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Biomedical subjects

J A Dormandy

Publications and source records attributed to J A Dormandy.

At least 73 records · Page 4Linked to original sources
PubMed1989

Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers.

The formation of dense, poorly deformable sickle cells was studied by subjecting pre-separated, less dense cells to repeated deoxygenation and reoxygenation for 15 h. In the presence of Ca (2 mmol/l), this process caused the number of irreversible sickled cells to increase five-fold, mean cell haemoglobin concentration to increase by 13% and cellular potassium to decrease by 22%. Also, red cell filterability through 5 microns filter pores was greatly worsened. These effects decreased but were not totally abolished when the extracellular Ca concentration was lowered to zero or 0.01 mmol/l. If a high K medium was used (135 mmol/l), cell swelling rather than shrinkage occurred. Swelling also occurred if ouabain was added to the incubation. The Ca-channel blockers nitrendipine and nisoldipine had different effects. Nitrendipine, in the range 10(-7) - 10(-5) mol/l, was partially protective against all the induced changes, but nisoldipine was not protective at 10(-8) or 10(-6) mol/l. Thus, deterioration in the properties of sickle cells appears to be linked to Ca-dependent potassium loss during repeated sickling and is inhibited by nitrendipine.

Anemia, Sickle Cell↗
PubMed1989

Changes in the flow properties of white blood cells after acute myocardial infarction.

Because they can obstruct blood vessels and release noxious substances, white blood cells may contribute to the development of tissue ischaemia. The flow properties of white cells were tested after myocardial infarction, by measuring the filtration rates of cell suspensions through 8 microns pore filters. Compared with mononuclear cells from age matched controls, mononuclear cells from patients with infarction showed impaired filterability within the first day after the onset of pain; this condition persisted for at least two days and by day 10 it was improved. On day 1, granulocyte filterability and the proportion showing morphological evidence of activation were nearly normal. By day 3 the flow resistance and activation had increased, but the changes seen depended on the age of the patient. The filterability and activation of granulocytes from patients aged less than 60 were significantly increased from day 1, whereas there were no changes in granulocytes from patients aged greater than 60 years. Suspensions of unfractionated white cells showed changes intermediate between the mononuclear cells and granulocytes. A group of five patients who presented with chest pain but who were subsequently found not to have had an infarction showed no evidence of abnormal filterability or activation. The changes in filterability probably reflect white cell activation, which may have an adverse effect on the perfusion of the ischaemic myocardium.

Adult↗
PubMed1989

Altered filtrability of white blood cells after myocardial infarction.

Abnormal white blood cell rheological behaviour has been implicated as a cause of blood flow disturbances under conditions of ischaemia and reduced perfusion pressure. Accordingly, we have tested the mechanical properties of white cells following myocardial infarction by measuring the rate at which suspension of these cells cause plugging of Nuclepore filters. The number of clogging particles in a standard white cell suspension increased by the third day after infarction but subsequently decreased to the control levels. Since white cells can cause blockage of narrow blood vessels, it is assumed that such changes in cellular properties may influence the eventual extent of infarction.

Aged↗
PubMed1988

White cell accumulation in dependent legs of patients with venous hypertension: a possible mechanism for trophic changes in the skin.

The mechanism by which chronic venous insufficiency and venous hypertension are associated with ulceration of the legs is not yet understood. To investigate this mechanism further accumulation of white cells in the dependent legs of normal volunteers, patients awaiting surgery for simple varicose veins, and patients with chronic venous insufficiency was studied. About 24% fewer white cells than in normal subjects left the dependent foot of patients with venous hypertension, and this trapping of white cells, was reversed when the foot was raised; similar changes were not observed in normal subjects or patients with varicose veins. The trophic skin changes typically seen in patients with venous hypertension may be aggravated by damage caused by the repeated accumulation of white cells in the microcirculation.

Adult↗
PubMed1988

Abnormal flow properties of white blood cells in patients with severe ischaemia of the leg.

The possible role of white blood cells in tissue ischaemia has attracted recent interest. White blood cells can block narrow vessels, particularly if perfusion pressure is reduced or if the cells become activated. To investigate the role of white blood cells in ischaemia microfiltration techniques were used to measure the flow properties of these cells in patients with severe leg ischaemia before and after amputation. Compared with controls white blood cells from patients showed impaired ability to flow through 8 micron and 5 micron pore filters. This applied to fractionated granulocytes and mononuclear cells as well as to unfractionated mixed white blood cells. White blood cells from blood draining the ischaemic leg had worse filterability than those from arm blood of the same patients. After amputation of the ischaemic leg there was definite improvement, the flow properties of the cells being no longer significantly different from controls. These abnormalities detected in white blood cells probably reflect activation of the cells by factors released in the ischaemic tissue. As activation alters the mechanical and adhesive properties of white blood cells, a vicious cycle of microcirculatory trapping at low perfusion pressure, activation, tissue damage, and further activation and trapping might contribute to the progressive worsening of tissue ischaemia.

Aged↗
PubMed1988

Causes of venous ulceration: a new hypothesis.

