Study of skin microvascular function in Raynaud’s phenomenon : a pathophysiological and pharmacological approach

Abstract : The cutaneous microcirculation has been proposed as a model to study generalized microvascular function in various diseases. Moreover, it is specifically affected in Raynaud’s phenomenon, characterized by transient ischemia in the digits in response to cold. Despite recent advances in methods exploring the cutaneous microcirculation, they still suffer from a lack of standardization. In the first part of this dissertation, we have reviewed the different techniques used to assess skin microvascular reactivity, and studied the reproducibility of reactivity tests. We then used these tests to assess cutaneous microvascular reactivity in Raynaud’s phenomenon, and showed abnormal neurovascular control of the microvasculature in these patients. The third part of this dissertation is dedicated to pharmacological studies targeting the cutaneous microcirculation in Raynaud’s phenomenon. We tested the effect of sildenafil, a phosphodiesterase-5 inhibitor, on digital skin blood flow while cooling locally, and showed increase in cutaneous vascular conductance in patients with Raynaud’s phenomenon. Finally, we assessed in animals and in humans the effect of locally administered vasodilating drugs on the cutaneous microcirculation, by using iontophoresis. This innovative approach may be an interesting treatment in Raynaud’s phenomenon.


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Submitted on : Wednesday, October 19, 2011 - 3:57:46 PM
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Matthieu Roustit. Study of skin microvascular function in Raynaud’s phenomenon : a pathophysiological and pharmacological approach. Pharmacology. Université de Grenoble, 2011. English. <NNT : 2011GRENS023>. <tel-00633855>

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