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Department of Bioengineering, University of California, La Jolla, California 92093-0412
Submitted 5 November 2003 ; accepted in final form 24 January 2004
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ABSTRACT |
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 TOP ABSTRACT METHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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shear stress; perfusion; plasma expander; blood pressure
The presumed universal benefit of instituting hemodilution with low-viscosity plasma expanders was challenged by Tsai et al. (32), who showed that microvascular function can only be maintained in extreme hemodilution if plasma viscosity is increased during the hemodilution process. This approach showed that in the awake hamster window chamber model, hemodilution could be carried to a hematocrit (Hct) of 11% (normally 46%) while preserving normal capillary flow if plasma viscosity was elevated to 
2.2 cP using Dextran 500 (molecular mass = 500,000 Da). Normal microvascular and cardiovascular function were evidenced by the maintenance of capillary perfusion and acid-base balance, microvascular flow maintained above control values, and maintenance of mean arterial blood pressure (MAP). Conversely, neither of these parameters/functions could be maintained at a systemic Hct of 11% if plasma viscosity was 1.1 cP as attained when Dextran 70 (molecular mass = 70,000 Da) was used as the hemodilutent.
The outcome obtained with the high-viscosity diluent is desirable because it maintains capillary perfusion, also termed functional capillary density (FCD), which is defined as the number of capillaries with passage of red blood cells (RBCs) per unit surface of the field of view of a microscopically observed tissue (20). This microvascular parameter was found to be critical in defining tissue survival by Kerger et al. (12), who showed that in extended hemorrhagic shock in awake hamsters. Maintenance of FCD above a specific threshold was the only functional factor observable at the microvascular level that differentiated surviving and nonsurviving animals (12).
The potential beneficial effect of high plasma viscosity in extreme hemodilution may be due to a combination of factors. High plasma viscosity may restore shear stress in the microcirculation leading to the production of vasodilators as postulated by the study of Frangos et al. (8). Increased plasma viscosity has also been associated with vasodilatation and increased microvascular flow (32). We hypothesize that high plasma viscosity and increased FCD may also be due to the direct transmission of central blood pressure to the periphery and the capillaries when microvascular flow is unimpeded by vasoconstriction
The present study was carried out to test the hypothesis that the use of high-viscosity plasma expanders in extreme hemodilution maintains FCD by maintaining capillary pressure. Extreme hemodilution can also be attained using OCPEs formulated with modified Hb molecules. Some of these products are vasoactive and therefore maintain central blood pressure through vasoconstriction, and their ability to carry oxygen may allow extreme hemodilution to be sustained with improved microvascular conditions relative to those realized with non-OCPEs. However, extreme hemodilution with these materials reduced FCD (31); thus, as a corollary to our hypothesis, we propose that this fall of FCD is a direct consequence of a fall in capillary pressure.
The preceding observations indicate that restoration of systemic conditions do not necessarily lead to the restoration of microvascular function. Therefore, the present study was also carried out to show that restoration of central blood pressure in pathophysiological conditions can be achieved by increasing peripheral vascular resistance through vasoconstriction, leading to a negative outcome in terms of capillary perfusion, and through the increase of plasma/blood viscosity, which leads to the restoration of microvascular function. To test these hypotheses, we measured microvascular pressures in extreme hemodilution with high- and low-viscosity plasma expanders and a low-viscosity oxygen-carrying vasoactive plasma expander, under the assumption that capillary pressure is the major determinant of FCD.
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METHODS |
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Inclusion criteria. Animals were suitable for the experiments if 1) systemic parameters were within normal range, namely, heart rate (HR) > 340 beat/min, MAP > 80 mmHg, systemic Hct > 45%, and arterial PO2 (PaO2) > 50 mmHg; and 2) microscopic examination of the tissue in the chamber observed under x650 magnification did not reveal signs of edema or bleeding.
Systemic parameters. MAP, mean venular pressure (MVP; jugular catheter), and HR were recorded continuously (MP 150, Biopac Systems; Santa Barbara, CA) except during the actual blood exchange. Hct was measured from centrifuged arterial blood samples taken in heparinized capillary tubes (Readacrit Centrifuge, Clay Adams, Division of Becton-Dickinson; Parsippany, NJ). Hb content was determined spectrophotometrically from a single drop of blood (B-Hemoglobin, Hemocue; Stockholm, Sweden).
