Coronary Heart Disease (CETO) is one of the most common causes of mortality in industrialised societies, and it has been demonstrated elsewhere that shift workers have an increased risk of developing CHD compared to day-workers. One possible explanation for this increased risk is that a shift worker may show inappropriate postprandial responses to a night-time meal, when their biological clock is not adapted to the night shift. This could lead to an elevation in the circulating levels of certain hormones and metabolites, such as triacylglycerol (TAG) and insulin, which are known to be risk factors for CHD. This thesis investigated the relationships between meal times and postprandial hormone and metabolic responses in simulated and real-life shift-workers. The work is presented as three major clinical trials. In the first of these, a combination of timed bright light and darkness/sleep was used to induce a gradual 9-hour phase advance in 12 healthy subjects, who then underwent a rapid 9-hour phase delay. Three meal study days were arranged, to occur during the baseline condition, immediately after the rapid phase delay, so that the subjects effectively had "simulated jet lag", and two days later. Blood parameters measured included plasma glucose, insulin, proinsulin, C-peptide, non-esterified fatty acids (NEFA), TAG and glucose- dependent insulinotropic polypeptide (GIP). Substantial differences in plasma TAG and NEFA were observed in the postprandial responses when the subjects consumed an identical meal immediately after the rapid phase delay, compared with during the baseline conditions. Two days after the rapid phase delay, subjects showed inteimediate hormone and metabolite levels, suggesting that the biological clock had a major effect on these postprandial responses. In the second study, day and night-time postprandial responses were compared in a simulated shift work environment, and the effectiveness of a number of potentially beneficial procedures was investigated. These included alterations to the content of the meal consiraied prior to the night shift, bright light exposure during the night shift, and a daytime rest period prior to the night shift. As in the first study, significant differences were seen in a number of hormones and metabolites on the night shift. compared with during the day. The content of the previous meal, bright light exposure and a daytime rest period prior to the night shift all had significant effects on the night-time postprandial responses. The most exciting discovery made was that a single 8-hour night-time bright light exposure significantly lowered the TAG postprandial responses on the simulated night shift. As all the work conducted up until this point had utilised simulated conditions, it was important to illustrate that similar differences in postprandial responses at night-time could be demonstrated in "real-life shift workers". Thus, nine midwives were recruited from the Royal Surrey County Hospital, and studied on four occasions. This allowed comparison of postprandial responses on both day and night shifts, and also allowed further investigation of the effect of altering the content of the previous meal. Significant differences were again found in a number of blood parameters when the night-time and day-time responses to the test meal were compared, with the most striking being a delayed NEFA rise on the night shift, compared with during the day. In conclusion, this series of studies have illustrated that the human body responds differently to a meal consumed at night-time, compared with during the day, both in a simulated and a real-life environment. This results in variations in the levels of a number of known CHD risk factors, and may be linked with the elevated CHD risk reported in shift workers. Alteration to the meal prior to the night shift, exposure to bright light during the night shift, and instituting a rest period prior to the night shift, were all shown to be potentially beneficial in reducing the variation between day and night-time responses.

Dietary-derived lipoproteins, chylomicrons (CM) and CM remnants (CMR), have been implicated in the progression of cardiovascular disease. Retinyl esters are currently the most widely used method for monitoring CM metabolism. The availability, however, of a specific antisera to apo B-48, the protein uniquely associated with dietary-derived lipoproteins, has allowed more extensive investigation of CM and CMR metabolism. The effect of habitual, moderate levels of exercise (3 to 4 exercise sessions a week) on the lipaemic response to meals of varying fat content was assessed in young male subjects. Apo B-48, triacylglycerol (TAG) and retinyl ester were used as markers for CM particles. Active subjects had a lower response than an inactive group in all parameters measured over time after the meals. Lipoprotein lipase (LPL) activity levels measured at the end of the postprandial period were higher in the active group. The area under the time-response curves (AUC) for apo B-48 in the inactive group increased with increasing fat content of the meals, whereas the AUC for apo B-48 was the same after each meal in the active group. Validation of a specific ELISA for apo B-48 was carried out. Cross-reactivity of the antisera with low levels of apo B-100, the protein present on endogenous lipoproteins, was ruled out. The assay was specific and sensitive for measuring apo B-48 concentrations in the CM-enriched fractions. The use of the assay in the current format for plasma samples could not be fully assessed due to difficulties with isolating a pure, concentrated sample of apo B-100 and problems with reactivity between the secondary antibody used in the assay and plasma proteins. The assay was useful for showing postprandial patterns of changes in apo B-48 levels in plasma. The effects of meal frequency on the lipaemic response to a high fat test meal challenge were assessed in an intervention study. A nibbling diet was found to cause differences between the response of various parameters after the meal (NEFA-AUC, LPL activity, infranatant-TAG AUC and time to peak) compared with the normal meal frequency. The size and density distribution of CMR in plasma were investigated. Apo B-48 was found in the IDL and LDL fractions in both the postabsorptive and postprandial states. A comparison between the retinyl ester and apo B-48 responses in the postprandial studies showed that the time to peak retinyl ester level was delayed compared to apo B-48 and TAG. The importance of apo B-48 for studying the metabolism of CM and CMR metabolism was demonstrated.

