Plasma viscosity regulates systemic and microvascular perfusion during acute extreme anemic conditions

2006 ◽  
Vol 291 (5) ◽  
pp. H2445-H2452 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai
Keyword(s):  
Flow Distribution ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Arterial Blood ◽  
Chamber Model ◽  
Kidney Liver ◽  
Window Chamber

The hamster window chamber model was used to study systemic and microvascular hemodynamic responses to extreme hemodilution with low- and high-viscosity plasma expanders (LVPE and HVPE, respectively) to determine whether plasma viscosity is a factor in homeostasis during extreme anemic conditions. Moderated hemodilution was induced by two isovolemic steps performed with 6% 70-kDa dextran until systemic hematocrit (Hct) was reduced to 18% ( level 2). In a third isovolemic step, hemodilution with LVPE (6% 70-kDa dextran, 2.8 cP) or HVPE (6% 500-kDa dextran, 5.9 cP) reduced Hct to 11%. Systemic parameters, cardiac output (CO), organ flow distribution, microhemodynamics, and functional capillary density, were measured after each exchange dilution. Fluorescent-labeled microspheres were used to measure organ (brain, heart, kidney, liver, lung, and spleen) and window chamber blood flow. Final blood and plasma viscosities after the entire protocol were 2.1 and 1.4 cP, respectively, for LVPE and 2.8 and 2.2 cP, respectively, for HVPE (baseline = 4.2 and 1.2 cP, respectively). HVPE significantly elevated mean arterial pressure and CO compared with LVPE but did not increase vascular resistance. Functional capillary density was significantly higher for HVPE [87% (SD 7) of baseline] than for LVPE [42% (SD 11) of baseline]. Increases in mean arterial blood pressure, CO, and shear stress-mediated factors could be responsible for maintaining organ and microvascular perfusion after exchange with HVPE compared with LVPE. Microhemodynamic data corresponded to microsphere-measured perfusion data in vital organs.

Plasma viscosity regulates capillary perfusion during extreme hemodilution in hamster skinfold model

1998 ◽  
Vol 275 (6) ◽  
pp. H2170-H2180 ◽  
Author(s):  
Amy G. Tsai ◽  
Barbara Friesenecker ◽  
Michael McCarthy ◽  
Hiromi Sakai ◽  
Marcos Intaglietta
Keyword(s):  
Molecular Weight ◽  
Shear Stress ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
Capillary Perfusion ◽  
Low Viscosity ◽  
Arterial Blood ◽  
Wall Shear ◽  
Stress Dependent

Effect of increasing blood viscosity during extreme hemodilution on capillary perfusion and tissue oxygenation was investigated in the awake hamster skinfold model. Two isovolemic hemodilution steps were performed with 6% Dextran 70 [molecular weight (MW) = 70,000] until systemic hematocrit (Hct) was reduced by 65%. A third step reduced Hct by 75% and was performed with the same solution [low viscosity (LV)] or a high-molecular-weight 6% Dextran 500 solution [MW = 500,000, high viscosity (HV)]. Final plasma viscosities were 1.4 and 2.2 cP (baseline of 1.2 cP). Hct was reduced to 11.2 ± 1.1% from 46.2 ± 1.5% for LV and to 11.9 ± 0.7% from 47.3 ± 2.1% for HV. HV produced a greater mean arterial blood pressure than LV. Functional capillary density (FCD) was substantially higher after HV (85 ± 12%) vs. LV (38 ± 30%) vs. baseline (100%).[Formula: see text] levels measured with Pd-porphyrin phosphorescence microscopy were not statistically changed from baseline until after the third hemodilution step. Wall shear rate (WSR) decreased in arterioles and venules after LV and only in arterioles after HV. Wall shear stress (WSR × plasma viscosity) was substantially higher after HV vs. LV. Increased mean arterial pressure and shear stress-dependent release of endothelium-derived relaxing factor are possible mechanisms that improved arteriolar and venular blood flow and FCD after HV vs. LV exchange protocols.