Blood chemistry and rheological properties. Arterial blood was collected in heparinized glass capillaries (0.05 ml) and immediately analyzed for PaO2, arterial PCO2 (PaCO2), base excess, and pH (Blood Chemistry Analyzer 248, Bayer; Norwood, MA). The comparatively low PaO2 and high PaCO2 of these animals is a consequence of their adaptation to a fossorial environment. Blood samples for viscosity and colloid osmotic pressure measurements were quickly withdrawn from the animal with a heparinized 3-ml syringe at the end of the experiment for immediate analysis.
Blood samples were centrifuged, and colloid osmotic pressure in the plasma was measured using a membrane colloid osmometer (model 420, Wescor; Logan, UT). Calibration of the osmometer was made with a 5% albumin solution using a 30-kDa cutoff membrane (Amicon; Danvers, MA) (34). The viscosities of plasma and whole blood were determined with a cone and plate viscometer at a shear rate of 160 s–1 at 37°C (Dv-II+ Viscometer, Brookfield Engineering Laboratories; Middleboro, MA).
FCD. Capillaries are considered functional if RBCs transit though the capillary segments during a 45-s period. FCD was tabulated from the capillary lengths with RBC transit in an area comprising 10 successive microscopic fields (420 x 320 µm2). FCD (cm–1) is the total length of RBC-perfused capillaries divided by the area of the microscopic field of view.
Microhemodynamics.
Arteriolar and venular blood flow velocities were measured on-line by using the photodiode cross-correlation method (9) (Photo Diode/Velocity Tracker model 102B, Vista Electronics; San Diego, CA). The measured centerline velocity (V) was corrected according to vessel size to obtain the mean RBC velocity (17) A video image-shearing method was used to measure vessel diameter (D) (10). Blood flow (Q) was calculated from the measured values as Q = V x 
(D/2)2. Changes in arteriolar and venular diameter from baseline were used as indicators of a change in vascular tone. Wall shear stress (WSS) was defined by WSS = WSR x 
, where WSR is the wall shear rate given by 8VD–1 and is blood viscosity.
In conditions of extreme hemodilution with a Hct of 11%, the contribution of RBCs to the total viscosity of blood is linear and amounts to 0.70 cP, which is the difference between blood and plasma viscosity. According to Lipowsky and Firrell (16), the "...relationship between systemic arteriolar venular and systemic hematocrit is illustrated by a tendency toward equilibrium during extreme hemodilution," converging to an average value of the ratio between microvascular and systemic Hct of 0.7 for Hct 10%. Therefore, we corrected our extreme hemodilution viscosity data by linearly reducing the viscosity RBC contribution by 70%. The same procedure was used for the normal blood data, where the Hct reduction is 0.58 for arterioles and 0.68 for venules (16); however, because at normal Hct blood viscosity is not linearly proportional to Hct, we used actual viscosity versus Hct (dilution with hamster blood) data to obtain the corrected value for blood viscosity.
Microvascular pressure. Microvascular pressures were measured with the servo-nulling technique developed by Wiederhielm et al. (35). The principal features of this technique have been described in detail by Intaglietta and Tompkins (11). Briefly, the unknown intravascular pressure is compared with a known, controlled pressure, generated by a voltage-to-pressure converter. The comparison was made using the property of glass microneedles filled with saline described by Rubio and Zubieta (26). Alternating current (AC) excitation is used to measure the resistance of the plasma-saline interface in the glass microcannula. Signal loss due to shunting impedance is compensated by automatically increasing the microcannuale AC current excitation with amplitude and phase that precisely make up for the stray capacitance current loss produced by a feedback system. This voltage controls the amplifier gain, which generates the compensating current that is added to the pipette excitation current (11).
Micropipettes were pulled from glass capillary tubing [1 mm outer diameter (OD) x 0.5 mm inner diameter (ID), Omega dot, Frederick Haer & Bowdoinham] using a P-87 micropipette puller (Sutter Instruments; Novato, CA) and beveled on an Alumina abrasive plate 0.05 µm (Sutter Instruments). The resultant pipettes had two taper tips. The first taper had a relatively gentle slope leading to a barrel length of 10–20 µm (ID 30 µm). The second taper had a sharp slope leading to a barrel length of 5 µm (ID 1–4 µm) (5). The pipettes were filled using a MicroFil filling needle (World Precision Instruments; Sarasota, FL) with 2.0 M NaCl to prevent debris from accumulating and were stored at 4°C. The final direct current electrical resistance ranged from 0.5 to 2 M
. The pressure system was calibrated as previously described (6). The micropipette was controlled using a hydraulic joystick micromanipulator (MO-102, Narishige Scientific Instruments; Tokyo, Japan) adapted for use with an Olympus BX51WI microscope.