Diabetes is one of the fastest growing diseases today, affecting over a million people in the UK. Numerous medical complications, such as heart disease, are regularly associated with diabetes. Despite advances in methods of diagnosis and treatment there is still a need for greater understanding of these diseases. This will include research directed towards the influence of specific treatments and reasons for the high incidence of diabetes and heart disease in 'at risk' populations. Changes in elemental status are associated as the cause or effect of various diseased states. Elemental imbalance in diabetics can result in impaired glucose tolerance and insulin resistance and in sufferers of heart disease elemental changes impair heart rate and elasticity of blood vessels. In the UK 10,000 patients with Ischaemic Heart Disease undergo coronary artery bypass grafting (CABG) surgery each year. Elemental analysis has been carried out on blood samples collected from a group of patients admitted to hospital for bypass surgery. Proton Induced X-ray Emission (PIXE) and Instrumental Neutron Activation Analysis (INAA) have been applied as complementary analytical tools for determining elemental concentrations. Differences have been examined between CABG patients with and without diabetes. Both experimental methods have been used to investigate elemental levels in whole blood, erythrocytes and plasma. Elemental concentration varied according to the blood constituent and reflected short and long-term influences on elemental homeostasis. Plasma was found to concentrate Na, Mg and Ca the highest using both experimental techniques. All blood samples were collected and prepared at St. George's Hospital, Tooting in the UK. An additional study was conducted to investigate the influence of the bypass operation on the patient's elemental status. Whole blood was obtained at pre (1h before operation), post (1-2 hours after operation) and recovery (24 hours after completion of the operation) stages of bypass surgery. Differences between the three phases were observed, individual variations have been plotted so rates of change can be seen and evaluated with the particular medical history. Concentrations of Na, Mg, Al, P, S, Cl, K, Ca and Fe in whole blood were determined. The two measurement techniques found different concentrations however results showed a general trend that post operative concentrations were elevated compared to pre operative values. Analysis of blood drawn during the recovery phase, 24 hours after the surgery, found that concentration were typically approaching pre operative levels. Both PIXE and INAA found concentrations of Na, Mg and Al peaked post operation and then decreased in the recovery phase, towards values measured pre surgery. Various factors may be responsible for the elemental changes occurring during surgery including, hormone production, routine administration of intra-operative fluids and contact of blood with non- endothelial surfaces. Hierarchical cluster analysis has been used to confirm differences between elemental levels in pre, post and recovery stages of bypass surgery. The dendograms produced indicate significant distinction between the three stages. The explosive impact of diabetes in the UK resident Asian population is discussed and the influence of diabetogenic agents introduced. Examination of research literature revealed that betel nut has been implicated as a causative agent in several medical conditions. Samples of Betel nut and six associated chewing materials widely used in Asian communities has been collected and prepared for analysis. Instrumental neutron activation analysis has been used to determine the concentration of Na, Mg, Al, Cl, Ca, V, Mn, Cu and Br in the samples by means of short-lived radionuclides.

