Prof.  Xiao-Ming  Gao
Xinjiang Medical University,  China

Title: Microvascular damage following cardiac ischemia-reperfusion injury

Abstract:

Ischemic heart disease is the primary cause of heart failure and cardiac death, and blood flow restoration is the most effective treatment for myocardial ischemia. Although most patients with myocardial ischemia can achieve optimal blood flow restoration, the mortality of heart failure within one year is still as high as 38%. The sudden recovery of restored blood flow will cause ischemia/reperfusion (I/R) injury, and the degree of I/R injury has a profound impact on clinical prognosis and cardiac function recovery. Previous studies and treatments mostly focused on restoring blood supply and protecting myocardial cells, while ignoring the damage and role of microvessels that provide blood and nutrients to the myocardium, and the beneficial research findings were not successful for clinical translation. This fact indicates that further understanding on the pathological mechanism of I/R injury is imperative and will facilitates development of novel and more effective interventions. The essence of I/R injury is myocardial microvascular damage (MVD), which includes two aspects: (1) Microvascular obstruction (MVO) is mainly due to vascular endothelial swelling, red blood cell embolism, platelet/leukocyte adhesion and aggregation, and the formation of micro-blood thrombus, leading to no-reflow phenomenon. (2) Microvascular leakage (MVL) is mainly caused by the destruction of endothelial cell barrier, the leakage of plasma and protein from blood vessels, which leads to myocardial edema and intra-myocardial hemorrhage, and the infiltration of inflammatory cells causing local strong inflammatory reactions. The combination of MVO and MVL leads to sustained tissue damage. MVO has been widely studied, but MVL has received little attention due to the lack of methods for evaluating MVL. Our preliminary research successfully established an experimental cardiology detection and evaluation method for MVL, including chemical quantitative analysis, histological methods and nuclear magnetic resonance technology, which providing effective tools and solutions for research in this field. In the follow-up study, we adopted relevant interventions to focus on reducing MVL. Although the intervention could not reduce the myocardial infarction area, but effectively reduced the no-reflow area by 38%, decreased MVL by 56%, attenuated the regional inflammatory response, prevented the degradation of VE-cadherin, thereby inhibiting the adverse remodeling of the ischemic heart and protecting the contractile function. These findings demonstrate the significance of reducing MVD in the protection of ischemic myocardium and elicit a new perspective and potential research and intervention directions for reducing I/R damage, protecting ischemic myocardium, and improving long-term cardiac remodeling.

Key Words：myocardial ischemia/reperfusion injury，microvascular obstruction，microvascular leakage

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