Pressure measurements were accepted only if the following criteria were satisfied: 1) the micropipette could be manipulated inside the vessel lumen without affecting the pressure tracing; 2) the pressure tracing was insensitive to small changes in the gain of the servo-null system; and 3) the pressure tracing returned to zero when the pipette was removed from the vessel but remained immersed into the superfusate (5).
Acute isovolemic hemodilution. Progressive hemodilution to a final systemic Hct level of 25% of baseline was accomplished with three isovolemic exchange steps. This protocol is described in detail in our previous reports (31). Briefly, the volume of each exchange-transfusion step was calculated as a percentage of the blood volume, estimated as 7% of the body weight. An acute anemic state was induced by lowering systemic Hct by 60% with two steps of progressive isovolemic hemodilution using 6% Dextran 70, referred to as exchange levels 1 and 2 (Fig. 1). Level 1 exchange was 40% of blood volume and level 2 and 3 exchanges were each 35% of blood volume.
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Experimental groups. Animals were randomly divided into three experimental groups based on the test solution used during the final step of the hemodilution. A group which did not undergo the hemodilution protocol served as the control for this study.
Experimental setup. The unanesthetized animals were placed in restraining tube with a longitudinal from which the window chamber projected outward. The animals were given 30 min to adjust to the tube environment before the control systemic parameters (MAP, HR, blood gases, and Hct) were measured. The conscious animal in the tube was then affixed to the microscopic stage of a transillumination intravital microscope (BX51WI, Olympus; New Hyde Park, NY). The tissue image was projected onto a charge-coupled device camera (COHU 4815) connected to a videocassette recorder (AG-7355, JVC) and viewed on a monitor. Measurements were carried out using a x40 (LUMPFL-WIR, numerical aperture 0.8, Olympus) water immersion objective. During micropressure measurements, observations were made with either a x10 (Leitz, Germany; numerical aperture 0.22) or a x20 (Leitz, Germany; numerical aperture 0.33) dry objective. For easier detection of RBC passage, the contrast between RBCs and tissue was enhanced with a BG12 (420 nm) bandpass filter.
Fields of observations and vessels were chosen for study at locations in the tissue where the vessels were in sharp focus. Detailed mappings were made of the chamber vasculature so that the same microvessels were studied throughout the experiment. After each exchange and the ensuing stabilization period, measurements were performed following the schedule shown in Fig. 1, where exchanges begin every hour, i.e., the second exchange commences exactly 1 h after the start of the first exchange. Blood samples were withdrawn from level 3 exchange animals at the end of the experiment for subsequent analysis of viscosity and colloid osmotic pressure.
The cover glass of the window chamber was removed at the completion of the microhemodynamics measurements after the third exchange, and the tissue preparation was superfused (5 ml/min) with a physiological salt solution of the following composition (in mM): 131.9 NaCl, 4.7 KCl, 2.0 CaCl2, 1.2 MgSO4, and 20.0 NaHCO3, with pH 7.4 at 37°C. The tissue was maintained at 33–34°C by the heated solution. The solution spread on the tissue as a thin film, drained into a platter, and was drawn off by suction. Under control conditions, the solution was equilibrated with 95% N2-5% CO2, which maintained suffusate pH at 7.4 and minimized O2 delivery from the superfusate to the tissue (27). Pressure measurements were initiated 20 min after glass window removal, a period that was found to allow the tissue to stabilize and present unchanged microvascular parameters, as shown in Fig. 2.
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RESULTS |
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Data groups. The baseline data set was obtained by combining data from all four experimental groups (n = 26). Similarly, level 1 and level 2 data sets were obtained by combining data from all three experimental groups in the hemodilution protocol (n = 18). One-way ANOVA on these data showed no significant differences in any of the systemic or microcirculatory parameters, therefore allowing for grouping of the data into one representative group for each of the three states: baseline (n = 26), Level 1 (n = 18), and level 2 (n = 18). The control group (n = 8) was used to directly compare parameters that could not be repeated at each level in each animal, namely, micropressure and blood rheology parameters.
