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

La Jolla Bioengineering Institute, 505 Coast Blvd. South, La Jolla, CA 92037, USA.
AJP Heart and Circulatory Physiology (Impact Factor: 3.84). 12/2006; 291(5):H2445-52. DOI: 10.1152/ajpheart.00394.2006
Source: PubMed


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.

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    • "Increasing plasma viscosity with viscogenic plasma expanders provide positive effects on microvascular function in an acute hemorrhagic shock and an extreme hemodilution in unanesthetized animal models.[12345] High-viscogenic plasma expanders (HVPE) improve capillary perfusion and sustain arterial blood pressure compared to low-viscogenic plasma expanders (LVPE) after resuscitation from hemorrhagic shock and continuous bleeding.[6] "
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    ABSTRACT: Background: Endothelial nitric oxide synthase (eNOS) is generally expressed in endocardial cells, vascular endothelial cells and ventricular myocytes. However, there is no experimental study elucidating the relationship between cardiac eNOS expression and elevated plasma viscosity in low oxygen delivery pathological conditions such as hemorrhagic shock-resuscitation and hemodilution. This study tested the hypothesis that elevated plasma viscosity increases cardiac eNOS expression in a hemodilution model, leading to positive effects on cardiac performance. Materials and Methods: Two groups of golden Syrian hamster underwent an acute isovolemic hemodilution where 40% of blood volume was exchanged with 2% (low-viscogenic plasma expander [LVPE]) or 6% (high-viscogenic plasma expander [HVPE]) of dextran 2000 kDa. In control group, experiment was performed without hemodilution. All groups were performed in awake condition. Experimental parameters, i.e., mean arterial blood pressure (MAP), heart rate, hematocrit, blood gas content and viscosity, were measured. The eNOS expression was evaluated by eNOS Western blot analysis. Results: After hemodilution, MAP decreased to 72% and 93% of baseline in the LVPE and HVPE, respectively. Furthermore, pO2 in the LVPE group increased highest among the groups. Plasma viscosity in the HVPE group was significantly higher than that in control and LVPE groups. The expression of eNOS in the HVPE group showed higher intensity compared to other groups, especially compared with the control group. Conclusion: Our results demonstrated that cardiac eNOS has responded to plasma viscosity modulation with HVPE and LVPE. This particularly supports the previous studies that revealed the positive effects on cardiac function in animals hemodiluted with HVPE.
    Asian Journal of Transfusion Science 03/2014; 8(2):100-104. DOI:10.4103/0973-6247.137444
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    • "Similarly, Tsai et al.11) demonstrated that elevated plasma viscosity increased perivascular NO production in concert with the increased aortic eNOS protein expression during extreme hemodilution. Studies in awake animals treated with high viscosity plasma expanders (HVPEs) showed advantageous effects in the microvascular function in both hemorrhagic shock-resuscitation and acute extreme hemodilution models.12)13)14) These studies revealed that an elevated plasma viscosity positively correlates with increased WSS and NOS. "
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    ABSTRACT: Increased vascular wall shear stress by elevated plasma viscosity significantly enhances the endothelial nitric oxide synthase (eNOS) activity during an acute isovolemic hemodilution. Also the modulation of plasma viscosity has effects on the cardiac function that were revealed if a left ventricular (LV) pressure-volume (PV) measurement was used. The aim of this study was to assess cardiac function responses to nitric oxide synthase (NOS) inhibitors with the presence of an elevated plasma viscosity but a low hematocrit level. Furthermore, systemic parameters were monitored in a murine model. As test group five anesthetized hamsters were administered with N(G)-nitro-L-arginine methyl ester (L-NAME), NOS inhibitor, whereas five other hamsters were used as control group without L-NAME infusion. The dosage of L-NAME was 10 mg/kg. An isovolemic hemodilution was performed by 40% of estimated blood volume with 6% w/v dextran 2000 kDa, high viscosity plasma expanders (PEs) with viscosity 6.34 cP. LV function was measured and assessed using a 1.4 Fr PV conductance catheter. The study results demonstrated that NOS inhibition prevented the normal cardiac adaptive response after hemodilution. The endsystolic pressure increased 14% after L-NAME infusion and maintained higher than at the baseline after hemodilution, whereas it gradually decreased in the animals without L-NAME infusion. The admission of L-NAME significantly decreased the maximum rate of ventricular pressure rise (+dP/dtmax), stroke volume and cardiac output after hemodilution if compared to the control group (p<0.05). This finding supports the presumption that nitric oxide induced by an increased plasma viscosity with the use of a high viscosity PE plays a major role in the cardiac function during an acute isovolemic hemodilution.
    Korean Circulation Journal 03/2014; 44(2):105-12. DOI:10.4070/kcj.2014.44.2.105 · 0.75 Impact Factor
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    • "Plasma expander viscosity has been shown to influence FCD and local tissue perfusion during extreme hemodilution [33]. Increasing blood viscosity during hemodilution by using a high-viscosity plasma expander (6% dextran 500 kDa, 0.7% alginate) leads to better microvascular perfusion in comparison with using a low-viscosity plasma expander (6% dextran 70 kDa) [29,34,35]. The viscous drag exerted by plasma expanders is proposed to interact with the endothelium and trigger a vasodilator response. "
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    ABSTRACT: Preoperative hemodilution is an established practice that is applied to reduce surgical blood loss. It has been proposed that polyethylene glycol (PEG) surface decorated proteins such as PEG-conjugated human serum albumin may be used as non-oxygen-carrying plasma expanders. The purpose of this study was to determine whether there is any difference in survival time after severe hemorrhagic shock following extreme hemodilution using a conventional hydroxyethyl starch (HES)-based plasma expander or PEG-albumin. Experiments were performed using the hamster skinfold window preparation. Human serum albumin that was surface decorated with PEG was compared with Voluven 6% (Fresenius Kabi, Austria; a starch solution that is of low molecular weight and has a low degree of substitution; HES). These plasma expanders were used for a 50% (blood volume) exchange transfusion to simulate preoperative hemodilution. Exchange transfusion was followed by a 60% (blood volume) hemorrhage to reproduce a severe surgical bleed over a 1 hour period. Observation of the animal was continued for another hour during the shock phase. The PEG-albumin group exhibited significantly greater survival rate than did the HES group, in which none of the animals survived the hemorrhage phase of the experiment. Among the treatment groups there were no changes in mean arterial pressure and heart rate from baseline after hemodilution. Both groups experienced gradual increases in arterial oxygen tension and disturbance in acid-base balance, but this response was more pronounced in the HES group during the shock period. Mean arterial pressure remained elevated after the initial hemorrhage period in the PEG-albumin group but not in the HES group. Maintenance of a greater mean arterial pressure during the initial stages of hemorrhage is proposed to be in part due to the improved volume expansion with PEG-albumin, as indicated by the significant decrease in systemic hematocrit compared with the HES group. PEG-albumin treatment yielded higher functional capillary density during the initial stages of hemorrhage as compared with HES treatment. The ability of PEG-albumin to prolong maintenance of microvascular function better than HES is a finding that would be significant in a clinical setting involving preoperative blood management and extreme blood loss.
    Critical care (London, England) 02/2008; 12(2):R54. DOI:10.1186/cc6874 · 4.48 Impact Factor
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