Dr. Ron’s Research Review – July 11, 2012

This week’s research review focuses on Blood Viscosity.

Review Articles

Blood viscosity modulates tissue perfusion. (Lenz, Rebel et al. 2008)

The role of wall shear in atherosclerosis. (Caro 2009)

Blood viscosity at different stages of diabetes (Richards and Nwose 2010)

Nitric Oxide

Vascular aging and cardiovascular disease are both associated with endothelial dysfunction, or a marked decrease in production and bioavailability the vasodilator of nitric oxide (NO). As a result of decreased nitric oxide availability, aging vessels often exhibit endothelial cell senescence and increased oxidative stress. One of the most potent activators of NO production is fluid shear stress produced by blood flow. (Collins and Tzima 2011)

Phosphatidylserine

Basal levels of phosphatidylserine are required to activate survival pathways in endothelial cells and thereby contribute to the overall protective mechanism initiated by shear stress. (Freed, Shortreed et al. 2008)

Cigarette Smoking

High blood viscosity is closely associated with cigarette smoking and markedly reduced by smoking cessation. (Shimada, Hasegawa et al. 2011)

Earthing

Earthing (Grounding) the Human Body Reduces Blood Viscosity (Chevalier, Sinatra et al. 2012)

Dr. Ron


Articles

Discovery of the role of wall shear in atherosclerosis

            (Caro 2009) Download

The suggestion was made in the 1870s that mechanical irritation of the arterial wall is a cause of atherosclerosis, because the changes were chiefly found at points "exposed to the full stress and impact of the blood." The mechanical damage theory persisted until well into the 20th century when, with interest increasing in multidisciplinary research, two fluid mechanical proposals were advanced for the patchy distribution of the lesions. One advocated high- and the other low-wall shear. Arterial wall shear stress levels appeared, however, insufficiently high to damage the endothelium. In contrast, examination of cadaver human arteries, combined with flow studies in models and casts of arteries, implied that the lesions occurred preferentially in regions expected to experience low-wall shear; a mechanism, involving arterial wall lipid metabolism and shear-dependent blood-wall mass transport, was suggested to account for that distribution. These proposals helped stimulate extensive investigation of arterial fluid mechanics/mass transport and vascular biology/pathology, revealing mechanisms that may explain the now widely confirmed preferred occurrence of atherosclerosis in low wall shear regions in adult human beings.

Earthing (Grounding) the Human Body Reduces Blood Viscosity-a Major Factor in Cardiovascular Disease

            (Chevalier, Sinatra et al. 2012) Download

Abstract Objectives: Emerging research is revealing that direct physical contact of the human body with the surface of the earth (grounding or earthing) has intriguing effects on human physiology and health, including beneficial effects on various cardiovascular risk factors. This study examined effects of 2 hours of grounding on the electrical charge (zeta potential) on red blood cells (RBCs) and the effects on the extent of RBC clumping. Design/interventions: Subjects were grounded with conductive patches on the soles of their feet and palms of their hands. Wires connected the patches to a stainless-steel rod inserted in the earth outdoors. Small fingertip pinprick blood samples were placed on microscope slides and an electric field was applied to them. Electrophoretic mobility of the RBCs was determined by measuring terminal velocities of the cells in video recordings taken through a microscope. RBC aggregation was measured by counting the numbers of clustered cells in each sample. Settings/location: Each subject sat in a comfortable reclining chair in a soundproof experiment room with the lights dimmed or off. Subjects: Ten (10) healthy adult subjects were recruited by word-of-mouth. Results: Earthing or grounding increased zeta potentials in all samples by an average of 2.70 and significantly reduced RBC aggregation. Conclusions: Grounding increases the surface charge on RBCs and thereby reduces blood viscosity and clumping. Grounding appears to be one of the simplest and yet most profound interventions for helping reduce cardiovascular risk and cardiovascular events.

Hemodynamic forces in endothelial dysfunction and vascular aging

         (Collins and Tzima 2011) Download

Aging is a key risk factor associated with the onset of cardiovascular disease. Notably, vascular aging and cardiovascular disease are both associated with endothelial dysfunction, or a marked decrease in production and bioavailability the vasodilator of nitric oxide (NO). As a result of decreased nitric oxide availability, aging vessels often exhibit endothelial cell senescence and increased oxidative stress. One of the most potent activators of NO production is fluid shear stress produced by blood flow. Interestingly, age-related decrease in NO production partially results from endothelial insensitivity to shear stress. While the endothelial cell response to fluid shear stress has been well characterized in recent years, the exact mechanisms of how the mechanical force of fluid shear stress is converted into intracellular biochemical signals are relatively unknown. Therefore, gaining a better knowledge of mechanosignaling events in endothelial cells may prove to be beneficial for developing potential therapies for cardiovascular diseases.

Revealing the role of phosphatidylserine in shear stress-mediated protection in endothelial cells

         (Freed, Shortreed et al. 2008) Download

Previous studies have demonstrated that endothelial cells exposed to laminar shear stress are protected from apoptotic stimuli such as tumor necrosis factor (TNF)-alpha. The authors investigated the role of phosphatidylserine (PS) in this phenomenon. Western blot analysis of cleaved caspase 3 was used as an indicator of apoptosis and revealed that in the absence of serine, endothelial cells exposed to laminar shear stress were unable to protect against TNF-alpha-induced apoptosis, in contrast to sheared cells grown in regular medium. It was also found that shear-induced activation of the Akt pathway was significantly decreased in cells grown without serine. In addition, quantitation of PS using a novel isotopic labeling technique involving the use of formalin revealed that stearoyl-oleic PS (18:0/18:1) did not increase during shear treatment. These findings suggest that basal levels of PS are required to activate survival pathways in endothelial cells and thereby contribute to the overall protective mechanism initiated by shear stress.

