Daniel J. Cho

Hemorheological Disorders in Diabetes Mellitus

The objective of the present study is to review hemorheological disorders in diabetes mellitus. Several key hemorheological parameters, such as whole blood viscosity, erythrocyte deformability, and aggregation, are examined in the context of elevated blood glucose level in diabetes. The erythrocyte deformability is reduced, whereas its aggregation increases, both of which make whole blood more viscous compared to healthy individuals. The present paper explains how the increased blood viscosity adversely affects the microcirculation in diabetes, leading to microangiopathy.

Hemorheology and Microvascular Disorders

The present review presents basic concepts of blood rheology related to vascular diseases. Blood flow in large arteries is dominated by inertial forces exhibited at high flow velocities, while viscous forces (i.e., blood rheology) play an almost negligible role. When high flow velocity is compromised by sudden deceleration as at a bifurcation, endothelial cell dysfunction can occur along the outer wall of the bifurcation, initiating inflammatory gene expression and, through mechanotransduction, the cascade of events associated with atherosclerosis. In sharp contrast, the flow of blood in microvessels is dominated by viscous shear forces since the inertial forces are negligible due to low flow velocities. Shear stress is a critical parameter in microvascular flow, and a force-balance approach is proposed for determining microvascular shear stress, accounting for the low Reynolds numbers and the dominance of viscous forces over inertial forces. Accordingly, when the attractive forces between erythrocytes (represented by the yield stress of blood) are greater than the shear force produced by microvascular flow, tissue perfusion itself cannot be sustained, leading to capillary loss. The yield stress parameter is presented as a diagnostic candidate for future clinical research, specifically, as a fluid dynamic biomarker for microvascular disorders. The relation between the yield stress and diastolic blood viscosity (DBV) is described using the Casson model for viscosity, from which one may be able determine thresholds of DBV where the risk of microvascular disorders is high.

Endothelial shear stress and blood viscosity in peripheral arterial disease.

This review examines the emerging role of endothelial shear stress (ESS) and blood viscosity on the initiation and progression of atherosclerosis in peripheral arterial disease. Among the variables determining ESS, blood viscosity has to date been the most overlooked by clinical researchers. Blood viscosity is a laboratory assessment that is minimally invasive and modifiable using pharmacologic therapy as well as by hemodilution. Monitoring and controlling blood viscosity not only modulates ESS, but also reduces peripheral vascular resistance and increases blood flow to the lower extremities.

Influence of non-Newtonian viscosity of blood on microvascular impairment

The present research investigated the role of blood viscosity on flow within a microvascular network to identify the conditions of blood flow stagnation. When the yield stress of blood was less than 0.005 Pa, there were no stagnant regions in the microvasculature. However, when the yield stress increased to 0.05 Pa, stagnant or reduced flow areas began to appear, which grew and expanded rapidly with further increase in the yield stress. Thus, the yield stress determined from blood viscosity profile of a patient can be utilized to evaluate the risk of circulatory impairment.

Reduced amputation rate with isovolemic hemodilution in critical limb ischemia patients

AIMS Critical limb ischemia (CLI) patients are characterized by intractable pain in spite of medication, non-healing ulcers, and gangrene. The objective of this study was to investigate whether or not isovolemic hemodilution treatment can reduce the rate of major amputations in CLI. METHODS 28 patients were studied who had tissue loss on Rutherford Grade III, Category 5 or 6. The subjects were divided into two arms: standard-of-care, conventional therapy (CT) (n = 15) as a control group and hemodilution therapy (HT) (n = 13) as a study group. For the HT group, weekly isovolemic hemodilution was performed over 4 consecutive weeks, removing 250 ml of whole blood with the infusion of hydroxyl-ethyl starch solution. Blood viscosity, hematocrit, hemoglobin, ankle-brachial index, VA pain scale, time-to-amputation from admission, and survival time were measured. RESULTS The mean Hct gradually decreased from 36.6 to 35.1, whereas the WBV at a shear rate of 1 s-1 significantly decreased from 18.2 to 10.5 during the same period. Subsequently, tissue oxygen delivery index, defined as the ratio of Hct to WBV at a shear rate of 1 s-1, increased from 24.4 to 37.0 by 51.7%, suggesting improvements in oxygen delivery in the patients. The average rate of lower limb major amputation in the control group was 93% (14/15), whereas that in the study group was 31% (4/13) (p = 0.001). Amputation-free median survival time and amputation-free 5-year survival rate in the control group were 1.2 months and 7%, while those in the study group were 30.2 months and 44% (p = 0.001). There were no adverse effects from repetitive hemodilution in the study group. CONCLUSIONS Isovolemic hemodilution treatment of CLI patients was found to be well-tolerated and reduced the rate of major amputation resulting from the deterioration of CLI.