Systemic parameters. The three experimental groups with exchange protocol showed a significant reduction of Hct after each exchange (50.4 ± 2.1% for baseline, 27.8 ± 1.9% for level 1, 18.3 ± 1.5% for level 2, 11.1 ± 0.9% for level 3 Dextran 70, 11.8 ± 0.8% for level 3 Dextran 500, and 11.3 ± 1.2% for level 3 PBH; P < 0.001 for all level 3 groups compared with baseline). Hb showed the same trend (16.2 ± 1.2 g/dl for baseline, 9.4 ± 0.6 g/dl for level 1, 6.0 ± 0.8 g/dl for level 2, 3.7 ± 0.5 g/dl for level 3 Dextran 70, 3.8 ± 0.6 g/dl for level 3 Dextran 500, and 6.7 ± 0.7 g/dl for level 3 PBH; P < 0.001 for all level 3 groups compared with baseline). The exchange using PBH did not show a statistically significant decrease in Hb content compared with the level 2 Hb, as expected.
MAP was not changed from baseline (98.9 ± 8.1 mmHg) after the level 1 exchange (91.4 ± 11.9 mmHg), and upon further hemodilution with Dextran 70 MAP decreased to 88.4 ± 10.5 mmHg at level 2 (see Table 2). At level 3, MAP decreased to 64.4 ± 7.5 mmHg (P < 0.05 vs. baseline) in the group that received Dextran 70. The group that received Dextran 500 likewise had a decrease in MAP to 79.6 ± 5.4 mmHg (P < 0.05 vs. baseline). However, the group that received PBH during the third exchange did not show a significant change in MAP (86.8 ± 9.7 mmHg). MVP was not affected during the exchanges through level 1 and level 2, but during the last exchange the Dextran 70 group dropped to 5.8 ± 2.1 mmHg (P < 0.05 vs. baseline) and the PBH group also decreased to 6.8 ± 2.7 mmHg (P < 0.05 vs. baseline). HR was not affected significantly during the hemodilution protocol.
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Microhemodynamics. The changes in the diameter, RBC velocity, and blood flow of large feeding and small arcading arterioles (range 36–95 µm) and small collecting venules and large venular vessels (range 34–146 µm) were measured after each hemodilution step. Figure 3A shows that arteriolar diameter was unchanged after level 1 exchange. Upon further blood exchange to level 2, arterioles dilated to 1.10 ± 0.30 (N = 54, where N is the number of vessels, P < 0.05) of baseline. This trend reversed after level 3 exchange with Dextran 70 and PBH, resulting in a slight arteriolar vasoconstriction to 0.93 ± 0.25 (Dextran 70, N = 18, P < 0.05) and 0.90 ± 0.28 (Dextran 70, N = 18, P < 0.05) of baseline. After the level 3 exchange with Dextran 500, arteriolar diameter remained dilated at 1.20 ± 0.31 (N = 18, P < 0.05) of baseline.
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Figure 3, C and D, show the change in RBC velocity in arterioles and venules as a function of blood Hb content. An increase in both arteriolar and venular RBC velocity was detected after level 1 exchange to 1.62 ± 0.47 (P < 0.05) and 1.42 ± 0.56 (P < 0.05) of baseline, respectively. After level 2 exchange, arteriolar RBC velocity remained increased from baseline (1.43 ± 0.57, P < 0.05), whereas venular RBC velocity returned to baseline levels. Level 3 exchange with Dextran 70 and PBH reduced arteriolar flow velocity to 0.80 ± 0.41 (Dextran 70, P < 0.05) and 0.69 ± 0.38 (PBH, P < 0.05) of baseline, respectively. Venular RBC velocity decreased after level 3 exchange with Dextran 70 to 0.76 ± 0.49 (P < 0.05) of baseline. Level 3 exchange using Dextran 500 did not present changes in arteriolar and venular RBC velocity.
The relationships between arteriolar and venular blood flow after the hemodilution protocols and Hb are presented in Fig. 4. The results are given as means ± SE to show the trend of this parameter calculated from vessel diameter and RBC velocity. Both arteriolar and venular blood flow were statistically increased from baseline after level 1 and level 2 exchange. Upon further hemodilution with Dextran 70, these increased levels could not be sustained, and blood flow was statistically reduced from baseline levels in both arterioles and venules. However, level 3 exchange with Dextran 500 and PBH caused the return of arteriolar blood flow to baseline levels.
