Myocardial interstitium plays an important role in the regulation of cardiac function compared with myocytes and it is actively involved in ischemia-reperfusion damage and in the acute and chronic remodelling during ischemic heart diseases. Myocardial post-ischemic oedema seems to interfere in this process. Myocardial oedema is able to induce structural alterations, to reduce myocardial function and to activate the renin-angiotensin-aldosterone system. Angiotensin II and aldosterone seem to be the cause of myocardial fibrosis that is detected during ischemic heart disease. Post-ischemic vascular permeability alterations have a similar role. In clinical conditions, ACE-inhibitors have important effects on cardioreparation and are able to improve cardiac function and reduce early and late mortality. The effects of myocardial oedema reduction (i.e. hypertonic reperfusion) on ischemia-reperfusion damage and myocardial fibrosis are still to clarify. A reduction in myocardial fibrosis may improve cardioreparation and prevent congestive heart failure, following ischemic heart disease.