Microvascular pressure and functional capillary density in extreme hemodilution with low- and high-viscosity dextran and a low-viscosity Hb-based O2 carrier

2004 ◽  
Vol 287 (1) ◽  
pp. H363-H373 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai ◽  
Marcos Intaglietta
Keyword(s):  
Blood Pressure ◽  
Capillary Pressure ◽  
Arterial Blood Pressure ◽  
Mean Arterial Blood Pressure ◽  
Capillary Density ◽  
High Viscosity ◽  
Functional Capillary Density ◽  
Plasma Expander ◽  
Arterial Blood ◽  
Plasma Expanders

Blood losses are usually corrected initially by the restitution of volume with plasma expanders and subsequently by the restoration of oxygen-carrying capacity using either a blood transfusion or possibly, in the near future, oxygen-carrying plasma expanders. The present study was carried out to test the hypothesis that high-plasma viscosity hemodilution maintains perfused functional capillary density (FCD) by preserving capillary pressure. Microvascular pressure responses to extreme hemodilution with low- (LV) and high-viscosity (HV) plasma expanders and an exchange transfusion with a polymerized bovine cell-free Hb (PBH) solution were analyzed in the awake hamster window chamber model ( n = 26). Systemic hematocrit was reduced from 50% to 11%. PBH produced a greater mean arterial blood pressure than the nonoxygen carriers. FCD was higher after a HV plasma expander (70 ± 15%) vs. PBH (47 ± 12%). Microvascular pressure spanning the capillary network was higher after a HV plasma expander (16–19 mmHg) compared with PBH (12–16 mmHg) and a LV plasma expander (11–14 mmHg) but lower than control (22–26 mmHg). FCD was found to be directly proportional to capillary pressure. The use of a HV plasma expander in extreme hemodilution maintained the number of perfused capillaries and tissue perfusion by comparison with a LV plasma expander due to increased mean arterial blood pressure and capillary pressure. The use of PBH increased mean arterial pressure but reduced capillary pressure due to vasoconstriction and did not maintain FCD.

Microvascular oxygen distribution in awake hamster window chamber model during hyperoxia

2003 ◽  
Vol 285 (4) ◽  
pp. H1537-H1545 ◽  
Author(s):  
Amy G. Tsai ◽  
Pedro Cabrales ◽  
Robert M. Winslow ◽  
Marcos Intaglietta
Keyword(s):  
Capillary Density ◽  
Microvascular Blood Flow ◽  
Oxygen Distribution ◽  
Microvascular Network ◽  
Normobaric Hyperoxia ◽  
Arterial Blood ◽  
Hyperoxic Condition ◽  
Direct Measurements ◽  
Chamber Model ◽  
Window Chamber

The microvascular effects and hemodynamic events following exposure to normobaric hyperoxia (because of inspiration of 100% O2) were studied in the awake hamster window chamber model and compared with normoxia. Hyperoxia increased arterial blood Po2 to 477.9 ± 19.9 from 60.0 ± 1.2 mmHg ( P < 0.05). Heart rate and blood pressure were unaltered, whereas cardiac index was reduced from 196 ± 13 to 144 ± 31 ml · min–1 · kg–1 ( P < 0.05) in hyperoxia. Direct measurements in the microcirculation showed there was arteriolar vasoconstriction, reduction of microvascular flow (83% of control, P < 0.05), and functional capillary density (FCD, 74 ± 16% of control), the latter change being significant ( P < 0.05). Calculations of oxygen delivery and oxygen consumption based on the measured changes in microvascular blood flow velocity and diameter and estimates of oxygen saturation corrected for the Bohr effect due to the lowered pH and increased Pco2 showed that oxygen transport in the microvascular network did not change between normal and hyperoxic condition. The congruence of systemic and microvascular hemodynamics events found with hyperoxia suggests that the microvascular findings are common to most tissues in the organism, and that hyperoxia, due to vasoconstriction and the decrease of FCD, causes a maldistribution of perfusion in the microcirculation.

