Inflammation in various stages of coronary heart disease
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AbstractInflammation plays a key role in atherosclerosis and acute myocardial infarction (AMI), and circulating levels of inflammatory substances may reflect the ongoing process. Lately, transplantation of stem cells from the bone marrow has been suggested as a treatment option in AMI.
The aim of the present thesis was to examine inflammation in patients with various stages of coronary heart disease (CHD) and during various treatment modalities, including the effects of intracoronary injection of autologous bone marrow cells (mBMC) on left ventricular function in AMI.
We found reduced levels of pro-inflammatory markers in patients treated with aspirin 160 mg daily compared to warfarin for up to 4 years after an acute MI. However, these findings were not reflected in the incidence of clinical end-points after 4 years.
In patients with stable CHD 1 year treatment with aspirin 160 mg daily and clopidogrel 75 mg daily induced similar reduction in the levels of TNF and MCP-1, possibly by different mechanisms.
In patients with acute ST-segment elevation myocardial infarction treated with PCI a marked short term increase in circulating levels of IL-6 and CRP as well as of IL-10 compared to similarly treated patients with stable angina pectoris appeared. The PCI procedure per se also induced an increase in IL-6 levels in patients with stable angina pectoris. The myocardial infarction induced a systemic inflammatory reaction that overwhelmed the inflammatory response induced by the PCI procedure.
No effects on global left ventricular function after 6 months were obtained in patients with AMI treated with intracoronary injection of autologous mBMC 6 days after acute PCI. A short-term pro-inflammatory response that may be unfavourable, and a slightly reduced inflammatory response after 3 months that may be beneficial, were noted in the stem cell treated patients.
List of papers
Paper I Solheim S, Arnesen H, Eikvar L, Hurlen M, Seljeflot I. Influence of aspirin on inflammatory markers in patients after acute myocardial infarction. Am J Cardiol 2003; 92:843-845. Abstract.
Paper II Solheim S, Pettersen AA, Arnesen H, Seljeflot I. No difference in the effects of clopidogrel and aspirin on inflammatory markers in patients with coronary heart disease. Thromb Haemost 2006; 96:660-664. Abstract.
Paper III Solheim S, Grøgaard H, Hoffmann P, Arnesen H, Seljeflot I. Inflammatory responses after percutaneous coronary intervention in patients with acute myocardial infarction or stable angina pectoris. Submitted. 2007
Paper IV Lunde K, Solheim S, Aakhus S, Arnesen H, Abdelnoor M, Egeland T, Endresen K, Ilebekk A, Mangschau A, Fjeld JG, Smith HJ, Taraldsrud E, Grøgaard HK,Bjørnerheim R, Brekke M, Muller C, Hopp E, Ragnarsson A, Brinchmann JE, Forfang K. Intracoronary injection of mononuclear bone marrow cells in acute myocardial infarction. N Engl J Med 2006; 355:1199-1209. Abstract.
Paper V Solheim S, Seljeflot I, Lunde K, Aukrust P, Yndestad A, Grøgaard H K, Aakhus S, Forfang K, Arnesen H. Inflammatory responses after intracoronary injection of autologous bone marrow cells in patients with acute myocardial infarction. Am Heart J. 2008 Jan;155(1):55.e1-9. Am Heart J. 2008 Jan;155(1):55.e1-9. Abstract.