Neuropeptide Y and platelet aggregation by adrenaline.

The effect of neuropeptide Y on platelet-rich citrated human plasma has been studied both before and after addition of adrenaline. The peptide has no aggregatory properties of its own, but in the concentrations tested it does slow and inhibit the aggregatory responses of platelets to adrenaline. This effect is dose-dependent. The implications of this finding are discussed.

A study of experimental endocarditis in pigs.

In a proposed study of fibrinolytic therapy in experimental streptococcal endocarditis, this disease was induced in pigs by preinoculation damage to the aortic valve; the technique of this is described. If untreated, the disease runs a protracted course, similar to that in man. Fibrinolytic activity, normally low in the pig, can be increased by stress, by urokinase, by plasmin and briefly by streptokinase if supplemented by human plasminogen. The proposed experiments were abandoned in pigs, chiefly because of technical difficulties in obtaining frequent samples of blood and maintaining infusions. In experiments on the response of ADP-induced aggregation of pig platelets to prostacyclin, they were found to be about 10 times more resistant than human platelets. It is suggested that this resistance to prostacyclin, together with their usually low state of systemic fibrinolytic activity, may explain the susceptibility of pigs to bacterial endocarditis.

Fibrinolytic therapy in bacterial endocarditis: experimental studies in dogs.

An investigation was undertaken to assess the value of adding streptokinase therapy to standard penicillin treatment of artificially induced infective endocarditis due to Streptococcus sanguis. In pigs a low-grade infection could be induced which closely simulated streptococcal endocarditis in man, but for technical reasons this model proved unsatisfactory for further experimentation. In dogs the induction of S. sanguis endocarditis produced a more severe illness with a short natural history. Dogs were divided into two groups, one treated with penicillin alone, the other with penicillin and streptokinase. A five-day course, in which twice daily injections of an acylated streptokinase-plasminogen complex were given, caused a substantial reduction in the size of vegetations and possibly a higher proportion of cures and less damage to the valves. Infarction of the brain, almost certainly due to embolism, was significantly greater in the streptokinase treated group, but the same was not true of the kidneys. The possible value of such treatment for certain kinds of bacterial endocarditis in man, especially in the right side of the heart, is discussed.

A study of embolism in mitral valve disease and atrial fibrillation.

A number of possible risk factors, clinical, radiological, biochemical, and social have been examined in one group of 34 cases of mitral valve disease and four of lone atrial fibrillation, all of whom gave a history of embolism, and also in a group of 24 cases of mitral valve disease who gave no such history. All were on long-term anticoagulant treatment. Comparison of the two groups disclosed no features that would distinguish those who ran the greater risk of embolism from the remainder other than that the men in the former group were older and of shorter stature. At comparable age, the women with a history of embolism had smaller left atria. Examination of a special group of nine patients who had had embolism despite anticoagulant treatment also disclosed no special features, other than a greater age at the time of their first embolism. Fibrinolytic activity was less and the level of beta thromboglobulin was greater than normal in both groups. Those with proven risk of embolism were not distinguished by higher values of this platelet protein. Neither variable correlated with the type of heart disease. No positive association was found between cigarette smoking and the risk of embolism. Embolism was significantly more likely to occur between 0801 and 1600 hours than at other times of day.

Beta-thromboglobulin in antecubital vein blood in relation to history of a stroke.

The levels of beta-thromboglobulin (BTG) have been measured in the blood of 22 male and 22 female elderly patients who gave a past history of stroke, and in 31 males and 88 females of comparable age who gave no such history. Comparisons were made within and between the groups. In the stroke patients the relationship between BTG and age was not significant for either sex, nor was there a difference between the sexes. In the BTG/time from stroke relationship the females showed significantly higher levels the longer the time that had elapsed since the stroke, and this could not be explained solely by the factor of ageing. For males, on the other hand, there was a non-significant fall in BTG with days from stroke. In 'normal' subjects the BTG/age relationship was significant in females but not in males. No significant differences were demonstrated between the BTG/age relationships between the stroke and control groups and this was true for both sexes. The potential value of estimations of BTG in the elderly is discussed.

Fibrinolytic therapy in subacute bacterial endocarditis: an experimental study.

The effect of adding fibrinolytic to penicillin therapy in experimentally induced streptococcal bacterial endocarditis has been studied in the rabbit. In 9 day old infected lesions, the vegetations could be substantially reduced in size after a 3 day course of intravenous streptokinase. Quantitative microbiological techniques demonstrated that the addition of streptokinase to standard intravenous penicillin treatment led to more rapid sterilisation of the vegetations. Embolism to lungs and kidneys was assessed in treated and untreated rabbits. Penicillin reduced the rate of embolism but the addition of streptokinase reversed this effect and gave values similar to those recorded in untreated animals.

beta-thromboglobulin in antecubital vein blood--the influence of age, sex and blood group.

Samples of blood for estimation of beta-thromboglobulin (B.T.G.) in normal subjects have been obtained both from blood donors at the end of their donation and from other volunteers by standard venepuncture. The former was a satisfactory method in males only. By standard venepuncture females have on average lower values than males and in the pre-menopausal age groups the difference is statistically significant. Mean values vary little up to 59 years after which they rise slowly but steadily. There is no significant difference in the mean B.T.G. values between the ABO blood groups.

Controlled trial of the effect of cycloalliin on the fibrinolytic activity of venous blood.

Cycloalliin is a natural constituent of onion, sulphur-containing but odourless. It was synthesised for this randomised double-blind study; its effect on fibribolytic activity and platelet aggregability was tested in venous blood from 18 male volunteers. It increased the former to a highly significant degree but had no effect on the latter. It was well tolerated and harmless in the single oral dosage used.

Circumstances attending 100 sudden deaths from coronary artery disease with coroner's necropsies.

The deaths of 100 men due to coronary artery disease which occurred so suddenly and unexpectedly as to merit a coroner's necropsy have been studied, with special reference to the exact circumstances of their occurrence. The most significant relationship of sudden death was with acute psychological stress. Moderate physical activity, the time of day, the day of the week, and a recent meal, especially if accompanied by alcohol, were also significantly related. Very strenuous exercise, the season of the year, the environmental temperature or recent change of it, and chronic psychological stress were not so related. Neither were the actual smoking of a cigarette nor the composition of the meal immediately preceding death. Compared with previous series of proved acute myocardial infarction the necropsies in these cases showed that the right coronary artery had been recently occluded by a thrombus more often than the left anterior descending. Stenosis or occlusion of the right coronary artery bore a significant relation to the suddenness of death. Special analysis of the 52 cases in which neither recent thrombus nor infarction were found did not disclose any circumstances attending death which differed from the remainder. Some comparisons are made with the circumstances attending the onset of symptoms in 100 men studied while recovering from an acute myocardial infarct.

Partial identification of the fibrinolytic activators in onion.

A steam-distilled and an ether extract of onion have both been found to enhance blood fibrinolysis without depressing fibrinogen content in groups of human volunteers. Chemical analysis has shown which sulphur-containing compounds were in highest concentration and common to both and thus likely to carry this property, but their very intense and prolonged flavour precludes their clinical use. One sulphur containing but nearly odourless compound has been identified as having indirect fibrinolytic potential. A species difference in respect of fibrinolysis has been found between English and Spanish onion but is of little importance.