Reduction of low-density lipoprotein cholesterol, plasma viscosity, and whole blood viscosity by the application of pulsed corona discharges and filtration

The present study investigated the feasibility of applying pulsed corona discharges to blood plasma to reduce the viscosity of blood plasma and whole blood. Blood plasma was separated from blood cells, treated with corona discharges, and filtered before it was re-mixed with blood cells. Plasma viscosity (PV), whole blood viscosity (WBV), and low-density lipoprotein (LDL)-c concentration were measured before and after the corona treatment and filtration. Both PV and WBV increased in the case of the corona treatment only, whereas both of them decreased in the case of the corona treatment plus filtration. In particular, the LDL-c decreased in the case of the corona treatment plus filtration by 31.5% from the baseline value. The effect of the corona treatment on the reduction of the WBV was significant at low shear rates, but not at high shear rates, suggesting that the precipitation of the molecules in blood plasma by the corona treatment and subsequent removal may suppress the aggregation of erythrocytes and improve rheological properties of blood.

Ticagrelor and the Prevention of Microvascular Complications in Diabetes Patients with Lower Extremity Arterial Disease; Rationale and Design of the Hema-Kinesis Trial

BackgroundLower extremity arterial disease (LEAD) occurs more common in patients with diabetes than without diabetes. Microvascular complications of diabetes contribute to higher rates of adverse limb events in patients with LEAD. Blood flow in the macrocirculation and microcirculation is reduced with increasing low-shear and high-shear blood viscosity. We hypothesize that the adenosine enhancing properties of ticagrelor will reduce low-shear blood viscosity and improve microcirculatory flow in the dorsum of the feet of patients with type 2 diabetes. Ticagrelor is a P2Y12 receptor antagonist with evidence of cardiovascular event reduction in patients with acute coronary syndromes and those with a previous myocardial infarction. In a large multicenter trial of patients with symptomatic LEAD and a history of limb revascularization, ticagrelor was no more effective than clopidogrel in reducing cardiovascular disease events; however, this trial was not designed to investigate microvascular complications of diabetes.DesignHema-kinesis will evaluate whether ticagrelor monotherapy or ticagrelor combined with aspirin as compared with aspirin monotherapy can reduce blood viscosity-dependent blood flow in the feet of type 2 diabetes patients with LEAD. Eligible study participants will be randomized into a three-arm double-dummy crossover trial design. All subjects will have baseline blood viscosity measurements and determinations of microvascular flow using laser Doppler flowmetry.SummaryIf the results of Hema-kinesis are positive, ticagrelor should be considered as treatment to reduce microvascular complications of LEAD in patients with type 2 diabetes.

Stretched arc discharge in produced water

The objective of the present study was to investigate the feasibility of stretching an arc discharge in produced water to increase the volume of produced water treated by plasma. Produced water is the wastewater generated by hydraulic fracturing of shale during the production phase in shale-oil or shale-gas exploration. The electric conductivity of produced water is in the range of 50-200 mS/cm, which provides both a challenge and opportunity for the application of plasmas. Stretching of an arc discharge in produced water was accomplished using a ground electrode and two high-voltage electrodes: one positioned close to the ground electrode and the other positioned farther away from the ground. The benefit of stretching the arc is that the contact between the arc and water is significantly increased, resulting in more efficient plasma treatment in both performance and energy cost.