Microvascular coronary collateral vessels

Abstract

In normal human hearts, arterial collaterals are rare, but often develop during coronary disease. These collaterals can limit or even prevent myocardial infarction. Microvascular coronary collaterals have only recently been documented, and their potential clinical significance is poorly appreciated. We employed a retrograde flow procedure to examine collateral flow in canine hearts with well-developed collateral vessels secondary to gradual coronary artery obstruction. To perform the retrograde flow procedure, the coronary artery was cannulated distal to its obstruction and allowed to drain at atmospheric pressure. Radioactive microspheres were injected systemically to measure regional blood flow before and during retrograde flow diversion. A large volume of non-divertible collateral flow indicated that significant collateral flow entered the collateral-dependent region through microscopic pathways. In a related study, we extensively embolized collateral-dependent coronary vasculature with 13 µm diameter microspheres. After embolization, retrograde flow from this region increased by 43%, further demonstrating the presence of functional microvascular collaterals. The presence of microvascular collaterals is suggestive of a border zone of intermediate perfusion surrounding acutely ischemic myocardium. To study this zone, we simultaneously injected differently colored, 10-12 µm microspheres into normally perfused coronary arteries of in situ, working canine hearts. In 40 µm myocardial sections, terminal arterioles containing microspheres of both colors were frequently found at the interface of the perfusion fields. The width of this boundary watershed zone was 3.2±0.6 (SD) mm. When microspheres of a third color were injected after occlusion of one of the arteries, the boundary watershed zone expanded by 48%. Clearly, microvascular collaterals can provide blood flow to the periphery of an ischemic region. Since this perfusion interface was labile, it might be amenable to pharmacological interventions to increase flow to the periphery of acutely ischemic myocardium and thereby limit infarct size. In 2016, van Lier et al. used high resolution, three dimensional episcopic fluorescent imaging to analyze the coronary microcirculation. In normal human hearts, the median diameter of intercoronary collaterals was 94 µm with an interquartile range of 80-107 µm. Most of these collaterals were too small to be detected by conventional imaging technics. Thus, with obstruction of a proximal coronary artery by atherosclerotic disease, microscopic as well as macroscopic collateral vessels can provide a critical source of arterial blood to ischemic myocardium. Flow from microscopic collateral vessels would most effectively supply the periphery of the ischemic region and might limit its expansion. Furthermore, as coronary disease develops, microscopic collaterals may enlarge by the process of arteriogenesis to become higher capacity conduits. Even in the absence of coronary occlusive disease, microscopic collaterals could have a vital role in protecting microscopic regions of myocardium from microemboli entering the coronary circulation. Сonclusion. There is mounting functional and histological evidence of microscopic collaterals in the normal heart and in hearts with chronic coronary artery obstruction. Further research will more clearly demonstrate the functional importance of these vessels.