The role of post-ischaemic reperfusion in the development of microvascular incompetence and ultrastructural damage in the myocardium

Abstract

To determine the contribution of oxygenated reperfusion to the development of myocardial microvascular incompetence and ultrastructural damage following ischaemia, isolated buffer perfused rat hearts were subjected to either temporary (n = 15) or permanent (n = 15) ischaemia for 15, 30 or 45 minutes. The temporarily ischaemic hearts were reperfused for 5 min with oxygenated Krebs Henseleit buffer. All hearts were then fixed by perfusion fixation with nitrogen-bubbled glutaraldehyde. The transmural development of microvascular incompetence was determined quantitatively by scanning electron microscopy using nuclear track photographic emulsion as an intravascular marker of competent capillaries, and ultrastructural damage was examined by transmission electron microscopy. Thirty or more minutes of ischaemia where required to significantly reduce the mean density of competent capillaries in the subendocardial third of the left-ventricular wall. Such ischaemic myocardium contained relatively normal, open unobstructed vessels, indicating that the microvascular incompetence arising during ischaemia per se was not due to ultrastructural change in the capillaries. Subendocardial myocardium reperfused following 15 min ischaemia also showed little ultrastructural change, but did show a significant reduction in the density of competent capillaries. However, reperfusion of more severely ischaemic myocardium resulted in obvious ultrastructural damage as well as significant further reduction in capillary competence. These findings demonstrate that oxygenated reperfusion of ischaemic myocardium paradoxically results in the further development of microvascular incompetence and, in severely ischaemic myocardium, also to additional ultrastructural damage.