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DISCUSSION |
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TOPABSTRACTMETHODSRESULTSDISCUSSIONGRANTSREFERENCES |
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Lipowsky (15) summarized the pressure data available for the mesentery, the cat tenuissimus muscle, and the rat spinotrapezious muscle, showing that the pressure difference between these size microvessels is significantly greater and that pressure distribution is highly asymmetric. An exception was the pressure distribution in the vascular network of the rabbit omentum, where the difference between the same-size vessel was 20 mmHg and the distribution between arterioles and venules was linear, which is similar to the findings in our study. The hamster testis is also a capillary network straddled by a low pressure differential, with pressure in 12.5-µm-diameter arterioles being 12.7 ± 0.7 mmHg and in 25-µm-diameter venules being 9.9 ± 0.7 mmHg according to Sweeney et al. (30).
The differences in pressure found in the smallest arteriolar and the collecting venules measured in each group was 4.5 ± 7.0 mmHg for control and for the level 3 exchanges were 3.1 ± 4.9 mmHg for Dextran 70, 3.2 ± 4.8 mmHg for Dextran 500, and 4.0 ± 7.0 for PBH. Thus the pressure gradient that drives flow through the capillary network is the same for all conditions, because these results are not statistically different; furthermore, it was comparatively small, 4.0 mmHg. Therefore, although the distribution of anatomy-dependent vascular resistance is asymmetric with its major fraction being located in the arteriolar side of the network (Fig. 7), capillary pressure can be determined with a small error by simply taking the midpoint pressure measured in the end arterioles and the collecting venules.
The finding that FCD is unaffected by the pressure gradient suggests exploring the relationship between FCD and the average transmural capillary pressure, as shown in Fig. 8, which presents the paired data (FCD vs. interpolated capillary pressure) in the network bracketed by the arterioles and venules measured. This graph shows a strong correlation between FCD and capillary pressure, indicating that a determinant factor in maintaining flow of RBCs in the capillaries at a given pressure gradient is the maintenance of a near-normal transmural pressure.
The phenomenon of capillary flow cessation after the lowering of local hydraulic pressure was documented by Lindbom and Arfors (14) in the rabbit tenuissimus muscle, where they reported that FCD was a direct function of the pressure delivered by the femoral artery, showing that FCD decreased in proportion to the lowering of blood pressure due to the occlusion of this supply vessel.
Capillary vascular hindrance must be inversely proportional to the number of capillaries that participate in carrying the network throughput; therefore, our findings that the measured arteriolar/venular pressure does not change even when FCD decreases by 50% must be due to hindrance of the capillary circulation being a minimal portion of the 4 mmHg that we measured as the pressure drop between small arterioles and venules. Furthermore, because the venular circulation following the capillaries may have an even smaller vascular resistance than the capillary network, it would appear that the major portion of this 4-mmHg pressure drop resides in the terminal arterioles.
The results obtained may in part be conditioned by the exposure of the preparation to the environment. To ensure that there were no unusual effects due to exposure, we measured in the same preparation the arteriolar diameter before window removal and during suffusion of the exposed tissue and found no significant differences between diameters, as shown in Fig. 2. The finding that arterioles constricted with the PBH exchange, lowering capillary pressure to the same level as that found in extreme hemodilution with Dextran 70, a condition paralleled by a significant decrease of central blood pressure, supports the contention that relative changes of capillary pressure found are directly related to the effects due to the changes in plasma viscosity and vasoactivity.
Normovolemic hemodilution to level 2 caused improved flow conditions even though plasma viscosity was normal. Extreme hemodilution to level 3 with high-viscosity plasma produced microhemodynamic and systemic conditions that were near normal and a level of shear stress that was 50% higher than control. In this situation, the endothelium is presumably stimulated to increase nitric oxide (NO) production, a situation in which shear stress, plasma viscosity, NO and prostacyclin production, central and capillary pressure, and FCD are intertwined factors (7). However, given the linear relationship between FCD and capillary pressure, it appears that capillary pressure is the determinant of FCD.
When PBH is present, lowered capillary pressure is due to vasoconstriction and the low blood and plasma viscosity. Microvascular shear stress level 3 hemodilution with PBH was the same as control, whereas capillary pressure was the lowest of all groups, indicating that shear stress per se is not sufficient to maintain FCD. Thus capillary pressure plays a major role in determining FCD, and shear stress alone is not sufficient to ensure microvascular function, if capillary pressure is not maintained above a threshold level.
