Adenosine Diphosphate In Blood Research Articles

Gravity sedimentation reveals functionally and morphologically different platelets in human blood

In contrast to red blood cells, platelets float rather than sediment when a column of blood is placed in the gravitational field. By the analogy of erythrocyte sedimentation (ESR), it can be expressed with the platelet antisedimentation rate (PAR), which quantitates the difference in platelet count between the upper and lower halves of the blood column after 1 h of 1 g sedimentation. Venous blood samples from 21 healthy subjects were analyzed for PAR. After a 1-h sedimentation, the upper and lower fractions of blood samples were analyzed for platelet count, mean platelet volume (MPV), immature platelet fraction (IPF), and high-fluorescence IPF (H-IPF). The mechanisms behind platelet flotation were explored by further partitioning of the blood column, time-dependent measurements of platelet count and comparison with ESR. The structure and function of the platelets were assessed by electron microscopy (EM) and atomic force microscopy (AFM), and platelet aggregometry, respectively. Platelet antisedimentation is driven by density differences and facilitated by a size-exclusion mechanism caused by progressive erythrocyte sedimentation. The area under the curve (AUC) of the whole blood adenosine diphosphate (ADP) aggregation curves showed significant differences between the upper and lower samples (p < .005). AUC in the upper samples of 38% of healthy subjects exceeded the top of the normal range (53–122) suggesting that ascending platelets show an intensified ADP-induced aggregability ex vivo. H-IPF was significantly higher in the upper samples (p < .05). EM and AFM revealed that platelets in the upper samples were larger in volume and contained 1.6 times more alpha granules compared to platelets in the lower samples. Our results indicate that antisedimentation is able to differentiate platelet populations based on their structural and functional properties. Therefore, PAR may be a suitable laboratory parameter in various thromboinflammatory disorders.

Changing of ATP and Its Metabolites in Blood Samples for Post Mortem Interval: In Vitro Study

Background: Postmortem interval (PMI) is an important in forensic practice. Many studies in blood and tissue ofanimals have revealed correlation between adenosine triphosphate (ATP) level and PMI. In this study aimed toexplore the correlation between human blood ATP and its metabolites level and PMI in vitro model.Methods: Ten milliliter of venous blood samples were collected form four healthy men and contained in EDTAtube. One milliliter of the blood sample was divided at 0, 1, 2, 4, 8, 12 and 24 h, respectively. The blood sampleswere extracted and measured ATP, adenosine diphosphate (ADP) and adenosine monophosphate (AMP) level byHigh performance liquid chromatography- diode array. Energy charge value was calculated to predict charge ofATP metabolites.Results: The blood ATP, ADP and AMP levels increased in the first hour. The blood ATP, ADP and AMP levelsdid not obviously change before 12 hour. The blood ATP level trended to decrease but the blood ADP and AMPlevels trended to increase after 24 hour. Energy Charge was not change in first 12 hour but trended to decreaseafter 24 hour.Conclusion: The blood ATP level and its metabolites changed after 12 hour and apply for the PMI investigation.

Effect of Exercise Training and Weight Loss on Platelet Reactivity in Overweight Patients With Coronary Artery Disease

Obesity is associated with increased platelet reactivity. Greater platelet reactivity presages adverse events in patients with coronary artery disease (CAD). We investigated whether exercise training and weight loss reduce platelet reactivity in overweight subjects with CAD. Study subjects (N = 46) were enrolled in a prospective randomized study of exercise training and behavioral weight loss, which contrasted the amount of exercise performed (750 vs. >3000 kcal/week). Platelet reactivity was assessed with the use of flow cytometry as the percentage of platelets expressing P-selectin or capable of binding fibrinogen in response to 1 μM adenosine diphosphate in blood before and after a 4-month program of exercise and behavioral weight loss. Markers of inflammation (high-sensitivity C-reactive protein), procoagulant activity (tissue plasminogen activator, plasminogen activator inhibitor 1), insulin sensitivity, body composition, physical activity, and fitness were also recorded. Platelet reactivity as assessed by P-selectin expression was decreased after exercise training and weight loss in study participants (from 34 ± 17% to 29 ± 17%; P = .01). The decrease was more pronounced in women (by 13% vs. 2% in men; P < .01). The change in platelet reactivity was not independently associated with measures of body composition or fitness. After controlling for exercise group and gender, the change in platelet reactivity was associated with changes in high-sensitivity C-reactive protein (r = 0.46) and insulin sensitivity (r = 0.46). In overweight patients with CAD, exercise training and weight loss are associated with a decrease in platelet reactivity that may predict an improved prognosis.

