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Coronary circulation

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Title Coronary circulation
Period 12 / 2003 - unknown
Status Completed
Research number OND1295908

Abstract

The research focuses on the transport function of the coronary vasculature, its intrinsic regulation and the factors that may limit this supply system in its function. Coronary artery disease is the main cause of decreased pump function and heart failure. The coronary circulation provides the nutrients and removes the waste products from the cardiac muscle. Thus, sufficient coronary perfusion, the so-called supply, is essential for heart function. Especially when the supply does not meet the demand cardiac problems arise in the form of ischaemic heart disease. The coronary circulation, including local cardiac perfusion, and the study of coronary bypass patency is studied in terms of function, both by the preclinical and clinical groups. With a coronary artery stenosis the distal bed can initially keep perfusion matched to demand in rest and exercise, by vasodilation, but at the expense of the range of autoregulation. With increasing stenosis severity and (acute) occlusion the system is at the end of its regulatory range. With increasing stenosis the periphery opens more and the flow reserve decreases. The research in a group of projects is concerned with the mutual interaction between endothelial cells, smooth muscle cells and cardiac myocytes. Along these lines it is of interest to study isolated blood vessels to obtain quantitative information about the interaction among the first two types of cells. Isolated coronary arterioles are compared with arterioles embedded in cardiac tissue to study the effect of surrounding tissue during hypoxia on arteriolar diameter. Isolated arterioles are also used to study the effects of hypoxia, endotoxemia and nitric oxide production including the feedback mechanisms involved. Use is made of the newly developed technique to measure local NO production in blood vessels under the influence of different stimuli such as shear and stretch. Studies on the isolated perfused papillary muscle make it possible to evaluate the interaction of all three cell types. This preparation is chosen because it is geometrically simple and perfusion is not necessary for function. How perfusion affects muscle force is investigated and how muscle contraction affects perfusion is experimentally determined and modeled. The papillary muscle is also used as a bioassy to study the effect of coronary effluent of the (isolated) heart on the muscle. In the human heart it is possible to investigate the role of the endothelium in cardiac function, i.e. interaction of endothelial cells and the cardiac myocytes. These human studies complement the basic ones. Pressure-flow relations of the coronary system are also studied in the isolated heart. The purpose is to get insight into the effects of cardiac contraction and cardiac volume on coronary flow, in the different layers of the heart. Using MRI it has been shown that coronary arteries can be visualized for the non-invasive detection of coronary artery stenoses. Furthermore, with this technique and with cardiac catheterization, the effects of stenoses on coronary flow and myocardial perfusion are investigated in humans. Intracoronary ultrasound is used to provide a better definition of coronary luminal areas, coronary plaques and flow, and has been used in combination with interventional treatment strategies. It has been shown that thrombolytic therapy in the acute stage of infarction decreases infarct size, mortality and occurrence of heart failure. Several studies are being performed to optimize thrombolytic treatment and to prevent coronary reocclusion after successful thrombolysis. As thrombosis also plays a major role in unstable angina, the effects of anti-thrombotics are studied in these patients for the prevention of myocardial infarction and heart failure. In the human, coronary blood flow and flow bypass grafts in relation to function is studied using non-invasive techniques such as MRI. Flow reserve, can be obtained with MRI, giving much better functional information than angiography. Local perfusion experiments will be related to local function studies using MRI-tagging technique and local metabolic studies using PET and radiolabelled nutrients. The combination of these techniques will give a wealth of information not obtainable otherwise.

Related organisations

Related people

Researcher Dr. E.N.T.P. Bakker
Researcher Dr. W.L.F. Bedaux
Researcher Dr. A.M. Beek
Researcher Dr. J.W.M. ter Berg
Researcher H.M.M. van Beusekom
Researcher Drs. W.J. Bos
Researcher R. Braakman
Researcher Prof.dr. D.L. Brutsaert
Researcher Dr. W.R.M. Dassen
Researcher Dr. M.A. Dijkman
Researcher Dr. P.A. Dijkmans
Researcher Dr. W.G. van Dockum
Researcher Prof.dr. P.A.F.M. Doevendans
Researcher Dr. R.T. van Domburg
Researcher D. Gattullo
Researcher C. Heymes
Researcher Dr. M.B.M. Hofman
Researcher Dr. C.J.M. Kerkhof
Researcher Dr. R. Nijveldt
Project leader Dr. J.G.F. Bronzwaer
Project leader Dr. C.C. de Cock
Project leader Prof.dr. C.J.A. van Echteld
Project leader Prof.dr. R.M. Heethaar
Project leader Dr. O. Kamp
Project leader Prof.dr. J.J. de Lange
Project leader Dr. J.T. Marcus
Project leader Dr. R.J.P. Musters
Project leader Prof.dr. A.C. van Rossum
Project leader Prof.dr. G.J. Scheffer
Project leader Dr. P. Sipkema
Project leader Dr. M. Sprenger
Project leader Dr. G. Veen
Project leader Prof.dr. C.A. Visser
Project leader Prof.dr. F.C. Visser
Project leader Prof.dr. N. Westerhof

Classification

A70000 Public health and health care
D21200 Biophysics, clinical physics
D23220 Internal medicine

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