Our findings indicate that a high-viscosity plasma expander is able to improve tissue perfusion through the restoration of FCD, a phenomenon documented by the measurement of FCD and flow in the study of Tsai et al. (32) and presently by the restoration of capillary pressure in this study. This phenomenon is in part due to the increase in peripheral vascular resistance and concomitant increase in MAP attained in the absence of vasoconstriction. It is notable that increasing or restoring blood pressure by means of a vasoactive material, such as PBH, does not result in either the restoration of capillary pressure or the restoration of FCD, the latter noted in a previous study by Tsai (31). This result is due to vasoconstriction interposing a significant resistance between central blood pressure and the peripheral capillary network via the reduction of arteriolar diameter. Conversely, the increase in vascular resistance caused by the increased plasma viscosity is not a phenomenon localized in a specific circulatory district, and, being a resistance that is uniformly distributed throughout the circulation, it does not necessarily prevent the transmission of central blood pressure to the periphery, as shown by mathematical modeling by Tsai and Intaglietta (33).
The direct dependance of capillary pressure on systemic pressure and blood viscosity found in this study is in contrast to the apparent regulation of capillary pressure found in normal subjects whose central blood pressure varies during isometric exercise, as shown by Shore et al. (29). This difference in responses is probably due to extreme hemodilution bringing the circulation beyond the autoregulatory range tested by their experiments (29). Thus, in the present experiments, in extreme hemodilution, the circulation appears on one hand to attempt to compensate for the significantly lowered oxygen-carrying capacity by vasodilatation while ensuing that overall lowering of hydraulic pressure leads to a capillary shutdown, because capillary pressure is no longer sufficient to maintain the patency of these conduits.
The results of the present study also allow us to compare the significance of considering systemic versus microvascular parameters in evaluating the efficacy of transfusion fluids used to restore or maintain circulatory volume. It is undeniable that the primary objective of maintaining circulatory volume is that of maintaining vascular filling and therefore blood pressure; however, the latter can also be attained via vasoconstriction, as shown in this and other studies by the increase of blood viscosity. The two modalities for restoring perfusion pressure, however, have different outcomes in terms of microvascular function, because vasoconstriction, while maintaining central blood pressure, a clinically observable parameter, does not necessarily result in the maintenance of capillary function. The significance of this process was shown by the study of Kerger et al. (12), who found that the maintenance of capillary function, particularly FCD, is the only critical microvascular parameter that differentiates the outcome between survivors and nonsurvivors in extended hemorrhagic shock. Conversely, restoration of blood pressure via the increase in blood viscosity produces a condition that facilitates the transmission of central blood pressure to the capillaries, thus pressurizing this compartment and improving tissue perfusion.
These experiments show that tissue perfusion at the capillary level is maintained by maintaining blood viscosity to near-normal levels by increasing plasma viscosity. In the present experiments, this occurs because central blood viscosity is also significantly reduced by the reduction of Hct. Thus blood viscosity in extreme hemodilution with high-viscosity plasma returns to 2.88 ± 0.36 cP, a value that is still significantly lower than the viscosity of whole blood for the normal animals, which is 4.21 ± 0.67 cP. The conditions of extreme hemodilution with low viscosity plasma brings overall blood viscosity to the level of 2.11 ± 0.24 cP; thus it would appear that the "viscosity threshold," i.e., the point at which the pressure distribution determined by blood viscosity is no longer able to sustain FCD, is somewhere between 2.10 and 2.90 cP. It should be noted that because high-viscosity plasma does not carry oxygen in significant amounts, this viscosity threshold appears to be independent of oxygen-carrying capacity and delivery and solely dependent on how viscosity and consequently hydraulic pressures are distributed in the circulation (Table 3).
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These findings show that the presence of high-viscosity plasma does not change systemic vascular resistance, contrary to the change predicted if systemic vascular resistance is a direct function blood viscosity. Such an effect could still be due to RBC aggregation due the addition of Dextran 500 if aggregation decreases blood viscosity, thus compensating for the increased plasma viscosity; however, this is unlikely in extreme hemodilution, where aggregation should have virtually no effect on lowering bulk flow viscosity but could have the opposite effect, i.e., increasing vascular resistance through microvessel occlusion, for which there was no evidence because FCD increased with high-viscosity hemodilution. The conclusion of this analysis is that the lack of difference in macrocirculatory resistance in the presence of a significant increased plasma viscosity in extreme hemodilution suggests that high plasma viscosity produces a vasodilatory effect, leading to increased capillary pressure.
The pressure data can be additionally analyzed in terms of relative changes of vascular resistance in the different vascular compartments to attempt to differentiate between anatomic and rheological factors as causes for the changes in capillary pressure. To accomplish this, the intravascular micropressures (Pi) were normalized relative to the inlet and outlet pressures of the network according to the formula
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FOOTNOTES |
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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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P < 0.05.