scholarly journals Tissue oxidative metabolism after extreme hemodilution with PEG-conjugated hemoglobin

2010 ◽  
Vol 109 (6) ◽  
pp. 1852-1859 ◽  
Author(s):  
Pedro Cabrales ◽  
Fantao Meng ◽  
Seetharama A. Acharya
Keyword(s):  
Energy State ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Acid Base Balance ◽  
Noninvasive Technique ◽  
Isovolemic Hemodilution ◽  
Blood Flows ◽  
Arterial Blood ◽  
Base Balance ◽  
Chamber Model

NADH-localized fluorometry was used as a noninvasive technique to monitor changes in the energy state of intact tissue (muscle and connective tissue), without anesthesia, as a function of blood plasma O2-carrying capacity in the hamster window chamber model. Acute moderate isovolemic hemodilution was induced by two isovolemic hemodilution steps: in the first step, 6% 70-kDa dextran (Dex70) was used to induce an acute anemic state (18% Hct); in the second step, exchange transfusion of polyethylene glycol (PEG) maleimide-conjugated Hb (4 g/dl, PEG-Hb) or Dex70 (6 g/dl) was used to reduce erythrocytes to 75% of baseline (11% Hct). PEG-Hb had six copies of PEG (5 kDa) conjugated to each human Hb (0.48 g PEG/g Hb) through extension arm-facilitated chemistry. Systemic parameters, microvascular perfusion, functional capillary density, intravascular and interstitial Po2, and intracellular NADH fluorescence were monitored. Mean arterial blood pressure after extreme hemodilution was statistically significantly reduced for Dex70 compared with PEG-Hb. The presence of PEG-Hb in the circulation maintained positive acid-base balance. While microvascular blood flows were not different, functional capillary density was significantly higher for PEG-Hb than Dex70. Arteriolar Po2 was higher in the presence of PEG-Hb than Dex70, but tissue and venular Po2 were not different. Cellular energy metabolism (intracellular O2) in the tissues was improved with PEG-Hb. Moderate hemodilution to 18% Hct (6.4 g Hb/dl) brings tissue O2 delivery to the verge of inadequacy. Extreme hemodilution to 11% Hct (3.7 g Hb/dl) produces tissue anoxia, and high-O2-affinity PEG-Hb (Po2 at which blood is 50% saturated with O2 = 4 Torr, 1.1 g Hb/dl) only partially decreases anaerobic metabolism without increasing tissue Po2.

Alginate plasma expander maintains perfusion and plasma viscosity during extreme hemodilution

2005 ◽  
Vol 288 (4) ◽  
pp. H1708-H1716 ◽  
Author(s):  
Pedro Cabrales ◽  
Amy G. Tsai ◽  
Marcos Intaglietta
Keyword(s):  
Oxygen Consumption ◽  
Capillary Density ◽  
High Viscosity ◽  
Plasma Viscosity ◽  
The Other ◽  
Plasma Expander ◽  
Low Viscosity ◽  
Microvascular Changes ◽  
Dextran 70 ◽  
Window Chamber

