Michael W. Rampling

Effects of components of meals (carbohydrate, fat, protein) in causing postprandial exertional angina pectoris

We have shown that unlike fat, protein, xylose, or water, the carbohydrate component of the meal accelerates myocardial ischemia, reduces exercise capacity, and is associated with a more rapid increase in the determinants of myocardial oxygen consumption than exercise in the fasting state. Our results suggest a role for a larger increase in sympathetic nervous activity and/or release of vasoactive gastrointestinal peptides after carbohydrate, but not fat or protein, meals in postprandial angina.

Pregnancy at high altitude: a hyperviscosity state

Background.  Pregnancy at high altitude has been associated with intrauterine growth restriction and preeclampsia. These conditions, at sea level, have been linked to increased hematocrit and blood viscosity. The aim of this study was to investigate the effect of high altitude on maternal hemorheology.

Factor XIII cross-linking and the rate of fibrinolysis induced by streptokinase and urokinase

Abstract The rate of lysis induced by streptokinase or urokinase of fibrin clots with varying degrees of Factor XIII cross-linking was investigated. Various techniques were used in which the plasminogen activator was uniformly distributed through the clot, or was present only at the surface. The clots were produced from purified fibrinogen solutions or from plasma. None of these ivestigations gave any evidence to indicate that lytic rates were decreased by the cross-linking of either the α or γ chains of fibrin.

Haemorheology in Gaucher disease

Abstract:  In Gaucher disease, a deficiency of glucocerebrosidase results in the accumulation of glucocerebroside within the lysosomes of the monocyte–macrophage system. Prior to the availability of enzyme replacement therapy (ERT), splenectomy was often indicated for hypersplenism. Haemorheological abnormalities could be expected in view of the anaemia and abnormal lipid metabolism in these patients and the role of the spleen in controlling erythrocyte quality. Objectives: To investigate the effect of Gaucher disease on blood and plasma viscosity, erythrocyte aggregation and erythrocyte deformability, and to determine whether observed rheological differences could be attributed to splenectomy. Methods: Haematological and haemorheological measurements were made on blood collected from 26 spleen‐intact patients with Gaucher disease, 16 splenectomised patients with Gaucher disease, 6 otherwise healthy asplenic non‐Gaucher disease subjects and 15 healthy controls. Results: No haemorheological differences could be demonstrated between spleen‐intact patients with Gaucher disease and the control group. Compared to controls, both asplenic Gaucher disease and asplenic non‐Gaucher disease study groups had a reduced MCHC (P = 0.003 and 0.005, respectively) and increased whole blood viscosity at 45% haematocrit (Hct), relative viscosity and red cell aggregation index – all measured at low shear (P < 0.05 for all). Additionally, asplenic patients with Gaucher disease alone showed an increased MCV (P = 0.006), an increased whole blood viscosity at 45% Hct measured at high shear (P = 0.019), and a reduced relative filtration rate (P = 0.0001), compared to controls. Conclusion: These observations demonstrate a direct and measurable haemorheological abnormality in Gaucher disease only revealed when there is no functioning spleen to control erythrocyte quality.

Interactions between dextran, fibrinogen and plasma membranes

Abstract FITC-labelled dextran has been used to show that there is no complex formation between fibrinogen and dextran and that the ability of dextran to reduce the flexibility of the erythrocyte does not require fibrinogen as an intermediary. Dextran was found to form a loose adherent coat on erythrocyte membranes. It was also found to adhere much more strongly to platelet membranes. It is suggested that this may affect platelet function and be a cause of the haemostatic disturbances sometimes observed after dextran infusion.

Haemorheological adaptation during pregnancy in a Latin American population

Abstract: Objective: To investigate haemorheological changes during pregnancy in a Latin American population and compare to previously published data from Caucasian populations. Design: Cross‐sectional study. Population: 75 pregnant women at 10–36 wk of gestation and 17 non‐pregnant female controls in Lima, Peru. All the women and their ancestors for three generations were born and lived at sea level. Methods: Viscosity, haematocrit and plasma fibrinogen, albumin and total protein concentrations were determined in blood samples obtained after an overnight period of fasting. Results: At 10 wk of gestation, total protein concentration and plasma viscosity were above non‐pregnant levels by about 15% and subsequently decreased linearly with gestation. Fibrinogen concentration was increased in the first trimester; it then decreased to a nadir at about 20 wk and subsequently increased. Albumin concentration decreased linearly with gestation. Haematocrit decreased from pre‐pregnancy levels at 10 wk to a nadir at about 26 wk. Blood viscosity increased in the first trimester and then decreased with gestation to a nadir at about 26 wk. Conclusion: In the first trimester of pregnancy blood and plasma viscosity are increased and they subsequently fall with advancing gestation. Plasma viscosity reflects the changes in total protein concentration, and blood viscosity is dependent on the interplay of changes in plasma viscosity and haematocrit.

A comparison of the sulphite and thrombin methods for measuring fibrinogen concentration of plasma from patients undergoing thrombolytic therapy

A thrombin method for the determination of fibrinogen concentration has been compared with a non-enzymatic sulphite precipitation method on plasma from patients undergoing thrombolytic therapy with an intermittent plasminogen/streptokinase regime. There was very good agreement between the methods even when the determinations were made in the presence of high levels of fibrinogen degradation products (FDP), provided that the thrombin clottable fibrinogen was greater than 1 mg/ml. However, after extensive fibrinogen depletion, when the thrombin method underestimates fibrinogen concentration due to significant clot inhibition by FDP, an overestimate due to co-precipitation of fragments X and Y will be obtained by the sulphite method. This suggests that the simultaneous application of both techniques may provide a simple method of assessing the presence of high levels of anticoagulant FDP in various clinical disorders.

Effect of dextran on clotting time: Steric exclusion acclerates fibrin monomer polymerisation

Abstract The thrombin clotting time of fibrinogen solutions and plasma, and the polymerisation of fibrin monomer solutions in the presence of dextran fractions of various molecular weights have been examined. Dextran shortens clotting times and increases fibrin polymerisation rates and these effects increase as the molecular weight of the dextran increases. A physico-chemical theory of polymers provides an explanation of these phenomena.