Muscle Cell Function Laboratory - Professor David G. Allen

 

Heart attacks and the Na/H exchanger Lactic acid accumulates in the ischaemic heart and the removal of the associated protons on the Na/H exchanger causes Na loading. This in turn causes excessive Ca loading which is a major cause of myocardial damage. Understanding of this pathway has led to a clinical trial in which Na/H exchange inhibitors are used in the treatment of heart attacks. Our laboratory has been exploring the ionic mechanism during and after ischaemia and we have shown that up- and down- regulation of the exchanger occur during and after ischaemia and contribute to the heart's resistance to ischaemia. Very recently we have extended these ideas by showing that combination of a mitochondrial potassium channel opener with a Na/H exchanger inhibitor can allow complete functional recovery after a period of ischaemia from which there is normally little recovery. We have also found that angiotensin release from heart cells modulates the activity of the Na/H exchanger and offers another therapeutic direction for treating heart attacks. We believe that within the next few years these approaches will lead to more effective treatment of hearts which have been affected by long periods of ischaemia, for instance during transplantation, cardiac surgery or heart attacks.