Hemodynamic response to normovolemic polycythemia at rest and during exercise in dogs.

Lindenfeld, JoAnn; Weil, John V.; Travis, Victoria L.; Horwitz, Lawrence D.

doi:10.1161/01.res.56.6.793

Cited by 14 publications

(17 citation statements)

References 29 publications

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“…The optimal Htc hypothesis is in disagreement with several studies (17,18). All of these authors provide evidence that O 2 delivery and thus exercise performance, including _ VO 2max , remained relatively constant with chronic excessive erythrocytosis.…”

mentioning

confidence: 76%

“…Thus, tg6PHZ might be able to adapt better to varying Htc levels than wtNESP. Physiological adaptations to excessive erythrocytosis are also observed in dogs and humans (17,18). Moreover, one case report in sport medicine describes a successful Finnish cross-country skier with an autosomal dominant mutation in Epo receptor that resulted in increased sensitivity of erythroid progenitors to Epo that ultimately led to Htc levels of 0.68 (17).…”

Section: Discussionmentioning

confidence: 99%

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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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mentioning

confidence: 76%

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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“…The issue is whether in our experiments, administration of methylene blue to hamsters with 32% methemoglobin could affect microvascular resistance (arteriolar diameter was reduced 30 min after infusion, but this was not statistically significant; P ϭ 0.14) through decreases in nitric oxide-mediated vasodilation rather than through a physiological response to the concomitant increase in oxygen-carrying capacity. Whereas intravenous methylene blue is highly effective in converting methemoglobin to oxyhemoglobin and is used for this purpose clinically, methylene blue could partially inhibit guanylate cyclase in the in vitro vascular segments preparations and in the in vivo models (24). Inhibition of guanylate cyclase prevents nitric oxide signaling (23,31).…”

Section: Discussionmentioning

confidence: 99%

Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity

Cabrales

Martini²,

Intaglietta³

et al. 2006

American Journal of Physiology-Heart and Circulatory Physiology

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Cabrales, Pedro, Judith Martini, Marcos Intaglietta, and Amy G. Tsai. Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity. Am J Physiol Heart Circ Physiol 291: H581-H590, 2006. First published March 3, 2006 doi:10.1152/ajpheart.01279.2005.-Responses to exchange transfusion with red blood cells (RBCs) containing methemoglobin (MetRBC) were studied in an acute isovolemic hemodiluted hamster window chamber model to determine whether oxygen content participates in the regulation of systemic and microvascular conditions during extreme hemodilution. Two isovolemic hemodilution steps were performed with 6% dextran 70 kDa (Dex70) until systemic hematocrit (Hct) was reduced to 18% (Level 2). A third-step hemodilution reduced the functional Hct to 75% of baseline by using either a plasma expander (Dex70) or blood adjusted to 18% Hct with all MetRBCs. In vivo functional capillary density (FCD), microvascular perfusion, and oxygen distribution in microvascular networks were measured by noninvasive methods. Methylene blue was administered intravenously to reduce methemoglobin (rRBC), which increased oxygen content with no change in Hct or viscosity from MetRBC. Final blood viscosities after the entire protocol were 2.1 cP for Dex70 and 2.8 cP for MetRBC (baseline, 4.2 cP). MetRBC had a greater mean arterial pressure (MAP) than did Dex70. FCD was substantially higher for MetRBC [82 (SD 6) of baseline] versus Dex70 [38 (SD 10) of baseline], and reduction of methemoglobin to oxyhemoglobin did not change FCD [84% (SD 5) of baseline]. PO2 levels measured with palladium-meso-tetra(4-carboxyphenyl)porphyrin phosphorescence were significantly changed for Dex70 and MetRBC compared with Level 2 (Hct 18%). Reduction of methemoglobin to oxyhemoglobin partially restored PO2 to Level 2. Wall shear rate and wall shear stress decreased in arterioles and venules for Dex70 and did not change for MetRBC or rRBC. Increased MAP and shear stress-mediated factors could be the possible mechanisms that improved perfusion flow and FCD after exchange for MetRBC. Thus the fall in systemic and microvascular conditions during extreme hemodilution with low-viscosity plasma expanders seems to be, in part, from the decrease in blood viscosity independent of the reduction in oxygen content. microcirculation; extreme hemodilution; plasma expander; intravascular oxygen; methemoglobin; methylene blue; functional capillary density CORRECTION OF BLOOD LOSSES commences with the initial restitution of volume by means of plasma expanders, followed by the reinstatement of oxygen-carrying capacity via blood transfusion on reaching the so-called transfusion trigger. Multiple factors are responsible for reaching this point, including the amount of the blood loss and the dilution due to fluid infused to restore volume. As anemia progresses, oxygenation becomes a concern, when the oxygen-carrying capacity may be insufficient to supply the metabolic demand, and a blood transfusion is performed. The le...

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“…However, the physical characteristics of red cells alter blood turbulence, and thereby beneficially affect blood viscosity, coagulability, atherosclerosis, and hemodynamic efficiency [381][382][383][384][385].…”

Section: The Turbulence Mechanismmentioning

confidence: 99%

Stress repair mechanism activity explains inflammation and apoptosis

Coleman¹

2012

ABB

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Hemodynamic response to normovolemic polycythemia at rest and during exercise in dogs.

Cited by 14 publications

References 29 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

Blood viscosity maintains microvascular conditions during normovolemic anemia independent of blood oxygen-carrying capacity

Stress repair mechanism activity explains inflammation and apoptosis

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