Activated Protein C (APC) is an endogenous anticoagulant that regulates thrombin generation. Its physiological importance is reflected by the thrombotic phenotype of PC deficient individuals and those with APC resistance due to mutation at the Factor V cleavage site. At a molecular level, thrombin binding to the receptor thrombomodulin (TM) converts endothelial protein C receptor (EPCR) bound PC into APC. APC has a negative feedback role in curbing thrombin generation by inactivating coagulation factors V and VIII. Clinically, acquired PC deficiency occurs in conditions such as severe sepsis as a result of mechanisms involving consumption, increased degradation by proteolytic enzymes and reduced hepatic synthesis. The initial success of APC in sepsis (PROWESS Trial) over other anticoagulants is thought to relate to anti-inflammatory and cyto-protective properties The interaction of EPCR-APC with protease activated receptor-1(PAR-1}, the prototypical thrombin receptor appears to be relevant in vivo. Intravenous injection of APC into mice leads to PAR-1-dependent gene induction and interestingly gene expression profiling of cytokine-stimulated endothelial cells demonstrates marked differences between APC and thrombin signaling. Cardiovascular dysfunction occurs frequently in patients with sepsis, increasing the mortality rate significantly from 20% to 70-90%. Key observations from the PROWESS Trial highlighted a possible link between APC and cardiovascular recovery. For those with cardiovascular dysfunction at baseline, APC treatment led to a significantly greater likelihood of organ resolution. Furthermore, in the most critically ill patients with multiple organ dysfunction, time to resolution of cardiac dysfunction was significantly shorter for APC treated patients with improvements linked to overall mortality reduction. The precise cause of cardiac dysfunction in sepsis remains unclear. Endothelial activation has been implicated as has decreased contractility and impaired myocardial compliance. Postulated mechanisms include cardiac myofibrillar dysfunction with altered calcium sensitivity and the influence of myocardial depressant factors such as pro-inflammatory cytokines and nitric oxide. The potential effects of APC on the cardiovascular system could be multifactorial. This thesis sets out to examine if the anti-inflammatory and cytoprotective properties of APC may be involved. In the first experimental chapter, the effect of APC in free or microparticulate form on human coronary artery endothelial cells was examined. An anti-inflammatory and cytoprotective profile is induced although evidence of reversing the pro-inflammatory effect of tumour necrosis factor alpha (TNFo) was inconclusive. In the second experimental chapter the effect of APC on cardiomyocyte contraction was studied using rat ventricular cardiomyocytes and this showed the potential role of EPCR and PAR-1. In view of the high efficiency of PAR-1 activation by thrombin, the third experimental chapter looked at whether any APC effect would continue to be relevant in the presence of thrombin. The APC response was observed at clinically relevant concentrations, without significant modification of calcium handling and despite the presence of thrombin. This led to the final experimental chapter where PAR-1 mediated effects appear to be regulated by downstream protein kinase C alpha (PKCa) providing mechanistic insight in to the findings This thesis concludes that APC has functional relevance with respect to cardiac cells both at the endothelial and contractile level. The results offer a framework to delineate distinct pathways for improved therapeutic manipulation in the treatment of myocardial sepsis and depression.

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No description available.

Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Motivation: C-reactive protein (hs-CRP) and other risk factors such as cortisol and obesity in the diagnosis of cardiovascular dysfunction (CVD) in African and Caucasian women has become increasingly imperative when one considers the escalation of hypertension among these groups. Recent studies have explored some aspects of these risk factors and the roles that they play within hypertension and possible future risk for cardiovascular disease. Hs-CRP has been associated with the increased prevalence of hypertension and obesity. Cortisol per se has also been linked with the development of both hypertension and the hypothalamic-pituitary adrenal cortex (HPA) response. Nevertheless, the exact mechanism remains rather uncertain due to conflicting outcomes of research within different ethnic groups. Several recent investigations have, however, linked hypocortisolism with both urbanisation and a subsequent increased likelihood of hypertension within African women as they have presented increased vascular blood pressure responses. Conversely, Caucasian women have displayed an increased central cardiac reactivity. The lack of data regarding the relationship between the above-mentioned parameters within both African and Caucasian women serves as the motivation for conducting this study. Objective: To investigate hs-CRP, cortisol and hypertension as contributors to the increased likelihood of cardiovascular dysfunction in both African and Caucasian women within South Africa. hs-CRP use this through whole document please Methodology: The manuscript presented in Chapter 2 has been compiled using data obtained from the POWIRS (Profiles of Obese Women with Insulin Resistance Syndrome) study. Apparently healthy African (N=102) and Caucasian (N=115) women, matched for age and body mass index, were recruited from the North-West Province of South Africa for participation within this study. Subjects were divided into normotensive (NT) and hypertensive (HT) groups according to the mean resting cardiovascular values that were taken using a Finometer device. High-sensitivity C-reactive protein (hs-CRP) and cortisol blood serum values were determined by immunochemistry and ELISA analyses. Significant differences within each ethnic group and between each of the groups (NT and HT) were determined by analysis of covariance (ANCOVA), for anthropometric, cardiovascular, hs-CRP and cortisol variables, while adjusting for cardiovascular covariates (age, smoking and alcohol consumption). Partial correlations analyses were used to examine the relationship between hs-CRP, cortisol, anthropometric and cardiovascular parameters adjusting for cardiovascular covariates. Logistic regression analyses was used within each ethnic group to determine the relationship between anthropometric, cardiovascular, hs-CRP and cortisol as independent variables and hypertension as dependent variable. This study was approved by the Ethics Committee of the North-West University and all subjects gave informed consent in writing. For a more detailed description of the subjects, study design and analytical procedures please refer to the Materials and Methods section within Chapter 2 of this dissertation. Results and Conclusion: Both ethnic groups presented higher hs-CRP and lower cortisol levels compared to normal values. Lower waist circumference (WC) and cortisol as well as higher blood pressure (BP) and vascular values were evident in Africans compared to Caucasians. Both HT ethnic groups were older and more visceral obese compared to their NT counterparts. HT Caucasians indicated higher central adrenergic responses whilst HT Africans showed vascular adrenergicresponses. Only NT Africans had lower cortisol values than NT Caucasians but the Africans (NT and HT) responded with higher diastolic blood pressure responses compared to their Caucasian counterparts. Moreover, hs-CRP within African women significantly correlated with all BP and obesity variables whilst hs-CRP only associated with stroke volume (SV) and compliance (Cw) within HT Caucasian women. Cortisol in both ethnic groups was strongly associated with vascular BP responses. Only BP contributed to the higher prevalence of HT in both ethnic groups. In conclusion, these results suggest the possible diverse roles of HPA axis dysregulation associated with higher inflammatory responses. This happens in conjunction with cardiac and vascular responses within more obese Caucasian and especially African women, respectively. / MSc (Physiology), North-West University, Potchefstroom Campus, 2009

