Rhys Christy

Immune and hemorheological changes in Chronic Fatigue Syndrome

BackgroundChronic Fatigue Syndrome (CFS) is a multifactorial disorder that affects various physiological systems including immune and neurological systems. The immune system has been substantially examined in CFS with equivocal results, however, little is known about the role of neutrophils and natural killer (NK) phenotypes in the pathomechanism of this disorder. Additionally the role of erythrocyte rheological characteristics in CFS has not been fully expounded. The objective of this present study was to determine deficiencies in lymphocyte function and erythrocyte rheology in CFS patients.MethodsFlow cytometric measurements were performed for neutrophil function, lymphocyte numbers, NK phenotypes (CD56dimCD16+ and CD56brightCD16-) and NK cytotoxic activity. Erythrocyte aggregation, deformability and fibrinogen levels were also assessed.ResultsCFS patients (n = 10) had significant decreases in neutrophil respiratory burst, NK cytotoxic activity and CD56brightCD16- NK phenotypes in comparison to healthy controls (n = 10). However, hemorheological characteristic, aggregation, deformability, fibrinogen, lymphocyte numbers and CD56dimCD16+ NK cells were similar between the two groups.ConclusionThese results indicate immune dysfunction as potential contributors to the mechanism of CFS, as indicated by decreases in neutrophil respiratory burst, NK cell activity and NK phenotypes. Thus, immune cell function and phenotypes may be important diagnostic markers for CFS. The absence of rheological changes may indicate no abnormalities in erythrocytes of CFS patients.

Heart rate variability is related to impaired haemorheology in older women with type 2 diabetes

Impaired heart rate variability (HRV)and haemorheology are independently associated with cardiovascular disease and diabetic complications. The aim of the present study was to investigate the relationships between parameters of HRV,and red blood cell (RBC) aggregation and deformability, in older women with type 2 diabetes. Twenty women (age 69 ± 2 yr) with uncomplicated type 2 diabetes and twenty controls (age 69 ± 3 yr) participated in the study. Beat-to-beat cardiac (RR) intervals over 5 min were analysed for HRV parameters in the time and frequency domains. Blood was sampled for RBC deformability, as well as RBC aggregation in two suspending mediums: haematocrit adjusted plasma and 3% dextran 70. RBC aggregation was increased and HRV was impaired for those with type 2 diabetes when compared with control. RBC aggregation was negatively related to low frequency power of HRV, and was positively related to high frequency power of HRV, for subjects with type 2 diabetes. RBC deformability was positively related to HRV only for those with type 2 diabetes. Impaired haemorheology is associated with reduced HRV in older women with type 2 diabetes, suggesting changes in the microcirculation may result in impaired modulation of cardiac cycles.

Erythrocyte Aggregation and Neutrophil Function in an Aging Population

There are limited investigations which have examined the relationship between neutrophil activation and erythrocyte aggregation in older persons. The purpose of the present study was to investigate the relationship between neutrophil activation and erythrocyte aggregation (EA) in an aging population. Twenty-eight male and female subjects were allocated into one of four groups with 7 participants in each group (group 1, 20–29 years; group 2, 30–39 years; group 3, 40–49 years; group 4, 50–59 years). EA was determined using the Myrenne aggregometer. Neutrophil function (respiratory burst and phagocytic activity) was assessed using flow cytometry. EA was found to increase with age. An ANOVA showed a significant (p < 0.05) increase for EA in autologous plasma in group 4 compared to groups 1 and 2. An ANOVA and Pearson’s correlation showed that phagocytic activity decreased with age. Furthermore, a positive correlation between stimulated phagocytic activity and erythrocyte aggregability at low shear in 3% dextran-70 solution was observed. The current investigation suggests a decrease in neutrophil phagocytic activity with age and EA was increased with age. Additionally, the current study is novel as it suggests a possible relationship between neutrophil phagocytic activity and erythrocyte aggregability.

Assessment of the hemorheological profile of koala and echidna

Koala, a marsupial, and echidna, a monotreme, are mammals native to Australia. Blood viscosity (62.5-1250s(-1)), red blood cell (RBC) deformability, RBC aggregation, aggregability and surface charge, and hematological parameters were measured in blood samples from six koalas and six echidnas and compared to adult human blood. Koala had the largest RBC mean cell volume (107.7+/-2.6fl) compared to echidna (81.3+/-2.6fl) and humans (88.4+/-1.2fl). Echidna blood exhibited the highest viscosity over the entire range of shear rates. Echidna RBC were significantly less deformable than koala RBC but more deformable than human RBC. Echidna RBC had significantly lower aggregability (i.e., aggregation in standardized dextran medium) than koala or human RBC, while aggregation in autologous plasma was similar for the three species. Erythrocyte surface charge as indexed by RBC electrophoretic mobility was similar for human and echidna cells but was 40% lower for koala RBC. Data obtained during this preliminary study indicate that koala and echidna have distinct hemorheological characteristics; investigation of these properties may reveal patterns relevant to specific behavioral and physiological features of these animals.

Haemorheology of the eastern grey kangaroo and the Tasmanian devil

The blood of two Australian marsupials, the eastern grey kangaroo (Macropus giganteus) and the Tasmanian devil (Sarcophilus harrisii), has been reported to have greater oxygen-carrying capacity (i.e. haemoglobin content) when compared with that of placental mammals. We investigated whether alterations of blood rheological properties are associated with the increased oxygen-carrying capacity of these marsupials. Eastern grey kangaroos (n = 6) and Tasmanian devils (n = 4) were anaesthetised for blood sampling; human blood (n = 6) was also sampled for comparison. Laboratory measurements included blood and plasma viscosity, red blood cell (RBC) deformability, RBC aggregation and the intrinsic tendency of RBC to aggregate, RBC surface charge and haematological parameters. Scanning electron micrographs of RBC from each species provided morphological information. High-shear blood viscosity at native haematocrit was highest for the Tasmanian devil. When haematocrit was adjusted to 0.4 L L–1, lower-shear blood viscosity was highest for the eastern grey kangaroo. RBC deformability was greatly reduced for the Tasmanian devil. Eastern grey kangaroo blood had the highest RBC aggregation, whereas Tasmanian devil RBC did not aggregate. The surface charge of RBC for marsupials was ~15% lower than that of humans. The dependence of oxygen-delivery effectiveness on haemoglobin concentration (i.e. oxygen content) and blood viscosity was quantitated by calculating the haematocrit to blood viscosity ratio and was 15–25% lower for marsupials compared with humans. Our results suggest that environmental pressures since the marsupial–monotreme divergence have influenced the development of vastly different strategies to maintain a match between oxygen demand and delivery.

Circulating bone marrow derieved osteo-progenitors in vasculature contributes towards vascular calcification

[Extract] Vascular calcification is an important determinant of cardiovascular mortality. The mechanisms responsible for vascular calcification are controversial. It has been suggested that the bone marrow derived osteo-progenitor population may contribute to the development of arterial mineralization. Osteocalcin expressing mononuclear cells (OCN+ MNCs) have recently been demonstrated within the circulation of adults and shown to have ability to carry out mineralization both in vitro and within mice. The aim of this study was to assess the association of vascular calcification with circulating bone marrow derived osteo-progenitors and stem cell mobilizing cytokines in two mice models and a human patient cohort.