Previous hypotheses about the causes of venous ulceration are inconsistent with recently published data. In patients with chronic venous insufficiency the number of functioning capillary loops visible in the skin on microscopy fell after the legs had been dependent for 30 minutes. Another study had shown that leucocytes became trapped in the circulation in dependent legs. A new hypothesis linking these two findings proposes that the trapped white cells occlude the capillaries and result in ischaemia of the skin of the leg.

Chronic Disease↗
PubMed1988

The use of the selective serotonin S2 receptor antagonist Ketanserin in the treatment of Raynaud's phenomenon.

Ketanserin, a selective S2-receptor antagonist was evaluated in a double-blind parallel placebo-controlled trial of 29 patients with Raynaud's phenomenon. The effect on finger blood flow was assessed by strain-gauge plethysmography during a standardised cooling stress. Ten normal healthy controls also had finger blood flow assessments made in the same way. The Ketanserin group showed a significantly greater improvement (P less than 0.05) in finger blood flow at minimum flow temperature than the placebo group. The results suggest that the local release of serotonin may play a role in Raynaud's phenomenon and that Ketanserin can modify the abnormal response in finger blood flow.

Adult↗
PubMed1988

Methods and theory for analysis of flow of white cell subpopulations through micropore filters.

Methods have been developed for analysing the resistance of WBC to flow, by measuring their transit rates through 5 and 8 microns pore filters at constant pressure. Unfractionated WBC and separated subpopulations have been compared. For either pore size, lymphocytes exhibited least resistance to flow, followed by granulocytes, with monocytes being most resistant. A theoretical model, which represents WBC suspensions as made up of three particle types (a relatively fast and a relatively slow population, plus a pore blocking population) adequately describes the data for flow rate versus volume filtered. For 5 microns pores, this theory indicates that a majority of WBC have transit times approximately less than 0.5 s. Unfractionated and mixed mononuclear samples contained a proportion of particles with transit times an order of magnitude longer, whereas, for granulocytes, no slow flowing population was evident. Removal of monocytes by plating out, reduced the proportion of the slow particles in the mononuclear preparation. Unique values for transit times could not be determined for 8 microns pores, but it could be concluded that the great majority of WBC made a very quick transit, with the flow becoming dominated by a small number of much more resistant cells. Simple flow parameters (initial relative flow rate and slow particle resistance) are described which characterize these two populations. Both 5 and 8 microns pore data indicated that few cells became permanently trapped within pores.

Granulocytes↗
PubMed1988

Effects of preparative procedures and of cell activation on flow of white cells through micropore filters.

Using newly developed filtration techniques to analyse the flow resistance of white blood cells (WBC), the effects of preparative procedures and of various treatments (including activation) have been tested. Flow rates of WBC were measured using both 5 and 8 micron pore filters. It was found that EDTA was the anticoagulant of choice over heparin and sodium citrate, and that calcium-containing media should be avoided because they promoted cell-cell aggregation. Exposure to density separation media did not significantly alter filtration rates, but storage of prepared WBC for even 1 h caused deterioration in flow. Storage of whole blood before preparation of the WBC had a much lesser effect. Storage appeared to be linked to cell activation, and use of the activating agents phorbol ester (PE, 4.5 x 10(6) M/l) and f-methyl-leucyl-phenylalanine (FMPL, 10(-7) and 10(-9) M/l) also increased WBC resistance to pore transit. The effect of PE was greater, causing rapid pore blockage, but was non-specific, while the lesser effect of FMLP was restricted to granulocytes and was concentration dependent. Cell volume was increased by these agents, but measurement of the filterability of hypotonically swollen granulocytes showed that volume changes alone only partly explained the activation effects. These results suggest that activation in vivo would have a significant rheological effect, detectable by filtration methods.

Anticoagulants↗
PubMed1987

Leukocytes and the risk of ischemic diseases.

Predictive indexes for atherosclerotic risk are imperfect, suggesting that there are predictive factors not commonly considered. Such a factor may be the white blood cell (WBC) count. Epidemiologic studies have shown correlations between the WBC count and the risk of myocardial infarction and stroke. The risk of acute myocardial infarction is approximately four times as great in persons with WBC counts high in the normal range (greater than 9000/microL [9 X 10(9)/L]) as in persons with WBC counts low in the normal range (less than 6000/microL [6 X 10(9)/L]); only 50% to 65% of the excess risk of the high-count individuals is explainable by tobacco smoking (which covaries with WBC count). A high WBC count also predicts greater risk of reinfarction and of in-hospital death. Less rigorously studied, the constitutional neutropenia of Yemenite Jews appears to afford protection against atherosclerotic disease. Among WBC types, the strongest epidemiologic association has been with the neutrophil count. Such a predictive value of WBC count is plausible and satisfying, because WBCs make a major contribution to the rheologic properties of blood; alter adhesive properties under stress--including the stress of ischemia, enhancing their rheologic importance; and participate in endothelial injury, both acutely and chronically, by adhering to endothelium and damaging it with toxic oxygen compounds and proteolytic enzymes. Techniques newly developed or under development may allow us to refine the predictive value of the WBC count by combining it with measures of cell activation and/or activatability.