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

Motivation: The prevalence of cardiovascular dysfunction, especially hypertension, in Africans has increased dramatically over the past few decades. Despite considerable in~ depth studies, cardiovascular diseases remain the leading cause of morbidity and mortality. Further escalations are predicted, especially in developing countries such as South Africa, if measures are not taken to combat the trend. Numerous cardiovascular risk factors have been investigated within African-Americans as well as Caucasians. However, it is not known to what extent African-Americans and Africans from South Africa are comparable. Therefore, it is essential to investigate risk factors and their possible contributory role in the high susceptibility of cardiovascular dysfunction in the black South African population. Aim: To investigale potential risk factors and their possible involvement and association with the high prevalence of cardiovascular dysfunction within the black South African population. Methodology: Manuscripts presented in Chapters 2, 3 and 4 made use of the data obtained from the cross-sectional SAfrEIC (The South African study regarding the influence of Sex, age and ethnicity on insulin sensitivity and Cardiovascular function) study. The study group included 756 asymptomatic, apparently healthy African men and women as well as Caucasian men and women, recruited from the North West Province, South Africa. Anthropometric and cardiovascular measurements were taken as well as their lipid profiles, fasting insulin levels, and uric acid and adiponectin levels. Independent t-tests, analyses of variance (ANOVA) and analyses of covariance (ANCOVA) were used for comparison of variables between groups to determine significant differences. Partial correlations coefficients were used to show association between variables while adjusting for confounders. Multiple analyses of covariance (MANCOVA) were performed to compare variables between the groups, whilst adjusting for relevant confounders. Stepwise multiple and single regression analyses were also used to determine and confirm the most significant associations between variables. All subjects gave informed consent in writing and the Ethics Committee of the NorthWest University approved the study, The reader is referred to the "Materials and Methods" section of Chapters 2, 3 and 4 for a more elaborate description of the subjects, study design and analytical methods used in each paper. Results and conclusions of the individual manuscripts *Results from Chapter 2 revealed significantly lower uric acid levels for African men compared to Caucasian men, Despite these lower levels. the association between uric acid and blood pressure is more pronounced within the African men. The strong positive relationship between uric acid and blood pressure might be explained by uric acid's independent relationship with vascular resistance, Uric acid also revealed a positive association with triglycerides in both the African and Caucasian men. These results suggest that uric acid per se can act as a risk factor in the development of cardiovascular dysfunction in African men, *Results from Chapter 3 showed opposing changes in insulin secretion for African men and Caucasian men with increasing age. Whereas insulin levels increased in Caucasian men with progressive age, insulin levels in African men tended to decrease with ageing. Additionally, the insulin-blood pressure relationship within African men revealed opposite results as to what was expected. While the Caucasian men revealed a more positive association between insulin and blood pressure within the younger individuals, older individuals revealed a negative association between insulin and blood pressure, This implies that the vasoconstrictory actions of insulin seem to dominate in young individuals while the vasodilatory actions of insulin take over in older individuals, The turnaround probably acts as a counter protective mechanism against age-related cardiovascular dysfunction. On the contrary, despite decreased insulin secretion in older African men, they exhibit a more positive association between insulin and blood pressure, whereas younger subjects showed a more negative association, These results might suggest dissociation between insulin and blood pressure, Insulin per se might, therefore, not act as a risk factor, but rather the lack of insulin-mediated vasodilatory effects as observed within younger Africans. *Results from Chapter 4 contradicted the notion found in the literature that age-related increase in adiponectin levels are due to impaired renal function. Although the results from this chapter confirmed a Significant association between renal function (estimated creatinine clearance) and adiponectin levels a multiple regression model revealed insulin resistance (HOMA-IR) as the major contributor to adiponectin levels. Adiponectin levels increased with progressive ageing only in the Africans. No such change was observed for the Caucasians. This might be due to development of functional adiponectin resistance or perhaps due to a decline in pancreatic cell mass with ageing. In conclusion, the cardiovascular profile of Africans seems to be more detrimentally affected compared to Caucasians. Results from this study have elucidated on the associations and potential involvement of possible risk factors including, uric acid, insulin, C-peptide, as well as adiponectin, with regards to the high prevalence of cardiovascular dysfunction within the black South African population. / Thesis (Ph.D. (Physiology))--North-West University, Potchefstroom Campus, 2010.

No description available.

Coronavirus disease 2019 (COVID-19), an infectious respiratory disease propagated by a new virus known as Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has resulted in global healthcare crises. Emerging evidence from patients with COVID-19 suggests that endothelial cell damage plays a central role in COVID-19 pathogenesis and could be a major contributor to the severity and mortality of COVID-19. Like other infectious diseases, the pathogenesis of COVID-19 is closely associated with metabolic processes. Lactate, a potential biomarker in COVID-19, has recently been shown to mediate endothelial barrier dysfunction. In this review, we provide an overview of cardiovascular injuries and metabolic alterations caused by SARS-CoV-2 infection. We also propose that lactate plays a potential role in COVID-19-driven endothelial cell injury.

Author's name: Bc. Irena Malá School: Charles university, Prague 1st Faculty of Medicine Institut of Theory and Practice of Nursing Vídeňská 800, 140 59 Prague 4 - Krč Program: Health Care Administration Title: Early postoperative care of the patient with the left ventricular assist device HeartMate II Diploma thesis supervisor: PhDr. Hocková Jana, PhD. Number of pages: 170 Number of attachments: 41 Year: 2013 Key words: early postoperative care, hypotermia, blood transfusion, fluid resuscitation, perioperative cardiovascular dysfunction, pharmacologic support, ventricular assist device HeartMateII, monitoration, device, cardiac arrhythmias, ventilation management, postoperative anticoagulation, glycemic kontrol, renal insufficiency, nutrition, nursing, complications, physiotherapy, psychological aspects The occurrence of the heart failure is similar to an epidemic with high mortality. This fact, together with stagnate or even decreasing number of suitable donors, led to a need of replacing the heart pump activity with an artificial one. Mechanical cardiac support systems are sophisticated devices that are able to support a certain period of time or completely replace the function of the heart as a pump. The indications implantation of mechanical cardiac support is significant symptomatic heart...