Myocardial oedema: a preventable cause of reperfusion injury?

Abstract

Myocardial ischaemia increases cellular and extracellular osmolarity, alters membrane permeability to ions and causes moderate cell swelling and interstitial oedema. Ischaemia also reduces the mechanical resistance of the sarcolemma of myocytes, probably as a result of proteolytic digestion of the connections between cell membrane and the cellular scaffold. During reperfusion, the abrupt normalisation of extracellular osmotic pressure results in marked osmotic cell swelling. In the clinical situation, the ability of mechanical stress imposed by cell swelling to disrupt the weakened sarcolemma of viable myocytes during reperfusion has not been definitively established. Observations demonstrating the important role of mechanical stress caused by contraction and cell to cell interaction in myocyte necrosis support the hypothesis that osmotic cell swelling may actually produce lethal reperfusion injury. This hypothesis has been investigated by analysing the effect of hyperosmotic reperfusion with mannitol on final infarct size after coronary occlusion. Studies using highly hyperosmotic reperfusion after relatively short periods of ischaemia have yielded positive results, while studies using intravenous mannitol at the time of reperfusion, and more closely resembling clinical situations, have failed to detect any beneficial effect. Myocardial oedema could also contribute to postischaemic functional derangements, such as reperfusion arrhythmias and stunning, and could modify the passive mechanical properties of the infarcts and alter ventricular remodelling. Interventions aimed to limit myocardial oedema will probably not play a role as a co-adjuvant therapy in patients with acute myocardial infarction receiving thrombolytic treatment. However, they should probably form part of controlled reperfusion strategies to be evaluated in patients with acute myocardial infarction in whom reperfusion is accomplished by percutaneous transcoronary angioplasty or surgery.