Porcine coronary collateral formation in the absence of a pressure gradient remote of the ischemic border zone

Abstract

van den Wijngaard JP, Schulten H, van Horssen P, ter Wee RD, Siebes M, Post MJ, Spaan JA. Porcine coronary collateral formation in the absence of a pressure gradient remote of the ischemic border zone. Am J Physiol Heart Circ Physiol 300: H1930 -H1937, 2011. First published March 11, 2011 doi:10.1152/ajpheart.00403.2010.-In the current paradigm on coronary collateral development, it is assumed that these vessels develop consequentially from increased fluid shear stress (FSS) through preexisting collateral arteries. The increased FSS follows from an increase in pressure gradient between the region at risk and well-perfused surroundings. The objective of this study was to test the hypothesis that, in the heart, collateral connections can form in the absence of an increased FFS and consequentially at any depth and region within the ventricular wall. In Yorkshire pigs, gradual left circumflex coronary artery occlusion was obtained over 6 wk by an ameroid constrictor, whereas the control group underwent a sham operation. Hearts were harvested and subsequently processed in an imaging cryomicrotome, resulting in 40-m voxel resolution threedimensional reconstructions of the intramural vascular vessels. Dedicated software segmented the intramural vessels and all continuous vascular pathways containing a collateral connection. In the ameroid group, 192 collaterals, 22-1,049 m in diameter, were detected with 62% within the subendocardium. Sixty percent of collaterals bridged from the left anterior descending artery to left circumflex coronary artery. A novel result is that 25% (n ϭ 48) of smaller-radius collaterals (P ϭ 0.047) connected with both origin and terminus in the nontarget area where perfusion was assumed uncompromised. In the porcine heart, collateral vessels develop not only in ischemic border zones with increased FSS but also away from such border zones where increased FSS is unlikely. The majority of collaterals were located at the subendocardium, corresponding to the region with highest prevalence for ischemia. imaging cryomicrotome; collaterals; ischemia; remodeling; fluid shear stress STIMULATING CORONARY COLLATERAL formation by neovascularization may serve as a last therapeutic resort for patients that cannot be successfully revascularized by coronary artery bypass surgery or percutaneous coronary intervention. However, further development of this therapeutic modality requires more detailed information on the mechanisms of collateral formation.There are differences of opinion whether in the porcine heart collaterals grow de novo, i.e., through angiogenesis stimulated by ischemia, or from innate nonfunctional collaterals that are already present, i.e., arteriogenesis stimulated by shear stress (23,29). In the hindlimb occlusion model, collaterals growing in the nonischemic area proximal to the experimentally induced flow obstruction clearly indicates the role of increased fluid shear stress (FSS) in outward remodeling (7, 9, 23). In the heart, however, regions of ischemia are intertwined with areas of inc...

Detection and quantification methods of monocyte homing in coronary vasculature with an imaging cryomicrotome

“…To identify collateral connections, seed points were assigned to major vessels and contiguous connectivity was probed between major vessels following all pathways defined by connecting segments. When the major vessels were connected the smallest vessel in the segmented loop was defined as a collateral connection [11,13].…”

“…The objective of this study was to demonstrate the feasibility of the imaging cryomicrotome [10][11][12][13] to visualize monocytes at μm resolution on a 3D level, in conjunction with the coronary microvascular network. This imaging modality has been successfully employed in the assessment of vascular adaptation due to cryoablation [14], and in the detection of coronary collateral vessels [10][11][12][13], but not in conjunction with monocyte detection.…”

“…This imaging modality has been successfully employed in the assessment of vascular adaptation due to cryoablation [14], and in the detection of coronary collateral vessels [10][11][12][13], but not in conjunction with monocyte detection. We utilized different animal models and examined various fluorescent probes for cellular imaging, with a focus on monocytes.…”

Model-Based Vasculature Extraction From Optical Fluorescence Cryomicrotome Images

“…1 bottom). The heart processing and imaging in the cryomicrotome is according to standard procedures developed at the Department of Biomedical Engineering and Physics, Academic Medical Center, University of Amsterdam ( [46], [53]). …”

“…vasculatures of larger animal models such as pig, dog, and human (deceased) with the high voxel resolution of 50 m (isotropic). Of specific relevance to the current work and the development of the coronary vascular models outlined above are recent studies that have successfully been employed for ex vivo visualization of whole-organ vascular trees (Lagerveld et al [47], van den Wijngaard et al [48], van Horssen et al [49], [50], Lagerveld et al [51], van den Wijngaard et al [52], [53]). …”