Extreme hemodilution was performed in the hamster chamber window model using 6% Dextran 70, lowering systemic hematocrit by 60%. Animals were subsequently divided into three groups and hemodiluted to a hematocrit of 11% using 6% Dextran 70, 6% Dextran 500, and a 4% Dextran 70 + 0.7% alginate solution ( n = 6 each group). Final plasma viscosities were 1.4 ± 0.2, 2.2 ± 0.1, and 2.7 ± 0.2 cp, respectively, ( P < 0.05, high viscosity vs. low viscosity). Blood viscosities were 2.1 ± 0.2, 2.9 ± 0.4, and 3.9 ± 0.3 cp, respectively. The lowest blood and plasma viscosity group had a significantly lower functional capillary density, 37 ± 16%, whereas the two high-viscosity solutions were 71 ± 15% and 76 ± 12% ( P < 0.05, high viscosity vs. low viscosity), respectively. Arteriolar and venular flow in the Dextran 500 and alginate groups was higher than baseline (i.e., normal nontreated animals), whereas the low-viscosity group showed a reduction in flow. These microvascular changes were paralleled by changes in base excess, which was negative for the Dextran 70 group and positive for the other groups. However, tissue Po2 was uniformly low for all groups (average of 1.4 mmHg). Calculation of tissue oxygen consumption in the window chamber based on the microvascular data, flow, and intravascular Po2 showed that only the alginate + Dextran 70 solution-exchanged animals returned to baseline oxygen consumption, whereas the other groups were lower than baseline ( P < 0.05). These results show that hemodilution performed with high-viscosity plasma expanders yields systemic arterial pressures and functional capillary densities that are significantly higher ( P < 0.05) than those obtained with 6% Dextran 70, a fluid whose viscosity is similar to that of plasma. A condition for obtaining these results is that the oncotic pressure of the plasma expander be titrated to near normal, so that autotransfusion of fluid from the tissue into the vascular compartment does not reduce the effects of increasing plasma viscosity and increased shear stress on the microvascular wall.

scholarly journals Aging is associated with an increased susceptibility to ischaemic necrosis due to microvascular perfusion failure but not a reduction in ischaemic tolerance

2007 ◽  
Vol 112 (8) ◽  
pp. 429-440 ◽  
Author(s):  
Yves Harder ◽  
Michaela Amon ◽  
Mirko Georgi ◽  
Claudia Scheuer ◽  
Rene Schramm ◽  
...  
Keyword(s):  
Capillary Flow ◽  
Age Groups ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Microvascular Perfusion ◽  
Tissue Necrosis ◽  
Significant Difference ◽  
Ischaemic Necrosis ◽  
Increased Susceptibility ◽  
Capillary Dilation

In the present study in a murine model of chronic ischaemia, we analysed: (i) whether aging was associated with an increased susceptibility to ischaemic necrosis, and (ii) whether this was based on microvascular dysfunction or reduced ischaemic tolerance. An ischaemic pedicled skin flap was created in the ear of homozygous hairless mice. The animals were assigned to three age groups, including adolescent (2±1 months), adult (10±2 months) and senescent (19±3 months). Microvascular perfusion of the ischaemic flap was assessed over 5 days by intravital microscopy, evaluating FCD (functional capillary density), capillary dilation response and the area of tissue necrosis. Expression of the stress-protein HO (haem oxygenase)-1 was determined by immunohistochemistry and Western blotting. Induction of chronic ischaemia stimulated a significant expression of HO-1 without a significant difference between the three age groups. This was associated with capillary dilation, which, however, was more pronounced in adolescent (10.5±2.8 μm compared with 3.95±0.79 μm at baseline) and adult (12.1±3.1 μm compared with 3.36±0.45 μm at baseline) animals compared with senescent animals (8.5±1.7 μm compared with 3.28±0.69 μm at baseline; P value not significant). In senescent animals, flap creation further resulted in complete cessation of capillary flow in the distal area of the flap (FCD, 0±0 cm/cm2), whereas adult (11.9±13.5 cm/cm2) and, in particular, adolescent animals (58.4±33.6 cm/cm2; P<0.05) were capable of maintaining residual capillary perfusion. The age-associated microcirculatory dysfunction resulted in a significantly increased flap necrosis of 49±8% (P<0.05) and 42±8% (P<0.05) in senescent and adult animals respectively, compared with 31±6% in adolescent mice. Of interest, functional inhibition of HO-1 by SnPP-IX (tin protoporphyrin-IX) in adolescent mice abrogated capillary dilation, decreased functional capillary density and aggravated tissue necrosis comparably with that observed in senescent mice. Thus aging is associated with an increased susceptibility to tissue necrosis, which is due to a loss of vascular reactivity to endogenous HO-1 expression, rather than a reduction in ischaemic tolerance.