Abstract The traditional methods of analysing heart rate variability based on means and variance are unable to detect subtle but potentially important changes in interbeat heart rate behaviour. This research was designed to evaluate the clinical applicability and prognostic significance of new dynamical methods of analysing heart rate behaviour derived from nonlinear mathematics. The study covered four different patient populations, their controls and one general population of elderly people. The first patient group consisted of 38 patients with coronary artery disease without previous myocardial infarction, the second of 40 coronary artery disease patients with a prior Q-wave myocardial infarction, and the third of 45 patients with a history of ventricular tachyarrhythmia. The fourth group comprised 10 patients with a previous myocardial infarction who had experienced ventricular fibrillation during electrocardiographic recordings. The fifth group comprised a random sample of 347 community-living elderly people invited for a follow-up of 10 years after electrocardiographic recordings. Heart rate variability was analysed by traditional time and frequency domain methods. The new dynamical measures derived from nonlinear dynamics were: 1) approximate entropy, which reflects the complexity of the data, 2) detrended fluctuation analysis, which describes the presence or absence of fractal correlation properties of time series data, and 3) power-law relationship analysis, which demonstrates the distribution of spectral characteristics of RR intervals, but does not reflect the magnitude of spectral power in different spectral bands. Approximate entropy was higher in postinfarction patients (1.17 ± 0.22), but lower in coronary artery disease patients without myocardial infarction (0.93 ± 0.17) than in healthy controls (1.03 ± 014, p < 0.01, p < 0.05 respectively). It did not differ between patients with and without ventricular arrhythmia. The short term fractal-like scaling exponent of the detrended fluctuation analysis was higher in coronary artery disease patients without myocardial infarction (1.34 ± 0.15, p < 0.001), but not in postinfarction patients without arrhythmia (1.06 ± 0.13) compared with healthy controls (1.09 ± 0.13). The short term exponent was markedly reduced in patients with life-threatening arrhythmia (0.85 ± 0.25 ventricular tachycardia patients, 0.68 ± 0.18 ventricular fibrillation patients, p < 0.001 for both). The long term power-law slope of the power-law scaling analysis was lower in the ventricular fibrillation group than in postinfarction controls without arrhythmia risk (-1.63 ± 0.24 vs. -1.33 ± 0.23, p < 0.01) and predicted mortality in a general elderly population with an adjusted relative risk of 1.74 (95% CI 1.42–2.13). The present observations demonstrate that dynamic analysis of heart rate behaviour gives new insight into analysis of heart rate dynamics in various cardiovascular disorders. The breakdown of the normal fractal-like organising principle of heart rate variability is associated with an increased risk of mortality and vulnerability to life-threatening arrhythmias.

Adaptace na chronickou hypoxii zvyšuje toleranci srdce k ischemicko-reperfuznímu poškození. Tato adaptace je umožněna řadou fyziologických změn na buněčné úrovni. Jednou z nich je změna v buněčném energetickém metabolismu. Tento proces může být regulován proteinem FTO (z angl. fat mass and obesity associated), demetylázou epigeneticky regulující buněčnou syntézu proteinů. Srdeční metabolismus může být také modulován adipokiny leptinem a adiponektinem. Cílem tohoto projektu bylo proto studovat roli FTO a adipokinů v chronicky hypoxickém srdci. Dospělí samci potkanů kmene Sprague Dawley byli adaptováni na dva modely kontinuální normobarické hypoxie (CNH; 12 % O2 a 10 % O2; 3 týdny). CNH (10 % O2) redukovala u těchto zvířat rozsah infarktu myokardu o 20 %. CNH (12 % O2) nebyla kardioprotektivní. Hladina proteinu FTO byla měřena v tkáni levých (LV) a pravých (RV) komor, stejně jako v játrech a koncovém mozku hypoxických i normoxických zvířat. Za normoxie je hladina FTO v RV o 50 % vyšší než v LV. Ve vysoce metabolicky aktivních tkáních jater a koncového mozku jsou pak hladiny FTO vyšší dokonce 6krát a 11krát. CNH (12 % O2) vedla k signifikantnímu nárůstu hladiny proteinu FTO v srdci. Jednalo se o 21% nárůst v LV a 27% v RV. Hladiny v játrech a koncových mozcích nebyly CNH ovlivněny. Silnější CNH (10 % O2)...

