Marcomichelakis, Jiannis M.; (1996) Plasma catecholamine concentrations in response to exercise in patients with syndrome x. Doctoral thesis (Ph.D.), University College London.

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Abstract

Syndrome X is characterised by chest pain on exertion, indistinguishable from that due to myocardial ischaemia, a positive exercise test and unobstructed epicardial coronary arteries on angiography. The underlying mechanism(s) remain unresolved. A body of evidence favours the concept that in many patients myocardial ischaemia occurs due to impaired coronary artery dilator response, caused by prearteriolar vasoconstriction and sympathetic hyperactivity. The main focus of the study was to examine the effect of exercise on the catecholamines, adrenaline and noradrenaline, in patients with syndrome X, compared to a normal control group. In addition, measurements were included for blood lactate, plasma potassium, plasma bicarbonate and creatine kinase. The study population consisted of two groups, thirty patients with chest pain, a positive ECG response to exercise, a normal coronary arteriogram and a normal ventricular angiogram (syndrome X group) and thirty apparently normal non-hospital staff subjects (control group). All subjects underwent formal, symptom-limited treadmill exercise tests, according to the Bruce protocol. The study protocol involved two exercise tests in each group. In syndrome X patients the first exercise test confirmed the presence of a positive test and the second was used in the study. In the control subjects the first exercise test served as a familiarisation procedure and also to establish that the test was normal, and the second test was used for the purpose of the study. Three venous blood samples were taken with the patient supine. The first 20 minutes prior to exercising, the second immediately post-exercise and the third 20 minutes into the recovery period. Samples were analysed for adrenaline and noradrenaline blind at another hospital and for the biochemical markers by the routine hospital laboratory. Resting heart rates were similar in both the control and syndrome X groups. There was no statistical difference between them. (Two-sample t test, P=0.26). Resting blood pressures were also similar in both groups and there was no significant statistical difference between them. (Two-sample t test, systolic P=0.99, diastolic P=0.77). The duration of exercise tests was comparable in both control and syndrome X subjects and there was no significant statistical difference between them. (Two-sample t test, P=0.2). The heart rate achieved immediately after exercise was also comparable in both groups and there was no significant statistical difference between them. (Two-sample t test, P=0.5). The blood pressures achieved immediately post-exercise were again similar in both control and syndrome X groups. There was no significant statistical difference between them. (Two-sample T test, systolic P=0.56, diastolic P=0.84). The main positive finding of this study was that the increase in plasma noradrenaline concentration from pre-exercise to immediately post-exercise was greater in the syndrome X group than the control group. Thus, at the 95% significance level the data is compatible with there being a difference between control and syndrome X in immediately post-exercise plasma noradrenaline concentrations. (Mann-Whitney, P=0.04). Furthermore, there was a statistical difference at the 99% level in delta plasma noradrenaline values (Mann-Whitney, P=0.005) and percentage noradrenaline increases from pre-exercise to immediately post-exercise (Mann-Whitney, P=0.002) between the two groups. Resting, pre-exercise supine plasma catecholamine levels were similar in both control and syndrome X groups. (Mann-Whitney, adrenaline P=0.82, noradrenaline P=0.12). Resting, pre-exercise supine other metabolic levels were also similar in both groups. (Lactate P=0.24, potassium P=0.16, bicarbonate P=0.56, creatine kinase P=0.96). No significant differences were observed between the control and syndrome X groups in values from pre-exercise to immediately post-exercise (delta values) in respect of lactate (Mann-Whitney, P=0.61), potassium (Mann-Whitney, P=0.08), bicarbonate (Mann-Whitney, P=0.63) and creatine kinase (Mann-Whitney P=0.58) concentrations. There was no significant difference in plasma adrenaline increases from pre-exercise to immediately post-exercise (delta values) between the two groups. (Mann-Whitney, P= 0.87) There was also no relation in the syndrome X patients between delta plasma catecholamine concentration changes from pre-exercise to immediately post-exercise (delta values) and immediately post-exercise ST segment depression. (Spearman Rank Correlation Coefficient, adrenaline P[greater-than]0.2, noradrenaline, P[greater-than]0.1). These data show that the catecholamine response to exercise is different in syndrome X, in that patients with this condition increase plasma noradrenaline concentrations to a greater extent compared to apparently normal people without this condition. The data are also consistent with the view that there may be an association between sympathetic overactivity and some patients with this condition and that catecholamines, and possibly other neurotransmitters, might be implicated in the pathogenesis. A hypothesis is therefore advanced, that an enhanced catecholamine response over a period of time may have a deleterious effect on coronary artery endothelium, altering endothelial function and resulting in a susceptibility to true myocardial ischaemia during exercise.

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