Does activated neutrophil depletion on bypass by leukocyte filtration reduce myocardial damage? A preliminary report.

An important factor in the production of myocardial damage following cardiopulmonary bypass in the creation of oxygen derived free radicals. Few sources for these radicals have been identified but experimentally activated neutrophils are known to release free radical which contribute to myocyte necrosis. The aim of this pilot study was to identify whether, by depleting patients of leukocytes and particularly neutrophils on bypass, a better degree of myocardial protection could be observed using specific identifiers of myocardial damage. Ten patients undergoing urgent coronary artery bypass for unstable angina with impaired left ventricular function were leuko-depleted using a PALL medical leukocyte filter in the extra corporeal circulation together with leukocyte depletion of all transfused blood. A similar group of matched controls had only an arterial line filter without leukodepletion. All patients were operated by one surgeon using identical techniques of intermittent cross clamping and fibrillation at moderate hypothermia. Full blood count, Glutathione, Troponin T and CPK/MB were measured before, during and at identified intervals up to 72 hour after bypass. Preliminary results show little change in the total leukocyte count but the Troponin T and CPK/MB values were lower in the filtered group than in the control group and an increased level of total Glutathione in the filter group showed that there was less oxidated stress on the myocardium. Currently this filter is an expensive addition to bypass surgery but these preliminary results suggest that activated neutrophil depletion on bypass may be of benefit to patients with unstable angina, impending myocardial necrosis and low ejection fraction.

5-Hydroxytryptamine release from platelets by different red wines: implications for migraine.

We have confirmed our earlier finding that most red wines are able to bring about 5-hydroxytryptamine (5-HT, serotonin) release from platelets in vitro. Platelets from individual subjects manifested varying degrees of releasing ability but responded to different wines with a similar rank ordering. There was a high correlation (r = 0.87) between the effect of red wine and that of reserpine in different individuals. Some types of red wine caused a consistently higher release of 5-HT than others in all subjects; one red wine in particular resulted in negligible release. When several brands of this 'low-releasing' red wine were further examined, they all showed a lower activity than all the brands of a 'high-releasing' red wine type. This variation in releasing power was not related to intensity of red colour. Partial purification of red wine was achieved by column chromatography and showed releasing activity to be associated with a low molecular weight orange fraction. Preliminary studies, using solid phase extraction methods, showed that the active components lie mainly in a subgroup of the flavonoid fraction. If any of the adverse effects of red wine, such as headache induction, derive from this 5-HT releasing ability, then it may be possible to prepare red wines free from the chemical substances responsible.

Histamine, histamine H2-receptor antagonists, gastric acid secretion and ulcers: an overview.

Histamine, a biogenic amine, is involved in allergic reactions and asthma. The involvement of histamine in peptide ulcers is reviewed here. The discovery, distribution, synthesis, catabolism, and pharmacological effects of histamine are briefly described. Histamine actions are mediated by more than one type of receptor. The discovery, development and mode of action of H2-antagonists is discussed. A brief comparison of the clinical profiles (dosage regimen, metabolism and drug interactions) of the four currently used H2-antagonists (cimetidine, ranitidine, nizatidine and famotidine) is given. Furthermore, due to their ability to bind to cytochrome P-450, these compounds have the potential to interfere with the hepatic clearance of other drugs which are also metabolised by the mixed-function oxidase system in man. Therefore, a brief discussion of their adverse effects and drug interactions is included. Modulation of gastric acid secretion, in particular the role of cAMP and the proton pump, is described. Peptic ulcer is a major disease in the Western world and the aetiology and treatment of peptic ulcer are summarised.