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The human coronary collateral circulation: Assessment, pathogenesis, pathophysiology and therapeutic promotion

English title The human coronary collateral circulation: Assessment, pathogenesis, pathophysiology and therapeutic promotion
Applicant Seiler Christian
Number 124848
Funding scheme Project funding
Research institution Klinik und Poliklinik für Kardiologie Departement Herz und Gefässe Universitätsklinik, Inselspital
Institution of higher education University of Berne - BE
Main discipline Clinical Cardiovascular Research
Start/End 01.07.2009 - 30.06.2012
Approved amount 402'209.00
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Keywords (10)

coronary circulation; coronary artery disease; collateral circulation; angiogenesis; arteriogenesis; growth factors; bradycardia; external counterpulsation; granulocyte colony stimulating factor; ivababradine

Lay Summary (German)

Lead
Lay summary
In industrialisierten Ländern sterben die Leute am häufigsten an Herz-/Kreislaufkrankheiten. Die koronare Herzkrankheit spielt dabei die grösste Rolle, d.h., etwa jede vierte Person stirbt an oder nach einem Herzinfarkt. Die koronare Herzkrankheit zeichnet sich aus durch eine Arterienverkalkung der Herzkranzgefässe mit Einengungen und Verschlüssen. Der Verschluss eines Herzkranzgefässes führt zu einem Herzinfarkt sofern nicht Blut via neu gebildete Gefässe (Kollateralgefässe) zum blockierten Gefäss fliesst. Wenn solche natürlichen Bypasses gut ausgebildet sind, gibt es trotz Koronararterien-Verschluss keinen Infarkt und somit keine damit verbundene Sterblichkeit. Das vorliegende ist die Fortsetzung eines Projekts zu diesem Thema, welches seit 13 Jahren bearbeitet wird und alle Aspekte der Versorgung des menschlichen Herzens mit Kollateral-Gefässen untersucht. Insbesondere wird bei diesem Projekt nach Methoden gesucht, wie man die Kollateral-Gefässe beim Herz therapeutisch verbessern kann. Damit sucht man nach einer alternativen Methode zur Bypassoperation oder Ballonbehandlung bei Patienten mit koronarer Herzkrankheit. Um dieses Ziel zu erreichen, muss man die Funktion der Kollateralgefässe möglichst genau messen können, d.h. deren Fähigkeit Blut zu befördern muss erfassbar sein. Diese Methode wurde im Rahmen dieses Projekts entwickelt und wird oft verwendet. Zudem wird erforscht, unter welchen Bedingungen beim Menschen ein Umgehungs- oder Kollateralkreislauf am Herz natürlicherweise gut oder nur eingeschränkt ausgebildet ist. Dies könnte Hinweise auf mögliche Therapieansätze der Kollateralzirkulation liefern.
Direct link to Lay Summary Last update: 21.02.2013

Responsible applicant and co-applicants

Employees

Publications

Publication
Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis
Meier Pascal, Indermuehle Andreas, Pitt Bertram, Traupe Tobias, de Marchi Stefano F, Crake Tom, Knapp Guido, Lansky Alexandra J, Seiler Christian (2012), Coronary collaterals and risk for restenosis after percutaneous coronary interventions: a meta-analysis, in BMC Medicine, 10(1), 62-62.
Determinants of Prognostically Relevant Intracoronary Electrocardiogram ST-Segment Shift During Coronary Balloon Occlusion
de Marchi Stefano Fausto, Streuli Sabina, Haefeli Pascal, Gloekler Steffen, Traupe Tobias, Warncke Cornelius, Rimoldi Stefano F., Stortecky Stefan, Steck Hélène, Seiler Christian (2012), Determinants of Prognostically Relevant Intracoronary Electrocardiogram ST-Segment Shift During Coronary Balloon Occlusion, in The American Journal of Cardiology, 110(9), 1234-1239.
Letter by Gloekler et al Regarding Article, “Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic Angina: A Randomized Sham-Controlled Study”
Gloekler Steffen, Traupe Tobias, Seiler Christian (2011), Letter by Gloekler et al Regarding Article, “Enhanced External Counterpulsation Improves Peripheral Artery Flow-Mediated Dilation in Patients With Chronic Angina: A Randomized Sham-Controlled Study”, in Circulation, 123(23), 1-1.
Coronary collateral function in the transplanted heart: propensity score matching with coronary artery disease
Rutz T., Gloekler S., de Marchi S. F., Traupe T., Meier P., Eshtehardi P., Cook S., Vogel R., Mohacsi P., Seiler C. (2011), Coronary collateral function in the transplanted heart: propensity score matching with coronary artery disease, in Heart, 97(7), 557-563.
Determinants of Preformed Collateral Vessels in the Human Heart without Coronary Artery Disease
de Marchi Stefano F., Gloekler Steffen, Meier Pascal, Traupe Tobias, Steck Hélène, Cook Stéphane, Vogel Rolf, Seiler Christian (2011), Determinants of Preformed Collateral Vessels in the Human Heart without Coronary Artery Disease, in Cardiology, 118(3), 198-206.
Assessment of the Human Coronary Collateral Circulation
Traupe Tobias, Gloekler Steffen, de Marchi Stefano F., Werner Gerald S., Seiler Christian (2010), Assessment of the Human Coronary Collateral Circulation, in Circulation, 122(12), 1210-1220.
Instantaneous coronary collateral function during supine bicycle exercise
Togni Mario, Gloekler Steffen, Meier Pascal, de Marchi Stefano F., Rutz Tobias, Steck Hélène, Traupe Tobias, Seiler Christian (2010), Instantaneous coronary collateral function during supine bicycle exercise, in European Heart Journal, 31(17), 2148-2155.
Safety of Diagnostic Balloon Occlusion in Normal Coronary Arteries
Gloekler Steffen, Traupe Tobias, Meier Pascal, Steck Hélène, de Marchi Stefano F., Seiler Christian (2010), Safety of Diagnostic Balloon Occlusion in Normal Coronary Arteries, in The American Journal of Cardiology, 105(12), 1716-1722.
Physical Coronary Arteriogenesis: A Human “Model” of Collateral Growth Promotion
Vogel Rolf, Traupe Tobias, Stolt Steiger Valérie, Seiler Christian (2010), Physical Coronary Arteriogenesis: A Human “Model” of Collateral Growth Promotion, in Trends in Cardiovascular Medicine, 20(4), 129-133.
Coronary collateral growth by external counterpulsation: a randomised controlled trial
Gloekler S., Meier P., de Marchi S. F., Rutz T., Traupe T., Rimoldi S. F., Wustmann K., Steck H., Cook S., Vogel R., Togni M., Seiler C. (2010), Coronary collateral growth by external counterpulsation: a randomised controlled trial, in Heart, 96(3), 202-207.
Myocardial Salvage Through Coronary Collateral Growth by Granulocyte Colony-Stimulating Factor in Chronic Coronary Artery DiseaseA Controlled Randomized Trial
Meier Pascal, Gloekler Steffen, de Marchi Stefano F., Indermuehle Andreas, Rutz Tobias, Traupe Tobias, Steck Helene, Vogel Rolf, Seiler Christian (2009), Myocardial Salvage Through Coronary Collateral Growth by Granulocyte Colony-Stimulating Factor in Chronic Coronary Artery DiseaseA Controlled Randomized Trial, in Circulation, 120(14), 1355-1363.

