title: Microvascular function in normal and complicated pregnancy
Creators: name: Ramsay, Jane Elizabeth
Publisher: name: University of Glasgow
Year: 2002
Subjects: subject: Physiology, Obstetrics

description: Microvascular dysfunction has been proposed as a link between clinical risk factors and cardiovascular disease. Many of these risk factors have also been proposed to predispose to complications of pregnancy such as pre-eclampsia and intrauterine growth restriction. My aims therefore, were to consider cardiovascular risk factors in relation to microvascular function in normal and complicated pregnancy using the novel, non-invasive technique, laser Doppler perfusion imaging in an attempt to examine potential mechanisms of such complications. In chapter two I describe the development of our methodology for in-vivo examination of skin microvascular function, using iontophoresis of acetylcholine (ACh), an endothelium dependent vasodilator, and sodium nitroprusside (SNP), an endothelium independent vasodilator, in conjunction with a laser Doppler perfusion imager. In chapter three I examined the possible mechanisms of this effect in an attempt to reduce or eliminate this artefact. I noted voltage across chambers containing drug and salt solutions were significantly lower than the voltage profile of H2O alone and eliminated this artefact. Voltage time integral rather than charge was the prime determinant of electrically induced hyperaemic responses. Hyperaemic responses appeared to be prostaglandin dependent as they were ablated by cyclooxygenase inhibition. Therefore, use of a low resistance vehicle combined with larger chamber sizes and lower currents can prevent such artefacts, increasing the robust nature of this methodology for clinical assessment of endothelial function. In chapter four I considered the effects of the increasingly prevalent cardiovascular risk factor, obesity, on maternal metabolic and vascular function. In chapter five, I examined pregnant women with type 1 diabetes. Our aim was to compare vascular function, metabolic and inflammatory risk factors prospectively, in the antenatal and postpartum periods. In chapter six I examined cutaneous microvascular function in pre-eclamptic women. I also considered circulating markers of endothelial damage and simultaneously measured lipid and cytokine levels. In chapter seven I aimed to test the hypothesis that insulin resistance, inflammation, and hyperlipidaemia would persist in women with a history of pre-eclampsia and secondly that within this group there would exist demonstrable endothelial dysfunction. I demonstrated that women with a past history of pre-eclampsia have increased plasma concentrations of the inflammatory markers, VCAM-1 and ICAM-1 and impaired endothelial dependent vasodilatation, 15 years or more after the index pregnancy, hi conclusion therefore, these data may suggest that the phenotype associated with pre-eclampsia is linked to novel mechanisms underlying coronary heart disease. Therefore, I have developed a robust mechanism for the in-vivo assessment of cutaneous microvascular function. This has been used to demonstrate impaired microvascular responses in pregnant women with an elevated risk of cardiovascular disease in pregnancy and in later life. I have also demonstrated impaired microvascular function in women with a past history of pre-eclampsia. These observations have been closely related to both traditional (metabolic) and novel (inflammatory) cardiovascular risk factors. However, using this technique I have demonstrated that in-vivo endothelial dysfunction in women with preeclampsia may be secondary to differences in BMI. Also women with lUGR tend to be thinner and have less of an atherogenic metabolic disruption, perhaps suggesting a systemic cardio-protective role for "leanness" in this group. Leptin concentrations are elevated in pre-eclampsia, independent of BMI, and I propose roles for leptin both as a placental response to ischaeinia and in the pathophysiology of pre-eclampsia. (Abstract shortened by ProQuest.).