Platelet Functions in Cardiopulmonary Bypass Surgery

Background

Haemorrhage after Cardio Pulmonary Bypass (CPB) Surgery is a well recognised complication that leads to significant morbidity and mortality. The incidence varies between 5-25% depending upon the clinical situation. Several factors are implicated as causative but none have been precisely proved.

Methods

Our study was an attempt to evaluate the haemostatic defect with particular reference to platelet function abnormalities during cardio pulmonary bypass surgery, in order to reduce the morbidity and mortality associated with post CPB haemorrhage. Flow cytometric evaluation of different platelet glycoproteins like GPIb/IX, GPIIb/IIIa and GMP-140 was done.

Results

The marker expression showed deregulation during surgery which returned to base after bypass was terminated. In contrast, the cases with bleeding showed significant variation. P-Selectin (GMP 140) expression decreased progressively till 3^rd post-operative day showing lack of activation of platelets in cases of severe bleeding.

Conclusion

Longer duration of CPB initiates plasmin generation through heparin, which raises the PAI-1-tPA complex and thereby down regulating the functions of platelets. This suggests a link between duration of CPB, bleeding, platelet dysfunction and fibrinolysis. Hence serial estimations of the levels of GMP-140 and tPA can predict severe bleeding.Key Words: CardioPulmonary Bypass, Platelet dysfunction, flowcytometry, platelet glycoproteins, haemorrhage     

Acquisition and retrieval of information in amphetamine-treated hyperactive children

State-dependent learning and memory (retrieval) processes were examined in 15 amphetamine-treated hyperactive boys. While stimulant treatment enhanced the acquisition of information and its retrieval 24 hours later, there was no evidence of poorer retrieval of information learned in a state different from the retrieval state. Amphetamine appeared particularly to facilitate effortful cognitive processes. Subgroups of hyperactive children respond to amphetamine treatment in different ways, some showing changes in motor restlessness and others changes in cognition. The lack of dissociative effects when information is learned and recalled under different drug conditions suggests that what the stimulant-treated child learns can be effectively recovered after completion of treatment.     

A Finite Volume Method for Modeling Discontinuous Electrical Activation in Cardiac Tissue

This paper describes a finite volume method for modeling electrical activation in a sample of cardiac tissue using the bidomain equations. Microstructural features to the level of cleavage planes between sheets of myocardial fibers in the tissue are explicitly represented. The key features of this implementation compared to previous modeling are that it represents physical discontinuities without the implicit removal of intracellular volume and it generates linear systems of equations that are computationally efficient to construct and solve. Results obtained using this method highlight how the understanding of discontinuous activation in cardiac tissue can form a basis for better understanding defibrillation processes and experimental recordings.     

The influence of unequal numbers of trials on comparisons of average event-related potentials

Four studies examined (a) how event-related potentials (ERPs) change as the number of trials averaged increases and (b) the statistical implications of comparing ERPs composed of different numbers of trials. Experiment 1 utilized data from 7-year-old children performing an oddball task. The other three experiments used simulated data with different distributions of P3 peak latency. In all 4 experiments, peak amplitude decreased and the mean amplitude of the 300 to 900 msec interval remained stable as the number of trials averaged increased. The standard deviations of both measures decreased. These data show that the decrease in peak amplitude with increasing numbers of trials that has been found in other studies is not solely due to the elimination of residual noise but is likely to also involve a fundamental aspect of signal averaging and the algorithm used to select peaks. Furthermore, these experiments expose the possibility of statistical errors when investigators compare average ERPs composed of small versus large numbers of trials as is often done when the oddball paradigm is used.     

Isolation of two phenylethanoid glycosides from Eremophila gilesii

The leaves of Eremophila gilesii have been used traditionally to treat colds, headaches, sores, and chest pains. Our previous screening of Australian native plants showed that the methanol extract of the aerial parts of E. gilesii demonstrated notable inhibition of ADP-induced human platelet aggregation and serotonin release. Subsequent fractionation on the methanol extract led to the isolation of two phenylethanoid glycosides, verbascoside (1) and poliumoside (2). This is the first study reporting the presence of phenylethanoid glycosides in E. gilesii.     

The first potent and selective non-imidazole human histamine H4 receptor antagonists

Following the discovery of the human histamine H4 receptor, a high throughput screen of our corporate compound collection identified compound 6 as a potential lead. Investigation of the SAR resulted in the discovery of novel compounds 10e and 10l, which are the first potent and selective histamine H4 receptor antagonists to be described.     

ERP abnormalities of illusory contour perception in Williams syndrome

Williams syndrome is a genetic disorder in which visuo-spatial performance is poor. Theorists have claimed that the deficit lies in high-level processing, leaving low-level visual processes intact. We investigated this claim by examining an aspect of low-level processing, perceptual completion, i.e. the ability of this clinical group to perceive illusory Kanizsa squares. We then used event-related potentials to examine neural correlates of perceptual completion. While participants were able to perceive illusory contours, the neural correlates of this apparently normal perception were different from controls. Such differences in low-level visual processes may significantly impact on the development of higher-level visual processes. We conclude that, contrary to earlier claims, there is atypical neural processing during low-level visual perception in Williams syndrome.     

The Insulin Hypoglycemia Test: Hypoglycemic Criteria and Reproducibility

The insulin hypoglycemia test (IHT) is widely regarded as the "gold standard" for dynamic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. This study aimed to investigate the temporal relationship between a rapid decrease in plasma glucose and the corresponding rise in plasma adenocorticotropic hormone (ACTH), and to assess the reproducibility of hormone responses to hypoglycemia in normal humans. Ten normal subjects underwent IHTs, using an insulin dose of 0.15 U/kg. Of these, eight had a second IHT (IHT2) and three went on to a third test (IHT3). Plasma ACTH and cortisol were measured at 15-min intervals and, additionally, in four IHT2s and the three IHT3s, ACTH was measured at 2.5- or 5-min intervals. Mean glucose nadirs and mean ACTH and cortisol responses were not significantly different between IHT1, IHT2 and IHT3. Combined data from all 21 tests showed the magnitude of the cortisol responses, but not the ACTH responses, correlated significantly with the depth and duration of hypoglycemia. All subjects achieved glucose concentrations of of < or = 1.6 mmol/l before any detectable rise in ACTH occurred. In the seven tests performed with frequent sampling, an ACTH rise never preceded the glucose nadir, but occurred at the nadir, or up to 15 min after. On repeat testing, peak ACTH levels varied markedly within individuals, whereas peak cortisol levels were more reproducible (mean coefficient of variation 7%). In conclusion, hypoglycemia of < or = 1.6 mmol/l was sufficient to cause stimulation of the HPA axis in all 21 IHTs conducted in normal subjects. Nonetheless, our data cannot reveal whether higher glucose nadirs would stimulate increased HPA axis activity in all subjects. Overall, the cortisol response to hypoglycemia is more reproducible than the ACTH response but, in an individual subject, the difference in peak cortisol between two IHTs may exceed 100 nmol/l.