24 - REDUCED CAPILLARY DENSITY IN THE MYOCARDIUM OF THE PATIENTS WITH KD HISTORY

Background: Endothelial dysfunction and reduced capillary density (capillary rarefaction) could lead to coronary microvascular dysfunction and myocardial ischemia. The histology of autopsies from adults who had KD in childhood revealed diffuse, bridging fibrosis in the myocardium, which was unlikely to be due to thrombosis of the epicardial coronary arteries. It is unclear how or why this fibrosis occurs. In the LCWE KD mouse model, reduced capillary density and increased fibrosis in the myocardium were reported long after induction of vasculitis. Electron microscopic study of endomyocardial biopsies from patients after KD showed dilated microvasculature with fresh thrombus suggesting disturbed microvascular circulation in these patients. To understand the etiology of myocardial fibrosis in KD patients, we studied capillary rarefaction in KD autopsies.

Methods: To reduce the influence of different fixation conditions, we tested antibodies to four different endothelial cell (EC) markers: CD31, CD34, thrombomodulin, and Factor VIII in a pilot study. To analyze capillary density, we studied the myocardium from five autopsy cases with a KD history (interval from KD onset to autopsy: 10 days to 12 y), and non-KD control cases (age 5y and 13y). Fields were chosen from three different areas: endocardium, epicardium, and middle (x200 magnification). Positively stained cells were counted using QuPath software.

Results:  Of the four antibodies tested, anti-thrombomodulin yielded the most consistent staining intensity and the highest specificity for EC. In the myocardial sections from the KD autopsies, varying levels of inflammation and fibrosis were seen.  Staining with anti-CD31 and anti-thrombomodulin antibodies suggested diminished capillary density in KD myocardial sections compared to controls (Figure). Detailed capillary density analysis by myocardial region is in progress.

Conclusion: Investigation of capillary rarefaction in the myocardium from age-matched controls and KD autopsies with different intervals between disease onset and death is in progress. These studies may shed light on the function of the myocardial microcirculation and the genesis of myocardial fibrosis following KD.