Acute Impact of Different Exercise Modalities on Arterial and Platelet Function.

PURPOSE: Acute coronary syndromes and ischemic stroke are associated with arterial events involving platelets, the endothelium and atherosclerosis. Whilst regular physical activity is associated with lower risk of cardiovascular events and mortality, risk is transiently increased during and immediately following participation in an acute bout of exercise. No previous study has investigated the acute impact of exercise on platelet activation and arterial function in the same participants; it is also unknown if responses are dependent on exercise modality. We hypothesised that commonly adopted, yet physiologically distinct, modalities of exercise ("aerobic" versus "resistance") have differing effects on in vivo platelet activation and conduit artery diameter. METHODS: Eight apparently healthy middle-aged (53.5±1.6yrs) male subjects took part in four, 30 min experimental interventions (aerobic AE, resistance RE, combined aerobic/resistance exercise CARE or no-exercise), in random order. Blood samples were collected and the measurement of brachial artery diameter by ultrasound was performed before, immediately after, and one hour after each intervention. Platelet activation was determined by the positive binding of antibodies to surface receptors exposed on activated platelets (anti-CD62P and PAC-1). RESULTS: Brachial artery diameter increased immediately following all three exercise modalities (P<0.001), and remained above pre-exercise levels 1hr post-RE and -CARE. No changes were observed in markers of in vivo platelet activation with any experimental protocol. CONCLUSION: These data suggest that post-exercise enhancement in arterial function may mitigate the acute impact of exercise on platelet activation

Computational Lipidology: Predicting Lipoprotein Density Profiles in Human Blood Plasma

Monitoring cholesterol levels is strongly recommended to identify patients at risk for myocardial infarction. However, clinical markers beyond “bad” and “good” cholesterol are needed to precisely predict individual lipid disorders. Our work contributes to this aim by bringing together experiment and theory. We developed a novel computer-based model of the human plasma lipoprotein metabolism in order to simulate the blood lipid levels in high resolution. Instead of focusing on a few conventionally used predefined lipoprotein density classes (LDL, HDL), we consider the entire protein and lipid composition spectrum of individual lipoprotein complexes. Subsequently, their distribution over density (which equals the lipoprotein profile) is calculated. As our main results, we (i) successfully reproduced clinically measured lipoprotein profiles of healthy subjects; (ii) assigned lipoproteins to narrow density classes, named high-resolution density sub-fractions (hrDS), revealing heterogeneous lipoprotein distributions within the major lipoprotein classes; and (iii) present model-based predictions of changes in the lipoprotein distribution elicited by disorders in underlying molecular processes. In its present state, the model offers a platform for many future applications aimed at understanding the reasons for inter-individual variability, identifying new sub-fractions of potential clinical relevance and a patient-oriented diagnosis of the potential molecular causes for individual dyslipidemia

Glucose and lactate turnover in adults with falciparum malaria: effect of complications and antimalarial therapy

Hypoglycaemia and lactic acidosis are potentially life-threatening, poorly understood sequelae of Plasmodium falciparum infections. We investigated relationships between clinical status, treatment, and glucose and lactate kinetics during management of falciparum malaria in 14 Vietnamese adults. Nine had severe malaria, of whom 4 were administered quinine (Group la) and 5 artesunate (Group 1b). Five uncomplicated cases received artesunate (Group 2). Glucose and lactate turnover were studied on 3 occasions: (i) immediately after initial antimalarial treatment, (ii) at parasite clearance a median of 3 days later, and (iii) at discharge from hospital a median of 9 days post-admission. Steady-state glucose and lactate kinetics were derived from plasma isotopic enrichment during a primed-continuous infusion of D-[6,6-D-2] glucose and a parallel infusion of L-[1-C-13]lactate. Group la patients had the lowest plasma glucose concentrations in the admission study (median [range] 3(.)9 [3(.)6-5(.)1] vs 6(.)3 [4-9(.)7-1] and 4(.)5 [4(.)3-5(.)5] mmol/L in Groups 1b and 2 respectively; P 0.17). This was also the case at parasite clearance and suggested an inappropriate beta cell response. Group la patients had the highest admission lactate production (60 [36-77] vs 26 [21-47] and 22 [4-31] mumol/kg.min in Groups lb and 2 respectively; P < 0.05 vs Group 2). Amongst the 9 severe cases, there was an inverse association between plasma glucose and lactate production at admission and parasite clearance (P < 0.05), but no correlation between admission lactate production and serum bicarbonate (P = 0(.)73). The present data confirm previous studies showing that quinine depresses plasma glucose through stimulation of insulin secretion. It is hypothesized that the low plasma glucose activates Na+,K+-ATPase through increased plasma catecholamine concentrations, leading to accelerated glycolysis and increased lactate production in well-oxygenated tissues. In some severely ill patients with falciparum malaria, a raised plasma lactate on its own may, therefore, be an unreliable index of a developing acidosis