Beck and back: A paradigm change in coronary sinus interventions—pulsatile stretch on intact coronary venous endothelium
Received 22 July 2006; received in revised form 20 November 2006; accepted 28 December 2006.
Objectives
Strategies to recover myocardium in therapeutically unresponsive patients are again under scrutiny, including techniques developed in the pioneering days of cardiothoracic surgery such as retroperfusion via the coronary sinus—the Beck procedure. An underestimated aspect of retroperfusion is the formation of new vessels. This early observation of neoangiogenesis may be an important mechanism in observed benefits. We hypothesized that periodic pressure elevation in coronary veins induces an analogy to shear stress angiogenic pulses by activating venous endothelium. Pulsatile stretch on venous endothelium can be achieved easily by a pressure-controlled intermittent balloon blockade of the coronary sinus outflow.
Methods
Three hours of myocardial ischemia was induced in 12 pigs. Pressure-controlled intermittent coronary sinus occlusion was applied in 6 animals 15 minutes after occlusion of the left anterior descending coronary artery. Postmortem myocardial specimens were taken, and heme oxygenase-1, vascular endothelial growth factor gene expression, and hypoxia-induced factor activity were measured.
Results
As compared with controls, treated animals released an angiogenic pulse by a 4-fold increase of heme oxygenase-1 gene expression in the infarct area (P < .001), together with a 2.5-fold enhanced transcription of vascular endothelial growth factor in the infarct (P < .006), border (P < .002), and remote (P < .02) areas, whereas hypoxia-induced factor activity was similar in both groups. A significant correlation (P < .01) of the achieved coronary sinus pressure elevation and gene expression was found.
Conclusions
Mechanotransduction of pulsatile stretch on coronary venous endothelium by pressure-controlled intermittent coronary sinus occlusion induces heme oxygenase-1 and vascular endothelial growth factor gene expression, leaving the ischemic pathway of the hypoxia-induced factor activity unchanged. This cascade of molecular events closes the argument gap to historical reports of the Beck procedure on revascularization and myocardial salvage.
aDepartment of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria
dDepartment of Internal Medicine 2, Division of Cardiology, Medical University of Vienna, Vienna, Austria
cInstitute of Biomedical Research, Medical University of Vienna, Vienna, Austria
eCore Unit for Medical Statistics and Informatics, Section of Clinical Biometrics, Medical University of Vienna, Vienna, Austria
bTU BioMed, University of Technology, Vienna, Austria
fCarinthia University of Applied Sciences, Medical Information Technology, Klagenfurt, Austria.
Address for reprints: Werner Mohl, MD, PhD, Medical University of Vienna, Department of Cardiothoracic Surgery, Waehringer Guertel 18-20, 1090 Vienna, Austria.
This work was supported by the “Fonds zur Foerderung der wissenschaftlichen Forschung P 13274-Med,” the “Society of Coronary Sinus Interventions,” the Federal Ministry of Traffic, Innovation and Technology (BMVIT) GZ609.637/0002-III/I2/2004, the Ludwig Boltzmann Institute for Cardiosurgical Research, and the Austrian Research Center Seibersdorf.
ABSTRACT