Blood viscosity modulates tissue perfusion: sometimes and somewhere

            (Lenz, Rebel et al. 2008) Download

Each organ possesses specific properties for controlling microvascular perfusion. Such specificity provides an opportunity to design transfusion fluids that target thrombo-embolic or vasospasm-induced ischemia in a particular organ or that optimize overall perfusion from systemic shock. The role of viscosity in the design of these fluids might be underestimated, because viscosity is rarely monitored or considered in critical care decisions. Studies linking viscosity-dependent changes of microvascular perfusion to outcome-relevant data suggest that whole blood viscosity is negligible as a determinant of microvascular perfusion under physiological conditions when autoregulation is effective. Because autoregulation is driven to maintain oxygen supply constant, the organism will compensate for changes in blood viscosity to sustain oxygen delivery. In contrast, under pathological conditions in the brain and elsewhere, increases of overall viscosity should be avoided - including all the situations where vascular autoregulatory mechanisms are inoperative due to ischemia, structural damage or physiologic dysfunction. As latter conditions are not to identify with high certainty, the risks that accompany therapeutic correction of blood viscosity are outweighing the benefits. The ability to bedside monitor blood viscosity and to link changes in viscosity to outcome parameters in various clinical conditions would provide more solid foundation for evidence-based clinical management.

Blood viscosity at different stages of diabetes pathogenesis

            (Richards and Nwose 2010) Download

Hyperglycaemia-induced oxidative stress is implicated as a cause of increased whole blood viscosity (WBV), which is a clinically modifiable risk factor for cardiovascular disease (CVD). However, whether or not there is variation in WBV at different stages of diabetes mellitus (DM) has yet to be confirmed. The sensitivity of underlying oxidative stress has also yet to be investigated. A total of 154 participants representing different stages of DM pathogenesis were selected for the study. Healthy control, prediabetes, DM and DM+CVD groups were compared for variation in WBV levels. The prevalence of oxidative stress, indicated by abnormal levels of erythrocyte glutathione, malondialdehyde and methaemoglobin, associated with high WBV was evaluated. The results showed a statistically significant difference in WBV between groups (P < 0.03). The level of viscosity was significantly lower in the control group relative to the prediabetes group (P < 0.01) and DM+CVD group (P < 0.04). There was no statistically significant difference between the DM+CVD and prediabetes groups. Greater than 76% prevalence of oxidative stress was shown to be associated with high WBV, reaching 95% prevalence in prediabetes. The study showed that WBV varies between individuals with different stages of diabetic macrovascular pathogenesis, including prediabetes. Redefining the criteria for use of WBV on the basis of sensitivity to underlying oxidative stress, rather than specificity to a disease condition, means that this easily performed test is an option to consider in an all-inclusive laboratory approach to early intervention against future diabetic macrovascular complications. This is particularly important for individuals with subclinical hyperglycaemia.

High blood viscosity is closely associated with cigarette smoking and markedly reduced by smoking cessation.

         (Shimada, Hasegawa et al. 2011) Download

BACKGROUND: Cigarette smoking is an independent risk factor for cardiovascular events such as myocardial infarction and stroke. To date, a useful and convenient method of predicting such events in smokers has not been established. The rheological properties of blood assessed by the microchannel method reflect the blood's viscosity and the state of microthrombus formation, which may predict cardiovascular thrombotic events. METHODS AND RESULTS: Blood fluidity was assessed in 74 smoking patients (54 men, 20 women, mean age 57.9 years) by measuring the blood passage time (BPT) in an aliquot (100 microl) of blood using the Micro Channel Array Flow Analyzer. BPT was significantly related with smoking variables such as daily consumption of tobacco (r = 0.236, P = 0.044), Brinkman's index (r = 0.252, P = 0.033), the Fagerstrom Test for Nicotine Dependence (r = 0.257, P = 0.029), and the score of a self-rating depression scale (r = 0.236, P < 0.05). Multivariate regression analysis revealed that an independent BPT determinant was daily consumption of tobacco (r = 0.326, P = 0.045). Furthermore, smoking cessation markedly decreased BPT from 63.0 s to 49.7 s (P = 0.002) at 3 months after the start of therapy. CONCLUSIONS: Unfavorable blood rheology is closely associated with cigarette smoking and may reflect increased cardiovascular risk in smokers. The study results also suggest that such risk can be reduced after only 3 months of smoking cessation.


References

Caro, C. G. (2009). "Discovery of the role of wall shear in atherosclerosis." Arterioscler Thromb Vasc Biol 29(2): 158-61.

Chevalier, G., S. T. Sinatra, et al. (2012). "Earthing (Grounding) the Human Body Reduces Blood Viscosity-a Major Factor in Cardiovascular Disease." J Altern Complement Med.

Collins, C. and E. Tzima (2011). "Hemodynamic forces in endothelial dysfunction and vascular aging." Exp Gerontol 46(2-3): 185-8.

Freed, J. K., M. R. Shortreed, et al. (2008). "Revealing the role of phosphatidylserine in shear stress-mediated protection in endothelial cells." Endothelium 15(4): 225-30.

Lenz, C., A. Rebel, et al. (2008). "Blood viscosity modulates tissue perfusion: sometimes and somewhere." Transfus Altern Transfus Med 9(4): 265-272.

Richards, R. S. and E. U. Nwose (2010). "Blood viscosity at different stages of diabetes pathogenesis." Br J Biomed Sci 67(2): 67-70.

Shimada, S., K. Hasegawa, et al. (2011). "High blood viscosity is closely associated with cigarette smoking and markedly reduced by smoking cessation." Circ J 75(1): 185-9.