Coronary heart disease (CHD) has traditionally been regarded as a male disease and, because of this, the magnitude of the problem in women is often overlooked. Yet, cardiovascular disease (CVD) and CHD in particular, remains, next to cancer, the leading cause of morbidity and mortality in women. The longstanding emphasis on the problem of CHD in men, has resulted in a widespread tendency to minimise the incidence and severity of the disease in women. Moreover, most epidemiologic studies examining morbidity and mortality from CHD have focused largely on men, producing a significant gender gap in the research. The lack of information on CHD risk factors and prevention of heart disease in women in Britain is of particular concern, given that British women have one of the highest rates of coronary disease in the world. The Marks and Spencer Coronary Risk Factor Study (MSCRFS) is a cross-sectional and prospective study of CHD risk factors in female employees of the Marks and Spencer retail organisation. The present study is confined to an analysis of cross-sectional data from 14,077 women screened between June 1988 and July 1991. The prevalence and distribution of a variety of lipid, lipoprotein, biochemical, anthropometric and lifestyle-related CHD risk factors among women in the United Kingdom is described, together with their key interrelationships. In addition, the metabolic impact of exogenous hormones, specifically oral contraceptives and postmenopausal hormone replacement, is described. This study - the largest of its kind in the UK - provides reference ranges for a wide range of CHD risk factors in women in the UK, and gives a unique insight into the impact of a variety of lifestyle-related factors on CHD risk. There is an enormous potential for reducing the very high risk of CHD among women in the UK, which needs to be addressed. Based on these data, health strategies designed to reduce morbidity and mortality from CHD can be planned and implemented more effectively.

Abstract Right heart failure may be caused by several etiologic factors such as pulmonary embolism, post coronary bypass, chronic obstructive pulmonary disease (COPD) and right heart infarction. Traditionally, treatment has consisted of fluid loading (volume expansion) and the use of inotropic agents. In the present series of studies, an experimental model of acute right heart failure was developed using right heart infarct. Treatment with drugs chosen to specifically improve right heart performance was then evaluated. The drugs used in this series were aminophlline, adenosine, nitric oxide (NO) and losartan. Aminophylline transiently improved cardiac index and pulmonary vascular resistance, but simultaneously caused an increase in heart rate and a decrease in stroke volume. Although it may reduce right heart afterload, aminophylline did not improve overall cardiac function in this experimental model of right heart infarction. Adenosine affected an increase in cardiac index during the adenosine infusion and in stroke index, while pulmonary vascular resistance and mean pulmonary pressure were decreased. There was a marked decrease in systemic vascular resistance as a result of the drug. Heart rate remained unchanged by the infusion. Discontinuation of the drug resulted in a rapid reversal of the hemodynamic changes. The continuous infusion of adenosine therefore appears to cause an effective arterial vasodilation, with a consequent unloading of right heart afterload. NO treatment significantly reduced right heart afterload. A significant deterioration was observed in cardiac output as well as in left and right ventricle stroke work indices. The use of NO in this model of right heart infarct affected a decrease in both right heart afterload and left heart preload, with an overall deterioration in global hemodynamics. Losartan was shown to decrease central venous pressure and wedge pressure, while cardiac output, left ventricle stroke work and stroke volume all showed improvement. Compared to the control animals, pulmonary vascular resistance, systemic vascular resistance and systemic pressures were unaffected by the drug, as was heart rate. An inhibition of angiotensin II action may therefore be of benefit in the treatment of right heart failure symptoms during the first hours after right heart infarct.

Abstract Ischemic stroke is associated with cardiovascular autonomic nervous system (ANS) disturbances, including reduced heart rate (HR) variability and acute phase neurohumoral activation with elevated stress hormone levels. The impact of HR variability and neurohumoral factors such as natriuretic peptides on the long-term survival of patients with ischemic stroke has not been studied previously. This study was designed to evaluate cardiovascular autonomic regulation in ischemic stroke patients by assessing HR dynamics and various neurohumoral factors. The values of the assessed variables in predicting mortality were evaluated. HR variability assessments were performed in the acute phase of ischemic stroke and for a general elderly population. Various neurohumoral factors were also assessed in the acute phase of stroke. After follow-up, the survival of the subjects was assessed and the prognostic values of the measured factors were evaluated. Stroke patients were found to have cardiovascular autonomic and hormonal disturbances manifested as reduced traditional time and frequency domain measures of HR variability, altered long-term HR dynamics and elevated levels of natriuretic peptides in the acute phase. Altered long-term HR dynamics in the acute phase of stroke predicted long-term mortality after stroke and cerebrovascular mortality in the general elderly population. Neuroendocrine activation involving elevated natriuretic peptide values that were associated with high cortisol and catecholamine levels was observed in the acute phase of ischemic stroke. Neurohumoral disturbance was prognostically unfavourable. The most powerful predictors of poststroke mortality were altered long-term HR dynamics and elevated levels of natriuretic peptides and cortisol, which predicted mortality independently of the conventional risk factors in multivariate analysis. Prognostically unfavourable cardiovascular autonomic dysfunction with disturbances in the long-term behaviour of HR dynamics was found to be related to ischemic stroke. Neurohormonal activation with elevated natriuretic peptide and cortisol levels in the acute phase predicts long-term mortality after ischemic stroke.