Blood Vessels↗
PubMed1987

Effect of defibrinogenation on the early patency rate of experimental small calibre arterial grafts.

The effect of defibrinogenation with Arvin was studied in a new animal model of early thrombosis of a 3 mm diameter polytetrafluoroethylene (PTFE) graft with a poor run-off. Fifteen control animals were compared with fourteen animals treated with subcutaneous Arvin 20 units kg-1 body weight day-1, starting 2 days before surgery and continuing for 2 days postoperatively. The peroperative fibrinogen level in the controls was 2.8 +/- 0.9 gl-1 compared with 0.4 +/- 0.3 gl-1 in the treated group. There was no significant difference in the peroperative or postoperative platelet count or haematocrit value between the two groups. Plasma viscosity and whole blood viscosity (at a low shear rate of 0.7s-1) were significantly less during and after surgery in the defibrinogenated group. The degree of defibrinogenation in these animals produced no problems with haemostasis during surgery or in the postoperative period. The cumulative patency rates of the controls at 24 h, 48 h, and 4 days were 43 per cent, 28 per cent and 28 per cent compared with 86 per cent (P less than 0.05), 73 per cent (P less than 0.05) and 73 per cent (P less than 0.05) respectively in the defibrinogenated group. In this model of a narrow PTFE graft with a poor run-off, defibrinogenation was a safe and effective method of improving early patency of small calibre arterial grafts.

Ancrod↗
PubMed1987

Serotonin and haemorrheology.

One of the crucial determinants of tissue perfusion is the flow behaviour, that is the rheology, of the blood itself. In the microcirculation the most important factor is the ability of the cellular components of blood to deform as they pass through the narrower capillary passages. Until recently, it was thought that the deformability of the red cells was more important than that of the white cells, because of their numerical superiority. Recently, the flow behaviour of white cells is thought to be at least equally important. There is now extensive epidemiological, experimental and clinical evidence linking the microrheological properties of blood to tissue ischaemia. The possible role of serotonin in altering haemorrheology is inferred from studies using specific serotonin antagonists. Ketanserin, given orally has been shown to improve blood filterability in patients with myocardial infarction and intermittent claudication. There was also a specific effect on white cells. It is postulated on the basis of these and other experiments that in situations of tissue ischaemia, when there is a local increase in plasma serotonin levels, the deleterious effect of serotonin on blood cell rheology may have an important role in perpetuating the ischaemia.

Blood Viscosity↗
PubMed1986

Transcutaneous oxygen tension during exercise in patients with claudication.

Transcutaneous oxygen tension (TcPO2) was monitored during maximal exercise in 10 patients with stable moderate to severe claudication. The TcPO2 fell by 16% at the onset of claudication and 32% at the maximum walking distance. On resting this decrease reached a maximum of 66% roughly four minutes after exercise. This was followed by a steady recovery. The percentage changes were reproducible in each patient and were appreciably different from the TcPO2 exercise profiles of normal healthy volunteers. TcPO2 monitoring during exercise is a simple, reproducible, cheap, and useful technique for assessing claudication and compares favourably with other techniques used to quantify this condition.

Aged↗
PubMed1986

The effect of normovolaemic haemodilution on the early patency rate of small calibre vascular prostheses studied in a new animal model.

A new animal model has been developed to study early thrombosis in small calibre vascular prostheses. It consists of an ePTFE graft 2 cm long and of 3mm internal diameter inserted into a rabbit abdominal aorta in which the distal run-off is reduced by narrowing both common iliac arteries using clips with a standard gap. Scanning electron microscopy and in vivo gamma imaging of the graft using labelled autologous platelets showed that, as in the human, platelets played a primary role in the model graft thrombosis. This model was used to study the effect of haemodilution on early graft patency. Moderate normovolaemic haemodilution dramatically improved the early patency rate.

Animals↗
PubMed1986

The clinical relevance of the flow properties of blood cells.

In the recent years hemorheology has gained increasing interest in medicine and contributed to new understanding of the role of blood fluidity with regard to microcirculation especially in chronic occlusive vascular disease. Various hemorheologic factors have been uncovered as being of significance in physiologic and pathologic flow conditions. Primarily the deformability of red cells was in the center of interest and various devices mostly based on filtration systems, were introduced for the measuring of red cell's ability to deform. In the last few years the role of white cells came into play especially in conditions of low perfusion pressure in ischaemic areas. Since it is plausible that in capillaries white cells can hold up a very much larger number of red cells it is most likely that the rheological properties of white cells play a governing role in areas of ischaemia and infarction in respect of blood fluidity, flow and prognostic aspects. A new filtration device is now available which can distinguish between the resistance to flow of the rheologically predominant cell type of a suspension (initial filtration rate) and the number of rigid cells blocking the filter pores (clogging rate). Intensive studies will be necessary to clarify the rheological behaviour of the different types of white cells.

Blood Viscosity↗