hematocrit (Htc) and, consequently, arterial O 2 content. This in turn improves exercise performance. However, because elevated blood viscosity associated with increasing Htc levels may limit cardiac performance, it was suggested that the highest attainable Htc may not necessarily be associated with the highest attainable exercise capacity. To test the proposed hypothesis that an optimal Htc in acute and chronic Epotreated mice exists-i.e., the Htc that facilitates the greatest O 2 flux during maximal exercise-Htc levels of wild-type mice were acutely elevated by administering novel erythropoiesis-stimulating protein (NESP; wtNESP). Furthermore, in the transgenic mouse line tg6 that reaches Htc levels of up to 0.9 because of constitutive overexpression of human Epo, the Htc was gradually reduced by application of the hemolysis-inducing compound phenylhydrazine (PHZ; tg6PHZ). Maximal cardiovascular performance was measured by using telemetry in all exercising mice. Highest maximal O 2 uptake ( _ VO 2max ) and maximal time to exhaustion at submaximal exercise intensities were reached at Htc values of 0.58 and 0.57 for wtNESP, and 0.68 and 0.66 for tg6PHZ, respectively. Rate pressure product, and thus also maximal working capacity of the heart, increased with elevated Htc values. Blood viscosity correlated with _ VO 2max . Apart from the confirmation of the Htc hypothesis, we conclude that tg6PHZ adapted better to varying Htc values than wtNESP because of the higher optimal Htc of tg6PHZ compared to wtNESP. Of note, blood viscosity plays a critical role in limiting exercise capacity.blood viscosity | doping | excessive erythrocytosis | exercise performance | hemolysis

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Section: Discussionmentioning

confidence: 99%

Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice

Schuler

Arras

Keller

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

104

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“…Horses, for example, show a 65-75% increase of haematocrit during exercise (Boucher & Connes, 2008;Catalini, Dottavio, & Rasia, 2007), and greyhounds present a substantial increase in reticulocyte count (Horvath et al, 2014). Further, it has been demonstrated that these responses to exercise are abolished by splenectomy, both in horses (Kunugiyama et al, 1997) and in dogs (Dane, Hsi, Wu, Hogg, Hogg et al, 2006;Hsia et al, 1985;Vatner et al, 1974).…”

Section: Findings In Animal Experimentsmentioning

confidence: 99%

Responses of the human spleen to exercise

Shephard

2015

Journal of Sports Sciences

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The human spleen shows a decrease in volume of around 40% early during vigorous exercise and in response to other stressful stimuli such as maximal apnoea and the breathing of hypoxic gas mixtures. Contraction seems an active response, mediated by alpha-adrenergic fibres in the splenic nerve. Given the relatively small size of the human spleen, the effect upon physical performance is likely to be small; the augmentation of total blood volume is <2%, and even taking account of other causes of haemoconcentration during vigorous exercise, the increase of haematocrit is <10%. However, one of two studies suggested that the haemoconcentration may be sufficient to cause errors in the traditional method for calculating exercise-induced changes of plasma volume. The spleen also contributes leucocytes and platelets to the general circulation as part of the "fight or flight" reaction to stressors. The mobilisation of leucocytes proceeds more slowly than that of the red cells; it depends not only upon an active contraction of the spleen, but also a modulation of leucocyte adhesion molecules. Splenectomy impairs exercise performance in horses, but human performance data are lacking; overall health effects seem minimal, and many patients live many years after removal of their spleens.

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“…The technique has been described extensively (6,20,29). Based on individual performance, measurements were obtained at three to five workloads of differing intensities.…”

Section: Animalsmentioning

confidence: 99%

Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing capacity in exercising foxhounds

Hsia¹,

Wagner

Dane

et al. 2008

Journal of Applied Physiology

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(MIGET). The DLO 2 -to-DLCO ratio averaged 1.61. Correlation between DL O 2 (RB) and DLO 2 (MIGET) was similar in normal and post-resection groups. Overall, DL O 2 (MIGET) ϭ 0.975 DLO 2 (RB); mean difference between the two techniques was under 5% for both animal groups. We conclude that, despite various uncertainties inherent in these two disparate methods, the Roughton-Forster equation adequately predicts diffusive O 2 transfer from rest to heavy exercise in canines with normal, as well as reduced, lung capacities. oxygen-diffusing capacity; multiple inert-gas elimination technique; rebreathing technique; Roughton-Forster relationship; lung resection; dog THE IMPETUS FOR MEASURING lung diffusing capacity arose because two famous investigators (Christian Bohr and John Scott Haldane) reported in the 1890's using independent methods (2, 8) that O 2 was actively secreted into pulmonary capillary blood, so that O 2 tension of blood leaving the lung was higher than that in alveolar air. August and Marie Krogh (26,27) were skeptical of the secretion theory, owing to uncertainties in the techniques. Krogh and Bohr recognized a need to measure diffusing capacity using a gas other than O 2 to determine whether passive diffusion could support the levels of O 2 uptake during exercise. Haldane was the first to measure carbon monoxide (CO) uptake at rest on himself (7). Based on Haldane's measurements, Bohr (1) (24,30,42). Bohr also derived the famous Bohr integral to interpret the data but erroneously concluded that O 2 secretion was required to raise O 2 uptake above 1.5 l/min. Marie Krogh, using a breath-holding method, measured DL CO at rest and exercise (27) and showed that DL O 2 rose to two to four times that measured at rest by Bohr, sufficient to support O 2 uptake during exercise, even at high altitude, without invoking O 2 secretion. Thus diffusion was established as the process of O 2 transfer within pulmonary alveoli.Marie Krogh (27) in 1915 first proposed the use of DL CO to infer physiological limits of diffusive O 2 transfer, assuming DL O 2 Ϸ 1.23⅐DL CO , which took into account the relative tissue diffusivities for O 2 and CO, but not the relative conductance of capillary blood (⌰ O 2 and ⌰ CO , respectively, in ml gas⅐min Ϫ1 ⅐ml blood Ϫ1 ⅐mmHg Ϫ1 ). In the 1950's, Roughton and Forster (34) partitioned DL CO into separate resistances imposed by the alveolar membrane (Dm CO ) and capillary blood (⌰ CO ⅐Vc), i.e.,where ⌰ CO (ml CO⅐min Ϫ1 ⅐ml blood Ϫ1 ⅐mmHg Ϫ1 ) is the empirical CO uptake by whole blood measured in vitro, and Vc is pulmonary capillary blood volume (ml). Half a century later, the true values of ⌰ O 2 and ⌰ CO remain controversial, and no study has formally established whether Dm CO and Vc accurately predict diffusive O 2 transfer. Resistance of the blood for CO uptake is thought to be greater than that for O 2 uptake. There have been concerns that true Dm CO and Vc are sensitive to inspired O 2 tension (18), thereby introducing errors when inferring O 2 transfer from CO uptake measured at dif...

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Splenectomy impairs diffusive oxygen transport in the lung of dogs

Cited by 26 publications

References 41 publications

Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice

Optimal hematocrit for maximal exercise performance in acute and chronic erythropoietin-treated mice

Responses of the human spleen to exercise

Predicting diffusive alveolar oxygen transfer from carbon monoxide-diffusing capacity in exercising foxhounds

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