Cardiac microvascular obstruction (MVO) following ischemia/reperfusion (I/R) has been well studied, but microvascular leakage (MVL) remains largely unexplored. We characterized MVL in the mouse I/R model by histology, biochemistry and cardiac magnetic resonance (CMR) imaging. I/R was induced surgically in mice. MVL was determined by administrating microvascular permeability tracer Evans blue (EB) and/or gadolinium-DTPA contrast. The size of MVL, infarction and MVO in the heart was quantified histologically. Myocardial EB was extracted and quantified chromatographically. Serial CMR images were acquired from euthanized mice to determine late-gadolinium enhancement (LGE) for a comparison with MVL quantified by histology. I/R resulted in MVL with its severity dependent on the ischemic duration and reaching its maximum at 24-48 h after reperfusion. The size of MVL correlated with the degree of LV dilatation and reduction in ejection fraction. Within the risk zone, the area of MVL (75±2%) was greater than that of infarct (47±4%, P<0.01) or MVO (36±4%, P<0.01). Contour analysis of paired CMR-LGE by CMR and histological MVL images revealed a high-degree of spatial co-localization (r=0.959, P<0.0001). These data indicate that microvascular barrier function is damaged following I/R leading to MVL. Histological and biochemical means are able to characterize MVL by size and severity while CMR-LGE is a potential diagnostic tool for MVL. The size of ischemic myocardium exhibiting MVL was greater than that of infarction and MVO, implying a role of MVL in post-infarct pathophysiology.
- myocardial infarction
- microvascular damage
- cardiac magnetic resonance imaging
- animal model
- Copyright © 2017, American Journal of Physiology-Heart and Circulatory Physiology