Inflammatory Response in Peripheral Arterial Disease

Research output: ThesisDoctoral Thesis (compilation)

Abstract

Peripheral arterial disease (PAD) is the manifestation of atherosclerotic lesions in arteries supplying blood to the legs. Atherosclerosis is now recognized as an inflammatory disease of the vessel wall and important features in the pathophysiology are activation of WBC, endothelial cells and increased levels of inflammatory mediators. The inflammatory response in PAD is further influenced in case of infected ulcers, or related to interventional procedures to restore the blood flow. Possibly, the ischemia per se may initiate a low grade of inflammatory activity that could be of clinical relevance. Diabetes mellitus is associated with an aggressive form of atherosclerosis with an early manifestation in the leg arteries. The metabolic stress is a key feature in the pathophysiology that probably increases the inflammatory activity in the vessel wall. An adequate local metabolism is important for tissue survival. Prostacyclin produced by the endothelial cells protects the circulation and treatment with synthetic prostacyklines is the only established drug therapy that in a proportion of patients has clinical effects in leg ischemia. The aim of this thesis has been to describe the inflammatory response in PAD and the effects of endovascular and open surgical procedures. Besides, effects on the local metabolism in critical leg ischemia of a prostacyclin analogue treatment were studied by a microdialysis technique.

In patient groups with PAD, activation of white blood cells was significantly increased compared to a control group. The increased inflammatory response was mainly correlated to severe leg ischemia but not to the presence of ulcers, gangrene or diabetes mellitus. Neither was polymorphism in the IL-6 gene correlated to PAD. Following balloon angioplasty the response was limited but a significant downregulation of WBC detected in the systemic circulation was observed after the procedure which could indicate an accumulation of activated cells to the injured endothelium. Revascularisation in severe leg ischemia with rest pain only, did not influence the inflammatory response, suggesting that ischemia per se is not a source of inflammation. In severe leg ischemia, treatment with a prostacyclin analogue did not influence glucose or lactate levels during treatment days, but a significant difference to a preceding control day might indicate an effect on the local metabolism.

Details

Authors
  • Peter Danielsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Clinical Medicine

Keywords

  • muskelsystem, reumatologi, rheumatology locomotion, Skelett, Skeleton, Polymorphism, Metabolism, Prostacyclin, Microdislysis, Diabetes mellitus, Revascularisation, Angioplasty, Endothelial cells, White blood cells, Inflammation, Peripheral Arterial Disease, muscle system
Original languageEnglish
QualificationDoctor
Awarding Institution
Supervisors/Assistant supervisor
  • [unknown], [unknown], Supervisor, External person
Award date2004 Oct 22
Publisher
  • Medicinsk Informationsteknik, Malmö
Print ISBNs91-628-6191-3
Publication statusPublished - 2004
Publication categoryResearch

Bibliographic note

Defence details Date: 2004-10-22 Time: 10:15 Place: Lecture hall , ing 42 UMAS, Malmö External reviewer(s) Name: Wahlberg, Eric Title: Doc Affiliation: [unknown] --- Article: I. Danielsson P, Schatz P, Swartbol P, Truedsson L, Danielsson G, Zdanowski Z, Albrechtsson U, Norgren L. Response of inflammatory markers to balloon angioplasty in peripheral arterial occlusive disease. EJVES 2000; 20:550-5 Article: II. Danielsson P, Danielsson G, Truedsson L, Norgren L. White blood cell and endothelial cell response to endovascular procedures in the leg. Int. Angiology 2004 (in press) Article: III. Danielsson P, Truedsson L, Norgren L. Systemic white blood and endothelial cell response after revascularisation of critical limb ischemia is only influenced in case of ischemic ulcers. ( manuscript ) Article: IV. Danielsson P, Truedsson L, Norgren L. Inflammatory markers and IL-6 polymorphism in patients with peripheral arterial disease with and without diabetes mellitus. (submitted) Article: V. Danielsson P, Metzsch C, Norgren L. Effect of Iloprost infusion on metabolism in critical limb ischemia, utilizing microdialysis – A pilot study. Int. Angiology 2004 (in press) The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Internal Medicine (013242500), Emergency medicine/Medicine/Surgery (013240200)