Associated projects

Number Title Start Funding scheme
112341 The human coronary collateral circulation: assessment, pathogenesis, pathophysiology and therapeutic promotion 01.07.2006 Project funding
141030 The Human Coronary Collateral Circulation: Assessment, Pathogenesis, Pathophysiology and Therapeutic Promotion 01.07.2012 Project funding
141030 The Human Coronary Collateral Circulation: Assessment, Pathogenesis, Pathophysiology and Therapeutic Promotion 01.07.2012 Project funding
49623 Pathogenetic, Pathophysiologic and Therapeutic Aspects of the Human Coronary Collateral Circulation Assessed by Intravascular Velocity- and Pressure-Sensors. 01.07.1997 Project funding
113888 The Role of Endothelial Cells in Human Coronary Collateral Growth 01.05.2007 Project funding
58945 The human coronary collateral circulation: Assessment, pathogenesis, pathophysiology and therapeutic promotion 01.07.2000 Project funding
112341 The human coronary collateral circulation: assessment, pathogenesis, pathophysiology and therapeutic promotion 01.07.2006 Project funding
100065 The human coronary collateral circulation: Assessment, pathogenesis, pathophysiology and therapeutic promotion 01.07.2003 Project funding

Abstract

Cardiovascular diseases are responsible for the majority of deaths in industrialized countries. The mainstay of revascularization for coronary artery disease (CAD) consists of artificially bypassing or percutaneously dilating atherosclerotic lesions. Collaterology, the comprehensive investigation in humans of naturally present bypasses between vascular areas jeopardized by CAD represents the basis for establishing a third treatment pillar for CAD aside from the mentioned ones, i.e., therapeutic promotion of collateral growth (angio- and arteriogenesis).In order to be able to test various therapeutic options for collateral growth, reliable methods to measure collateral function are mandatory. Today, the sensor-derived measurement of collateral flow index (CFI) obtained during coronary occlusion is regarded as the gold standard for human collateral assessment. During the preceding 11 years of SNF-supported research, over 1’200 invasive CFI measurements have been performed at our institution constituting the largest data base worldwide for the investigation of all aspects of the human cardiac collateral circulation. However, the following problems relating to human collateralology are still unresolved:-It is unknown whether the human coronary circulation is distensible, and if yes, how this influences pressure-derived CFI measurements. -Collateral assessment should be non-invasive.-Clinical determinants of pre-formed functional collaterals in humans without CAD are unknown.-The arteriogenic effects of acute fluid shear stress increase in humans are unknown.-The acute response to isometric physical exercise on collateral blood flow is unknown.-The long-term effect of chronically applied granulocyte-colony stimulating factor on CFI is unknown-The effect of inducing selective sinus bradycardia on CFI is unknown.-The effect of augmenting coronary sinus pressure in humans on CFI is unknown.Accordingly, it is the goal of the upcoming 3-year period of the project on human collaterology supported by the SNF for the past 12 years to perform the following investigations in approximately 450 individuals without and with chronic stable CAD:A. Assessment of collaterals:-Distensibility of the human coronary circulation-ECG signs of myocardial ischemia and electrical instability in collateral assessment (data base analysis)-MCE-derived relative myocardial blood volume during systole and diastole for collateral assessmentB. Pathogenetic aspects of collaterals: -Heart transplantation as a determinant of collateral function-Predictors of pre-formed coronary collaterals (data base analysis)-Safety of occlusion of normal coronary arteries (data base analysis)C. Pathophysiology of collaterals: -Acute arteriogenic effects of external counterpulsation -MCE-derived coronary collateral blood flow changes induced by supine bicycle ergometry-Effect of coronary occlusion corrected for collateral function on ECG QTc timeD. Therapeutic promotion of collaterals: -Pegfilgrastim and coronary collateral growth-Ivabradin and coronary collateral growth-Effect of coronary sinus pressure changes on collateral functionMCE=myocardial contrast echocardiography
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