Paradoxical hypotension following increased hematocrit and blood viscosity

Abstract

-Hematocrit (Hct) of awake hamsters and CD-1 mice was acutely increased by isovolemic exchange transfusion of packed red blood cells (RBCs) to assess the relation between Hct and blood pressure. Increasing Hct 7-13% of baseline decreased mean arterial blood pressure (MAP) by 13 mmHg. Increasing Hct above 19% reversed this trend and caused MAP to rise above baseline. This relationship is described by a parabolic function (R 2 ϭ 0.57 and P Ͻ 0.05). Hamsters pretreated with the nitric oxide (NO) synthase (NOS) inhibitor N -nitro-L-arginine methyl ester (L-NAME) and endothelial NOS-deficient mice showed no change in MAP when Hct was increased by Ͻ19%. Nitrate/nitrite plasma levels of Hct-augmented hamsters increased relative to control and L-NAME treated animals. The blood pressure effect was stable 2 h after exchange transfusion. These findings suggest that increasing Hct increases blood viscosity, shear stress, and NO production, leading to vasodilation and mild hypotension. This was corroborated by measuring A1 arteriolar diameters (55.0 Ϯ 21.5 m) and blood flow in the hamster window chamber preparation, which showed statistically significant increased vessel diameter (1.04 Ϯ 0.1 relative to baseline) and microcirculatory blood flow (1.39 Ϯ 0.68 relative to baseline) after exchange transfusion with packed RBCs. Larger increases of Hct (Ͼ19% of baseline) led blood viscosity to increase Ͼ50%, overwhelming the NO effect through a significant viscosity-dependent increase in vascular resistance, causing MAP to rise above baseline values. nitric oxide; shear stress; vascular resistance; hypertension IT IS A GENERAL MEDICAL and clinical perception that an increase in blood viscosity may lead to short-and long-term negative physiological conditions, and there appears to be universal agreement that increased blood viscosity is a factor in hypertension. Lowering blood viscosity, however, is not advocated as a means for controlling hypertension with the exception of erythrocytosis, substantial Hct increases consequent to adaptation to high altitudes, and cardiovascular impairment in premature infants. These conditions represent extremes of an increase in blood viscosity and clearly must be corrected by lowering Hct, because the extreme excess of red blood cells (RBCs) is superfluous in providing adequate oxygen-carrying capacity and is in fact a hindrance to blood flow and therefore oxygen delivery.Clinical studies (14, 37) report a significant relationship between hypertension and high Hct levels. Hypertensive patients have higher Hct values than normotensive control individuals (23). Patients suffering from polycythemia vera or other erythrocytoses present with pathologically high Hcts leading to hypertension, thromboembolism, and other severe clinical complications (2, 15). There is evidence, however, that individuals, such as Peruvian miners, survive with Hct levels of 75-91% (18), suggesting the existence of an adaptive mechanism.Endothelial cells play a key role in the regulation of blood pressure and blood flow beca...

Human common carotid wall shear stress as a function of age and gender: a 12-year follow-up study

“…Concerning the interaction between viscosity and blood flow velocity, elevated blood viscosity could increase peripheral vascular hindrance, but usually for marked increases (Martini et al 2005); this, in turn, might contribute to reduce blood flow and blood flow velocity. About the relationship between viscosity and arterial diameter, it has been reported that in acute hemoconcentration experiments, the nitric oxide system is activated in order to increase the arterial diameter and finally keep shear stress constant (Martini et al 2005;Giannattasio et al 2002). Despite this, we could notice that viscosity elevation should not be the only cause of the increase of arterial diameter with aging in our population since we have recorded a shear stress decrease with aging.…”

Mean arterial pressure nonlinearity in an elastic circulatory system subjected to different hematocrits

“…However, in normal experimental animals subjected to small Hct changes, MAP decreased and cardiac output increased significantly as Hct was initially raised. This suggests that the oxygen autoregulatory control may not have a large gain for small changes in Hct (Martini et al 2005).…”

“…Under physiological conditions, the variability of blood viscosity is not sufficient to produce anomalous changes in MAP (Salazar-Vázquez et al 2006). However, Martini et al (2005) found that MAP decreased significantly when Hct was raised acutely in healthy hamsters, leading to a U-shaped MAP versus Hct distribution-a finding attributed to the competition between nitric oxide (NO) production by shear stress due to changes in blood viscosity and changes in resistance due to changes in blood viscosity. Salazar-Vázquez et al (2006) found a similar relationship in type 2 diabetic patients, when MAP was plotted as a function of the naturally occurring variability of Hct in the sampled population.…”

High-altitude diving in river otters: coping with combined hypoxic stresses

“…NO is a strong vasodilator, which diffuses from the endothelium and acts on soluble guanylyl cyclase in the vascular smooth muscle of blood vessels (Fleming and Busse, 2003;Ruschitzka et al, 2000). Endothelial NO production is stimulated by increases in viscosity-induced shear stress on vascular tissues (Furchgott and Vanhoutte, 1989;Martini et al, 2005). Consequently, moderate increases in Hct can lower blood pressure via NO-mediated vasodilatation (Martini et al, 2005;Salazar Vázquez et al, 2010;Wilcox et al, 1993).…”

“…Endothelial NO production is stimulated by increases in viscosity-induced shear stress on vascular tissues (Furchgott and Vanhoutte, 1989;Martini et al, 2005). Consequently, moderate increases in Hct can lower blood pressure via NO-mediated vasodilatation (Martini et al, 2005;Salazar Vázquez et al, 2010;Wilcox et al, 1993). The suggestion that otters may enhance NO production in response to increased blood viscosity is supported by the observation that the one dehydrated SJI individual showed exceedingly high levels of NO, coinciding with an elevated concentration of RBCs and raised Hct.…”