Professor George B. Thurston discovered the viscoelasticity of blood and he was able to precisely measure viscoelasticity (viscosity and elasticity are the two numerical values) in the early 1970s.1–3 The viscoelasticity of blood is the intrinsic property governing flow throughout the circulatory system in response to pressure developed by the heart.1 Viscosity of blood has a primary influence on larger arteries, whereas the elasticity has primary influence in the arterioles and capillaries. Hematocrit, temperature, plasma viscosity, red cell deformability and aggregation tendency, and plasma composition all have a direct impact on the viscoelasticity of blood.4,5 After Prof. Thurston’s discovery, several investigators established direct links between viscoelasticity and many diseases, including coronary artery disease, myocardial infarction, stroke, and cerebrovascular disease.6–8
During the past several years, we have conducted clinical and animal experiments to investigate the impact of cardiopulmonary procedures on blood viscoelasticity.9–11 The objective of this study was to determine the changes in blood viscoelasticity during and after cardiopulmonary bypass (CPB) procedures in pediatric cardiac patients.
Patients and Methods
After Institutional Review Board approval, 12 pediatric cardiac patients, subjected to hypothermic (22–28°C) CPB procedures, were enrolled in this study. Arterial blood samples (1 ml each) were taken before CPB, on normothermic CPB, on hypothermic CPB, and 1 and 24 hours after CPB. Blood samples were collected before and after surgery directly from the patients by anesthesiologists. The remainder of the samples was collected from the arterial side of the heart-lung machine by perfusionists.
The test was completed in 3 minutes and required 1.0 ml anticoagulated blood. Blood samples were tested with the Vilastic-3 Viscoelasticity Analyzer (Vilastic Scientific, Inc., Austin, TX) at a frequency of 2 Hz and at 22°C for a range of shear strain from 0.1 to 10.0 in a cylindrical tube with a diameter of 1 mm. Before measurements began, the sample was allowed to rest for 30 seconds in the measurement tube, to allow the internal blood structures to reach a quiescent state. The measurements of viscoelasticity as a function of strain were analyzed at strains of 0.2 (quiescent aggregated state), 1.0 (the ultimate breakup of the aggregates), and 5.0 (cell deformation and layer formation).12
Analysis of variance with a complete block design including 12 replications was used to identify the statistical significance for all five experimental stages.
The average age was 33 months, with the youngest patient being 4 weeks and the oldest 7 years. Patients’ temperatures were 36.5°C ± 0.8°C before CPB, 35.6°C ± 1.2°C during normothermic CPB, 26.2°C ± 1.9°C during hypothermic CPB, 37.2°C ± 0.2°C 1 hour after CPB, and 36.8°C ± 0.2°C 24 hours after CPB. At the same experimental stages, hematocrit levels were 32.4% ± 3.4%, 24.2% ± 3.5%, 23.2% ± 3.8%, 28% ± 4.4%, and 33.4% ± 3.5%, respectively.
Viscoelasticity at a Strain of 0.2
Compared with the pre-CPB level (0.0579 ± 0.0109 Poise), the viscosity was significantly lower during normothermic CPB (0.0347 ± 0.009 Poise, p < 0.01), hypothermic CPB (0.0347 ± 0.01 Poise, p < 0.01), and 1 hour after CPB (0.0392 ± 0.008 Poise, p < 0.01). The viscosity was higher 24 hours after CPB (0.066 ± 0.013 Poise, p < 0.01) when compared with the pre-CPB level, but these results were not statistically significant.
Elasticity was also significantly altered during normothermic CPB, hypothermic CPB, 1 hour after CPB, and 24 hours after CPB compared with the pre-CPB levels. A detailed analysis of the viscoelasticity results is shown in Figure 1.
Viscoelasticity at a Strain of 1.0
Compared with the pre-CPB levels (0.0464 ± 0.007 Poise), the viscosity was significantly lower during normothermic CPB (0.0305 ± 0.006 Poise, p < 0.01), hypothermic CPB (0.03 ± 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0334 ± 0.006 Poise, p < 0.01). The viscosity at a strain of 1.0 24 hours after CPB (0.0525 ± 0.01 Poise, p = NS) was slightly higher than pre-CPB levels.
The elasticity at a strain of 1.0 was significantly altered during normothermic CPB (0.0016 ± 0.0007 Poise, p < 0.01), hypothermic CPB (0.0015 ± 0.0007 Poise, p < 0.01), and 1 hour after CPB (0.0017 ± 0.0005 Poise, p < 0.01) compared with the pre-CPB levels (0.0048 ± 0.0001 Poise). Elasticity 24 hours after CPB (0.0068 ± 0.003 Poise, p = 0.06) was significantly higher when compared with the pre-CPB level (0.0048 ± 0.0001 Poise). A summary of the viscoelasticity at a strain of 1 is shown in Figure 2.
Viscoelasticity at a Strain of 5.0
Viscoelasticity of blood at a strain of 5.0 was significantly altered during normothermic CPB, hypothermic CPB, and 1 and 24 hours after CPB compared with the pre-CPB levels. Figure 3 shows a detailed analysis of the viscoelasticity results at a strain of 5.0.
The viscoelasticity of blood was significantly altered during and after CPB procedures in pediatric patients. Although hematocrit and temperature are the two major factors that influence viscoelasticity of blood during in vitro experiments, the significant changes in viscoelasticity during open-heart procedures are multifactorial.9–11 In addition to the temperature and hematocrit, modes of perfusion (pulsatile and non-pulsatile), cardiotomy suction, design of membrane oxygenators, types of arterial pump (roller and centrifugal), and mechanical forces of the extracorporeal circuit may have a significant impact on blood viscoelasticity.9–11
Viscoelasticity at strains of 0.2, 1.0, and 5.0 were very similar during normothermic and hypothermic CPB. Although the hematocrit levels were very similar between normothermic and hypothermic CPB, the temperature was significantly lower in the hypothermic stage compared with the normothermic stage (26.2°C ± 1.9°C vs. 35.6°C ± 1.2°C). Therefore, temperature alone was not the cause of the significant effects seen in viscoelasticity during CPB procedures.
After 1 hour of CPB, the adverse effects of the CPB procedure were reflected in blood viscoelasticity. At this particular stage, both viscosity and elasticity were significantly lower when compared to the baseline levels. More interestingly, 24 hours after CPB, with very similar temperature and hematocrit levels, the viscoelasticity was higher at all strains as compared with the pre-CPB levels. These results also suggest that the significant changes in blood viscoelasticity during and after CPB cannot be explained solely with the changes in temperature and hematocrit.
To the best of our knowledge, these are the first results ever presented on blood viscoelasticity during and after pediatric CPB procedures. Viscosity and elasticity at strains of 0.2, 1.0, and 5.0 were significantly lower during normothermic and hypothermic CPB and 1 hour after CPB when compared with the pre-CPB level. The viscoelasticity of blood was higher 24 hours after CPB at all strains. Further investigation of the effects of hypothermic CPB on blood viscoelasticity and the outcomes of pediatric cardiac patients is warranted.
The author thanks Drs. Nancy Henderson and George B. Thurston for their technical assistance for viscoelasticity measurements.
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