Microvascular Dysfunction Related to Progressive Left Ventricular Remodeling due to Chronic Occlusion of the Left Anterior Descending Artery in an Adult Porcine Heart

Abstract

Occlusion of a major coronary artery induces myocardial infarction (MI), leading to left ventricle (LV) remodeling due to progressive microvasculature dysfunction. Irreversible impairment in microvascular function has been suggested to extend from the infarcted region into the infarct-border or remote regions, depending on the time to revascularization. Our aim was to determine whether the occlusion of a major coronary artery induces microvascular dysfunction in the adjacent area perfused by intact coronary arteries using a porcine model for chronic total occlusion of the left anterior descending artery (LAD). MI was induced via an ameroid constrictor ring around the LAD in adult Göttingen pigs (Sus scrofa domesticus, n = 5). Age-matched normal pigs were treated as controls (n = 3). Cardiac magnetic resonance showed reduced systolic regional wall motion in the left circumflex (LCx) and right coronary artery (RCA) territories, with a progressively worsening motion in the infarction-adjacent area over an eight-week period. On 13 N-ammonia positron emission tomography (PET), myocardial blood flow (MBF) during hyperemia was significantly greater in the LCx and RCA territories (particularly in the infarction-adjacent area) compared to that in the LAD territory at four weeks after infarct induction. Subsequently, the flow significantly decreased, approaching that in the LAD territory at eight weeks after infarct induction. Fluoroscopy-guided pressure-wire studies showed significantly higher microvascular resistance in the LCx area at eight weeks compared to that in controls. Electron microscopy showed endothelium swelling and microvasculature disruption in areas adjacent to the LCx and RCA territories. Anterior MI caused coronary microvascular dysfunction in the adjacent area, associated with a reduced MBF and regional wall motion.

Myocardial Viability, Functional Status, and Collaterals of Patients With Chronically Occluded Coronary Arteries

“…As previously reported ( 17 ), the most specific segments including anterior, anteroseptal segments correspond to LAD, but no segments can be exclusively attributed to RCA or LCX. Additionally, Yajima et al ( 24 ) also reported myocardial scar in territories adjacent or remote to CTO territories in a chronic myocardial infarction (MI) adult porcine model and explained it by endothelium swelling and microvasculature disruption. Therefore, the variable vascular territories and extensive microvasculature injury could account for the bias of myocardial viability analysis.…”

Effects of β-carotene on glucose metabolism dysfunction in humans and type 2 diabetic rats

“…Longterm clinical observational studies on diabetes have revealed that, in addition to metabolic toxicity factors, protective factors may also protect the function and survival of cells involved in microvascular diseases through influencing blood glucose control [32][33][34]. Therefore, we also examined cardiac microvascular recruitment on the basis of the diastolic/systolic stress MBF ratio, as a novel diagnostic index with moderate diagnostic accuracy [35]. Similarly to previous studies, our study demonstrated that adding β-carotene increased MBF and significantly increased mitochondrial respiratory function (Figure 7).…”

Agreement in Left Ventricular Function Measured by Echocardiography and Cardiac Magnetic Resonance in Patients With Chronic Coronary Total Occlusion

“…These findings might result from worse ventricular functions in enrolled subjects. Due to long-term ischemic impairment, minimal infarction and restructure in local myocardium are more common in CTO patients, leading to abnormalities in cardiac structure and function ( 11 ) and affecting the myocardium mapping during measurement.…”