Microvascular permeability characteristics of the isolated perfused ischemic rat heart

Isolated perfused rat hearts were used to assess the effects of ischemia on coronary microvascular permeability. Small molecules (sorbitol and sucrose) and a large molecule (bovine albumin) were used as indicators of capillary permeability. Transcapillary fluxes of small molecules and albumin were assessed by the indicator-dilution and tissue sampling techniques, respectively. Transcapillary flux of sorbitol and sucrose were directly dependent on coronary flow and did not reflect increased capillary permeability induced by Ca 2+-free perfusion. Albumin flux exhibited only a slight flow dependency and was increased by Ca 2+-free perfusion and histamine. In hearts made severely ischemic for 20 min and moderately ischemic for 2 h and then reperfused, albumin flux was increased by 100 and 200%, respectively. In contrast, sorbitol flux was not altered in post-ischemic hearts. Concomitant with the increase in albumin flux, there was tissue edema which was confined to the interstitial space. This water represented an increase of about 20% of the interstitial space of control hearts. These studies demonstrate that small molecules may not be useful indicators of changes in microvascular integrity and that ischemia increases microvascular permeability which leads to tissue edema.