Native Coronary Collateral Microcirculation Reserve in Rat Hearts

Abstract

Background We occasionally noticed that native collateral blood flow showed a recessive trend in the early stages of acute myocardial infarction in rats, which greatly interferes with the accurate assessment of native collateral circulation levels. Here, we sought to recognize the coronary collateral circulation system in depth, especially the microcirculation part, on this basis. Methods and Results In this study, we detected native collateral flow with positron emission tomography perfusion imaging in rats and found that the native flow is relatively abundant when it is initially recruited. However, this flow is extremely unstable in the early stage of acute myocardial infarction and quickly fails. We used tracers to mark the collateral in an ischemic area and a massive preformed collateral network was labeled. The ultrastructures of these collateral microvessels are flawed, which contributes to extensive leakage and consequent interstitial edema in the ischemic region. Conclusions An unrecognized short‐lived native coronary collateral microcirculation reserve is widely distributed in rat hearts. Recession of collateral blood flow transported by coronary collateral microcirculation reserve contributes to instability of native collateral blood flow in the early stage of acute myocardial infarction. The immature structure determines that these microvessels are short‐lived and provide conditions for the development of early interstitial edema in acute myocardial infarction.

Coronary Collateral Microcirculation Reserve Becomes Vestigial with Aging

“…In the early stage of AMI, the change in the number of open CCMR vessels showed a parabolic trend, resulting in instability of perfusion blood flow in the ischemic area. When the LAD was ligated for 5 min, the CCMR vessels were almost completely open [1]. The lectin-labeled vessels (green) of the same month-old rats in the 4-h group were reduced by approximately 60% compared with the 5-min group (Fig.…”

“…Coronary collateral microcirculation reserve (CCMR), which is a native and potential vessel in the adult healthy rat heart, is recruited immediately after acute myocardial infarction (AMI). CCMR can provide transient blood flow for the ischemic myocardium to prevent or reduce ischemic myocardium injury [1-4].…”

“…Other studies in mice demonstrated that aging was accompanied by a progressive loss of collateral number and diameter, resulting in more severe ischemic tissue injury [9]. Our previous study in rats suggested that the number of CCMR vessels was sizeable [1], but it is not clear whether the number and structure of CCMR change with aging.…”

PEDF Induces Native Coronary Collateral Microcirculation Remodeling in a Manner Similar to That of FSS Through Activing Canonical and Non-canonical Notch1 Signaling Pathway Simultaneously

“…During AMI, a large number of CCMR vessels were recruited to regulate coronary blood flow and myocardium perfusion. However, our further research showed that CCMR vessels of normal adult rats have natural defects in structure, as indicated by discontinuous basement membranes, less vascular endothelial cadherin (VE-cadherin) assembly and greater permeability [6]. VE-cadherin, one of the proteins forming the adherens junctions, plays an important role in maintaining vascular integrity and stability [7][8][9].…”

“…In order to explore the relationship between PEDF induced vascular remodeling and the Notch1 signaling pathway in vitro, we established the cardiac explant angiogenesis model as previously described [6,28]. Put simply, we cut and rinsed the cardiac explants (1-2mm 3 ) from neonatal Sprague-Dawley rats (1-3 days old, weighing 6.00.5 g).…”