TARGETING ISCHEMIA - CELL SWELLING AND DRUG EFFICACY

Myocardial ischaemia can precipitate fatal arrhythmia, the leading cau se of mortality in the western world. During ischaemia, cardiac myocyt es swell rapidly. Such changes in cell volume radically alter the elec trophysiology of these cells. Ischaemia also alters the potency of ant iarrhythmic drugs, with the effectiveness of some antiarrhythmics bein g diminished. Conversely, the idea I antiarrhythmic would be 'switched on' by ischaemia. As well as making the drug more potent, this would minimize unwanted side-effects by targeting diseased tissue alone. In this article, Anthony Wright and Sian Rees discuss possible strategies for developing 'ischaemia-selective' antiarrhythmics. To date, resear ch has focused on potentiation of antiarrhythmic action by membrane de polarization, as occurs during ischaemia. The authors suggest that cel l swelling alters drug efficacy and propose that this could represent a new way of targeting ischaemia.