Elevated plasma viscosity in extreme hemodilution increases perivascular nitric oxide concentration and microvascular perfusion

Abstract

We tested the hypothesis that high-viscosity (HV) plasma in extreme hemodilution causes wall shear stress to be greater than low-viscosity (LV) plasma, leading to enhanced production of nitric oxide (NO). The perivascular concentration of NO was measured in arterioles and venules and the tissue of the hamster chamber window model, subjected to acute extreme hemodilution, with a hematocrit (Hct) of 11% using Dextran 500 (n = 6) or Dextran 70 (n = 5) with final plasma viscosities of 1.99 +/- 0.11 and 1.33 +/- 0.04 cp, respectively. HV plasma significantly increased the periarteriolar, perivenular, and tissue NO concentration by 2.0, 1.9, and 1.4 times the control (n = 7). The NO concentration with LV plasma was not statistically different from control. Arteriolar shear stress was significantly increased in HV plasma relative to LV plasma in arterioles but not in venules. Aortic endothelial NO synthase (eNOS) protein expression was increased with HV plasma but not with LV plasma. There was a weak correlation between perivascular NO concentration and the locally calculated shear stress induced by the procedures, when blood viscosity was corrected according to Hct values previously determined in studies of microvascular Hct distribution. The finding that the periarteriolar and venular NO concentration in HV plasma was the same although arteriolar shear stress was significantly greater than venular shear stress maybe be due to differences in vessel wall metabolism between arterioles and venules and the presence of NO transport through the blood stream in the microcirculation. Results support the concept that in extreme hemodilution HV plasma maintains functional capillary density through a NO-mediated vasodilatation.

Increased plasma viscosity prolongs microhemodynamic conditions during small volume resuscitation from hemorrhagic shock

“…Furthermore, this restoration can be sustained and improved if blood rheological properties, especially plasma viscosity, are manipulated to reinstate endothelium mechanical signals at the hypovolemic and anemic states. 21 The role of plasma viscosity and consequently blood viscosity in maintaining systemic blood pressure and blood gases are highlighted by the results obtained here, since increasing plasma viscosity by the means of alginate provided consistent restoration of homeostasis compared to volume resuscitation with Hextend alone. Although Hextend's high molecular weight results in a higher viscosity than other hydroxyethyl starch solutions, the addition of a viscogenic agent improved recovery of microhemodynamic conditions.…”

“…A previous study by Tsai et al showed that increased shear stress due to moderate augmentation of plasma viscosity was associated with increased concentration of perivascular microvascular nitric oxide and vasodilation. 21 Current studies show that the resuscitation limit for hemorrhagic shock is reached when blood viscosity is severely decreased by blood dilution, causing the impairment of microvascular function, local blood flow mal-distribution and insufficient oxygen delivery. [24][25][26] Deliberate hypotensive resuscitation by a limited volume infusion is suitable for conditions where bleeding has stopped but definitive control of bleeding has not been attained, a condition typical of pre-hospital settings.…”

Intravital microscopy in a dorsal skinfold chamber: hemodynamics, tumor angiogenesis and inflammation

“…The dorsal skinfold chamber model such as this has been established in rats 1 , mice 2 , nude mice [3][4][5][6] , as well as in hamsters. [7][8][9][10][11] The dorsal skinfold chamber can easily be positioned under an upright microscope for intravital microscopic analyses of the microcirculation. One of titanium frame has a circular cover glass slip with a retaining ring.…”

“…A microvascular diameter measurement has been performed before and after intervention in many experimental conditions such as hemorrhagic shock resuscitation and acute hemodilution. 10,[22][23][24] By measured microvascular diameter, the vasomotor response can be observed as well as calculated microvascular resistance. 25 In addition, to estimate blood flow rate, for which it is necessary to know the vascular diameter and blood flow velocity.…”

“…Tsai and colleague used microelectrodes coated with Nafion to measure perivascular NO at the end of microhemodynamic measurement by removing a coverglass of dorsal skinfold chamber. 10 In their process, perivascular tissue was prepared before penetrating the micropipette with microelectrode. However, this study was done at the end of study, not during the experiment, which can not provide information at other time points.…”