The Perfusion Paradox and Vascular Instability in Sickle Cell Disease

Nath, Karl A.; Katušić, Zvonimir S.; Gladwin, Mark T.

doi:10.1080/10739680490278592

Cited by 83 publications

(73 citation statements)

References 119 publications

(193 reference statements)

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“…In view of the marked increase in blood flow that occurred in wild-type mice following the creation of an AVF, we posited that a disease that exhibits impaired hemodynamic responses would fail to mount the expected increase in AVF flow and preservation of AVF function. The rheologic abnormalities in SCD have long been recognized (11,25), and our prior studies demonstrated that the vasculature in a transgenic murine model of SCD exhibits impairment in endothelium-dependent and endothelium-independent vasorelaxant responses (26). We thus employed this murine model as a representative disease to test this hypothesis.…”

Section: Resultsmentioning

confidence: 88%

“…We next sought to determine the contribution of a vasorelaxant system, specifically, heme oxygenase-1 (HO-1), in enabling the augmented blood flow that occurs in the AVF. Finally, to examine whether AVF flow and function would be compromised in a representative disease attended by impaired hemodynamic responses, AVF blood flow and patency were assessed in a murine disease model in which critical aspects of hemodynamic responses (vasorelaxation and blood rheology) are known to be substantially perturbed (11,25,26).…”

mentioning

confidence: 99%

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Regional and systemic hemodynamic responses following the creation of a murine arteriovenous fistula

Yamada²,

Hernandez

et al. 2011

American Journal of Physiology-Renal Physiology

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The study of hemodynamic alterations following the creation of an arteriovenous fistula (AVF) is relevant to vascular adaptive responses and hemodialysis access dysfunction. This study examined such alterations in a murine AVF created by anastomosing the carotid artery to the jugular vein. AVF blood flow was markedly increased due to reduced AVF vascular resistance. Despite such markedly increased basal blood flow, AVF blood flow further increased in response to acetylcholine. This AVF model exhibited increased cardiac output and decreased systemic vascular resistance; the kidney, in contrast, exhibited decreased blood flow and increased vascular resistance. Augmentation in AVF blood flow was attended by increased arterial heme oxygenase-1 (HO-1) mRNA and protein expression, the latter localized to smooth muscle cells of the AVF artery; AVF blood flow was substantially reduced in HO-1(-/-) mice compared with HO-1(+/+) mice. Finally, in a murine model of a representative disease known to exhibit impaired hemodynamic responses (sickle cell disease), the creation of an AVF was attended by decreased AVF flow and impaired AVF function. We conclude that this AVF model exhibits markedly increased AVF blood flow, a vasodilatory reserve capacity, increased cardiac output, decreased renal blood flow, and a dependency on intact hemodynamic responses, in general, and HO-1 expression, in particular, in achieving and maintaining AVF blood flow. We suggest that these findings support the utility of this model in investigating the basis for and the consequences of hemodynamic stress, including shear stress, and the pathobiology of hemodialysis AVF dysfunction.

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Section: Resultsmentioning

confidence: 88%

mentioning

confidence: 99%

Regional and systemic hemodynamic responses following the creation of a murine arteriovenous fistula

Yamada²,

Hernandez

et al. 2011

American Journal of Physiology-Renal Physiology

Self Cite

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“…It has been reported that this may be a consequence of important haemorheological mechanisms such as the Fahraeus-Lindquist effect. [7][8][9] Moreover, marginal variations may exist between the recorded values and actual microcirculatory oxygen delivery, as all viscosity studies, including the present study, have used samples taken from venous blood and then extrapolation made regarding delivery to tissues.…”

Section: Discussionmentioning

confidence: 99%

Oxygen delivery index in homozygous sickle cell disease: steady and crisis states

Bowers

Pepple

Reid

2009

British Journal of Biomedical Science

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One of the common complications of sickle cell disease is the vaso-occlusive crisis or sickle cell crisis which could result in impaired oxygen delivery to the tissues. This study investigates the oxygen delivery index (ODI) in 38 patients with homozygous sickle cell anaemia. Thirty-three patients were in the steady state and five were experiencing crisis at the time of recruitment. Whole blood viscosity was measured with a Wells Brookfield viscometer at a shear rate of 230 sec(-1) and haematocrit was measured with an AC Tron Coulter Counter. The ODI, which is an indirect measure of the capacity of blood to deliver oxygen to tissues, was calculated as the ratio of haematocrit to whole blood viscosity values. There was no statistically significant difference in the ODI between the steady and crisis states, suggesting that tissue oxygenation is not the only factor involved in the sickle cell crisis.

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“…56,56b,60 As such, plasma hemoglobin-free and oxygen-free radical-mediated consumption of nitric oxide produces a state of resistance to nitric oxide in patients with sickle cell disease. 56,58,[61][62][63][64][65] Downstream effects of hemolytic anemia include increased endothelin-1 expression, hememediated and free iron-mediated oxygen radical generation, platelet activation, and increased endothelial adhesion molecule expression. 4,56,[66][67][68] In patients with sickle cell disease, plasma endothelin-1 levels are increased in steady state and during crisis.…”

Section: Hemolysismentioning

confidence: 99%