M.Cur. (Intensive General Nursing) / The rehabilitation of the coronary artery bypass patient should be a continuation of the contact which exists during the hospitalisation phase, with specific reference to the pre-dismissal phase. As a member of the health team, the nurse makes the most important inputs during this phase because she is the one who is in constant contact with the patient and his family. The purpose of this study is to determine, by means of set criteria and within a nursing perspective, the contributions that are made by various support groups to the rehabilitation of persons who have undergone coronary artery bypass surgery.

>Magister Scientiae - MSc / Leonotis leonurus (L. Leonurus) has relatively abundant diterpenes and has been used as a traditional herbal medicine for treating several ailments including influenza, muscular cramps, skin related diseases, menstrual, antilipidemic, hyperglycaemia and hypertension. In this study, diterpenoid compounds such as; Dubiin, SaponifiedDubiin, Hispanol, Marrubiin and DC9 were isolated from L. Leonurus plant. The cardiovascular effects of these isolated compounds were investigated in order to determine the response of anaesthetised normotensive Wistar rats (in-vivo) to the compounds. Also, the druglikeness of the isolated diterpenoid compounds and their binding interaction with β1 adrenoceptor (PDB: 2Y04), angiotensin II receptor (Ang II) (PDB: 3R8A), Angiotensin converting enzyme (ACE) (PDB: 4XX3), and renin receptor (PDB: 2X8Z) by using molecular docking methods and Chemoinformatics analysis was performed (in-silico). Important molecular descriptors and molecular docking were used in our Chemoinformatics (in-silico) analysis to study the druglikeness and the binding affinity for of each molecule (Dubiin, SaponifiedDubiin, Hispanol, Marrubiin and DC9). The molecular descriptors and the binding energy were calculated by using the molecular operating environment software (MOE 2013). The lowest energy and highest cluster conformations of the molecules were further analysed. All the five (5) diterpenoids were predicted to have good oral bioavailability after oral administration and passed the BloodBrain Barrier (BBB) rules. Also, the compounds were predicted to have high probability of being good Druglike candidates, except for DC9, which is predicted to have lower possibilities of being Druglike candidate than the other diterpenoids. Furthermore, these compounds (Dubiin, SaponifiedDubiin, Hispanol, Marrubiin and DC9) were shown to interact with β1 adrenoceptors in-silico, an interaction that was confirmed in-vivo by increases in Blood pressure (SP, DP and MAP) and Heart rate (HR). In anaesthetized normotensive male Wistar rats (in-vivo), Dubiin (0.5 40mg/kg; IV), SaponifiedDubiin (0.5 60mg/kg; IV) Hispanol (0.5 40mg/kg; IV), DC9 (0.5 40mg/kg; IV) and Marrubiin (0.5 40mg/kg; IV) produced dose dependent increase in Systolic pressure (SP), Diastolic pressure (DP), and Mean arterial pressure (MAP) at all doses. Also, the compounds produced dose dependent increase in Heart rate (HR). From the in-vivo and in-silico studies it can be concluded that all the five (5) isolated diterpenoid compounds showed cardiovascular effects on Blood pressure (BP) and Heart rate (HR) by acting as β1 adrenoceptor agonists. Also, these diterpenoids compounds could be responsible for the cardiovascular effect observed in the methanol extracts from previous studies. These cardioactive compounds are prototype or ''lead compounds'' for designing and developing new nontoxic and effective drugs for cardiovascular disease (CVD) treatment.