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

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.

Measurement of the cardiac output in small animals by thermodilution.

Cardiac output (CO) measurements based on indicator dilution, microspheres, thermodilution and ultrasonic sensors are not suitable for small animals, because of limited blood volume, high heart rates and small caliber vessels that do not allow probe placement within the heart. We developed a modified thermodilution method to measure CO in awake animals weighing less than 100 g. Under anesthesia, the animal is instrumented with a jugular vein catheter placed proximal to the subclavian vein and a temperature probe in the carotid artery with the thermocouple positioned at the aortic arch. Two days after implantation, room temperature saline is injected (150 microl) into the jugular catheter and the temperature change recorded. This system uses the temperature probe as a digital feedback control: (1) to minimize recirculation error; (2) to adjust baseline temperature, thereby increasing sensitivity to small changes in temperature; and (3) to stabilize animal core temperature. The system was calibrated using a laboratory bench model with anatomically scaled components. CO was measured (n=29) in 16 hamsters (65-115 g), and was linearly related to body weight. Cardiac index (CI=CO/weight) was 197.0 +/- 18.8 (ml/min)/kg. Repeated measurements were made. This technique allows correlating systemic flow changes to be correlated to those measured in the microcirculation of window chamber preparations.