Endothelial permeability as factor affecting reperfusion damage.

The aim of this study was to evaluate the effects of endothelial permeability dysfunction on reperfusion damage. We used isolated working rat hearts subdivided into three groups: A) Control hearts perfused in working heart mode, B) Hearts subjected to 10 min. global ischemia, C) Hearts subjected to 20 min. global ischemia. Hemodynamic parameters, CPK and LDH release, reperfusion edema (expressed as % gain and ratio) and cellular damage (immunoperoxidase labeled anti-LDH Ab) were assessed. Endothelium permeability was evaluated using FITC-albumin diffusion technique. Cellular damage and endothelial permeability evaluation was performed with a computerized image analysis system. A significant ischemia-time related functional impairment was observed in B and C groups (at 55 min., coronary flow: A: 12 ± 2.3 ml/min, B: 9 ± 2.1 ml/min. p<0.05 vs A, C: 7.3 ± 3 ml/min, p<0.001 vs A and p<0.05 vs B) associated to a significant increase of myocardial edema (A: 9 ± 2.5%, B: 16 ± 3%, p<0.01 vs A, C: 28 ± 6%, p<0.001 vs A and p<0.01 vs B) and myocardial enzymatic release. LDH tissue deposition significantly increased in B and C groups (p<0.02 and p<0.001 vs A respectively). FITC-albumin diffusion was significantly higher in ischemic hearts and related to ischemia severity with an interstitial diffusion in perimyocytic and perivascular space. Linear positive correlations were detected between LDH deposition and heart weight gain (r: 0.80, p<0.001) and between CPK release and heart weight gain (r: 0.93, p<0.001). Our data evidenced that ischemia-induced endothelial permeability changes, by affecting microcirculation homeostasis, are directly related to reperfusion damage.