Diaphragmatic microcirculation during halothane and isoflurane exposure in pentobarbital-anesthetized rats

1992 ◽  
Vol 73 (4) ◽  
pp. 1614-1618 ◽  
Author(s):  
A. Leon ◽  
J. Boczkowski ◽  
B. Dureuil ◽  
E. Vicaut ◽  
M. Aubier ◽  
...  
Keyword(s):  
Capillary Density ◽  
Baseline Period ◽  
Functional Capillary Density ◽  
Dependent Manner ◽  
Minimal Alveolar Concentration ◽  
Arterial Blood ◽  
Anesthetized Rats ◽  
Isoflurane Group ◽  
Dose Dependent

We investigated the effects of halothane and isoflurane on diaphragmatic microcirculation in pentobarbital-anesthetized rats by in vivo video microscopy. After a baseline period, rats were randomly allocated into three groups according to administration of 0.5, 0.75, and 1 minimal alveolar concentration (MAC) of either halothane (group Hal, n = 16), isoflurane (group Iso, n = 14), or no halogenated agent (group C, n = 20) in three succeeding steps of 15 min. Mean arterial blood pressure (MAP), arteriolar diameters, and functional capillary density were analyzed in the last 3 min of each step. MAP remained unchanged in group C but decreased in a dose-dependent manner in both halogenated receiving groups. MAP was significantly lower in rats breathing Hal compared with those breathing Iso. Arterioles were classified in second (A2, n = 39), third (A3, n = 24), and fourth (A4, n = 30) order according to their relative location in the network. No changes in A2 and A3 diameters were noted in either group. A4 diameters remained unchanged in groups C and Iso, whereas a significant reduction was found in group Hal at 0.75 and 1 MAC exposure (P < 0.05 compared with baseline and with groups C and Iso, respectively). During Iso exposure, functional capillary density was not significantly different when compared with baseline and group C, whereas in group Hal it decreased significantly at 0.5, 0.75, and 1 MAC, amounting to 61.1 +/- 9, 30.7 +/- 10.3, and 22.8 +/- 6.3%, respectively, of baseline (P < 0.01 vs. baseline and P < 0.05 vs. groups Iso and C for 0.75 and 1 MAC).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Impairment of Functional Capillary Density but Not Oxygen Delivery in the Hamster Window Chamber during Severe Experimental Malaria

2007 ◽  
Vol 170 (2) ◽  
pp. 505-517 ◽  
Author(s):  
Judith Martini ◽  
Irene Gramaglia ◽  
Marcos Intaglietta ◽  
Henri C. van der Heyde
Keyword(s):  
Oxygen Delivery ◽  
Capillary Density ◽  
Functional Capillary Density ◽  
Window Chamber

scholarly journals Increased hemoglobin O2 affinity protects during acute hypoxia

2012 ◽  
Vol 303 (3) ◽  
pp. H271-H281 ◽  
Author(s):  
Ozlem Yalcin ◽  
Pedro Cabrales
Keyword(s):  
Blood Flow ◽  
Acute Hypoxia ◽  
Severe Hypoxia ◽  
Microvascular Blood Flow ◽  
Vehicle Group ◽  
Control Group ◽  
Arterial Blood ◽  
Partial Pressures ◽  
Chamber Model ◽  
Window Chamber