Treatment of Mitochondrial Encephalomyopathies With a Xanthine Oxidase Inhibitor

Five females with mitochondrial encephalomyopathies were treated for 3 to 7 years with a xanthine oxidase inhibitor (allopurinol, oral route, 20 mg/kg/day, in 2 or 3 doses daily). Clinical course was monitored in all patients. In addition, various metabolic variables, namely blood lactic acid, blood adenosine triphosphate, adenosine diphosphate, and adenosine monophosphate were monitored, as well as energy charge. Data obtained were compared with data for an age-matched control group of 10 healthy children. Four of the five patients manifested clinical improvement, and the remaining patient exhibited slower disease progression. Three of the four patients who exhibited clinical improvement also had normalization of blood lactic acid level. All five patients had an increase in blood adenosine triphosphate levels and a decline in blood adenosine monophosphate; four of the five manifested a decline in blood adenosine diphosphate and increased energy charge. Mean blood adenosine triphosphate was significantly increased with respect to pretreatment levels and with respect to the control group; mean energy charge displayed an increase, though this was not statistically significant. In one patient, reduction of the allopurinol dose to 10 mg/kg/day was followed by a decline in both blood adenosine triphosphate level and energy charge, and by clinical worsening. In conclusion, the xanthine oxidase inhibitor allopurinol appears to have had beneficial effects in these patients in terms of both energy metabolism and clinical course.

Adenine nucleotide metabolism in human blood – important roles for leukocytes and erythrocytes

Adenosine diphosphate (ADP) released into blood induces platelet aggregation and contributes to hemostasis and thrombosis. Released ATP can also induce platelet aggregation and there is evidence that blood leukocytes and also erythrocytes play important roles in this. Rapid metabolism of ADP and ATP by endothelial cells is important in protecting platelets from their effects. Here we have performed a systematic investigation of adenine nucleotide metabolism in human blood and the involvement of blood cells. Conversion of ATP to ADP in blood was due almost exclusively to the presence of leukocytes; plasma, platelets and erythrocytes made little or no contribution. Mononuclear leukocytes (MNLs) and polymorphonuclear leukocytes (PMNLs) were equally effective. Conversion of ADP to AMP was also promoted by leukocytes, with no involvement of platelets or erythrocytes. Some ADP was also converted to ATP in blood, apparently via an enzyme present in plasma, but ATP was then rapidly removed by the leukocytes. Conversion of AMP to adenosine occurred via a plasma enzyme with little or no contribution from any cellular element. As expected, in blood the adenosine produced was removed very rapidly by erythrocytes and then converted to inosine and then hypoxanthine. In the absence of erythrocytes plasma supported only a slow conversion of adenosine to inosine and hypoxanthine, which was not influenced by platelets or leukocytes. This study has demonstrated that leukocytes and erythrocytes play a major role in adenine nucleotide metabolism in blood and that these cells, as well as endothelial cells, may be important determinants of the effects of ATP and ADP on platelets.

Platelet aggregation in whole blood is a paradoxical predictor of ischaemic stroke: Caerphilly Prospective Study revisited

The Caerphilly Prospective Study demonstrates a paradoxical association of increased ischaemic stroke risk with decreased whole blood adenosine diphosphate (ADP) induced platelet sensitivity. A reanalysis of this association examines whether other haematological indices and prevalent disease at baseline may explain this finding. There were 1506 men free of clinical cardiovascular disease at baseline, with 85 men manifesting a first ischaemic stroke event over 8.3 years of follow-up in this population-based prospective cohort study. Using two different approaches, the paradoxical findings are confirmed and associations are slightly stronger after accounting for red cell, platelet, and white cell indices. A U-shaped relation of stroke with platelet count is noted. These findings are consistent with the existence of sub-clinical endothelial disease and compensatory mechanisms down-regulating ADP-induced aggregation sensitivity. They support an allostasis model of causality for understanding the paradox. A public health approach to prevention could have measurable impact if intervention strategies can be developed to alter early stages of disease appropriate to such mechanisms of causation.

Role of metabolism in pathogenesis of bacteremia due to Diplococcus pneumoniae in rabbits.

Since the lethal factors in most bacterial infections have not been defined, the role of metabolic alterations was investigated. Bacteremia was produced in rabbits by infection with Diplococcus pneumoniae, and the animals were grouped by severity of the disease as determined by progressive increments in the level of bacteremia, concentration of lactate in whole blood, and change in body temperature. Adenosine triphosphate and adenosine diphosphate in blood, liver, heart, and skeletal muscle were normal. Hepatic glycogen was variably decreased, and 45% of the animals were hypoglycemic despite normal hepatic glucogenesis. Concentrations of lactate in heart and liver increased. In-vitro oxidation of glucose, acetate, and pyruvate decreased in liver only. Glycolysis was normal in liver, heart, and muscle, but it was markedly increased in the lung. Hepatic synthesis of the triglyceride from acetate increased markedly. Hepatic microsomal protein synthesis apparently was normal, but amino acids in plasma, liver and skeletal muscle were increased. Complex multifaceted alterations in metabolism occurred. It is doubtful that anyone of these could be responsible for death, but the role played by these changes as a whole is unknown.

A Study of Factors Influencing the Enzymatic Elimination of Adenosine Diphosphate in Blood

SummaryThe red cells carry by far the greater part of the enzyme systems capable of eliminating adenosine diphosphate found in the blood but this activity is more concentrated in the platelets.These “ADPase” systems are strikingly stimulated by divalent cations with Mg++ being the most effective ion. Ca++, while possessing some effect, is antagonistic to Mg++ in the platelet system.A heat stable enhancing factor for the platelet “ADPase” system was shown to be present in platelet poor plasma. This factor was ineffective in preparations obtained from erythrocytes.