Acclimatization to hypoxia requires time to complete the adaptation mechanisms that influence oxygen (O2) transport and O2 utilization. Although decreasing hemoglobin (Hb) O2 affinity would favor the release of O2 to the tissues, increasing Hb O2 affinity would augment arterial O2 saturation during hypoxia. This study was designed to test the hypothesis that pharmacologically increasing the Hb O2 affinity will augment O2 transport during severe hypoxia (10 and 5% inspired O2) compared with normal Hb O2 affinity. RBC Hb O2 affinity was increased by infusion of 20 mg/kg of 5-hydroxymethyl-2-furfural (5HMF). Control animals received only the vehicle. The effects of increasing Hb O2 affinity were studied in the hamster window chamber model, in terms of systemic and microvascular hemodynamics and partial pressures of O2 (Po2). Pimonidazole binding to hypoxic areas of mice heart and brain was also studied. 5HMF decreased the Po2 at which the Hb is 50% saturated with O2 by 12.6 mmHg. During 10 and 5% O2 hypoxia, 5HMF increased arterial blood O2 saturation by 35 and 48% from the vehicle group, respectively. During 5% O2 hypoxia, blood pressure and heart rate were 58 and 30% higher for 5HMF compared with the vehicle. In addition, 5HMF preserved microvascular blood flow, whereas blood flow decreased to 40% of baseline in the vehicle group. Consequently, perivascular Po2 was three times higher in the 5HMF group compared with the control group at 5% O2 hypoxia. 5HMF also reduced heart and brain hypoxic areas in mice. Therefore, increased Hb O2 affinity resulted in hemodynamics and oxygenation benefits during severe hypoxia. This acute acclimatization process may have implications in survival during severe environmental hypoxia when logistic constraints prevent chronic acclimatization.

Effects of erythrocyte flexibility on microvascular perfusion and oxygenation during acute anemia

2007 ◽  
Vol 293 (2) ◽  
pp. H1206-H1215 ◽  
Author(s):  
Pedro Cabrales
Keyword(s):  
Exchange Transfusion ◽  
Capillary Density ◽  
Microvascular Perfusion ◽  
Capillary Perfusion ◽  
Noninvasive Methods ◽  
Isovolemic Hemodilution ◽  
Rbc Membrane ◽  
Arterial Blood ◽  
Glutaraldehyde Solution ◽  
Fresh Rbcs

Responses to exchange transfusion using red blood cells (RBCs) with normal and reduced flexibility were studied in the hamster window chamber model during acute moderate isovolemic hemodilution to determine the role of RBC membrane stiffness in microvascular perfusion and tissue oxygenation. Erythrocyte stiffness was increased by 30-min incubation in 0.02% glutaraldehyde solution, and unreacted glutaraldehyde was completely removed. Filtration pressure through 5-μm pore size filters was used to quantify stiffness of the RBCs. Anemic conditions were induced by two isovolemic hemodilution steps using 6% 70-kDa dextran to a hematocrit (Hct) of 18% (moderate hemodilution). The protocol continued with an exchange transfusion to reduce native RBCs to 75% of baseline (11% Hct) with either fresh RBCs (RBC group) or reduced-flexibility RBCs (GRBC group) suspended in 5% albumin at 18% Hct; a plasma expander (6% 70-kDa dextran; Dex70 group) was used as control. Systemic parameters, microvascular perfusion, capillary perfusion [functional capillary density (FCD)], and oxygen levels across the microvascular network were measured by noninvasive methods. RBC deformability for GRBCs was significantly decreased compared with RBCs and moderate hemodilution conditions. The GRBC group had a greater mean arterial blood pressure (MAP) than the RBC and Dex70 groups. FCD was substantially higher for RBC (0.81 ± 0.07 of baseline) vs. GRBC (0.32 ± 0.10 of baseline) and Dex70 (0.38 ± 0.10 of baseline) groups. Microvascular tissue Po2 was significantly lower for Dex70 and GRBC vs. RBC groups and the moderate hemodilution condition. Results were attributed to decreased oxygen uploading in the lungs and obstruction of tissue capillaries by rigidified RBCs, indicating that the effects impairing RBC flexibility are magnified at the microvascular level, where perfusion and oxygenation may define transfusion outcome.

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