role of membrane phospholipids in arrhythmogenesis: from basic research to possible clinical application

ABSTRACT

The work from our laboratory and others presented above has helped to form the concept that at least some of the functional abnormalities of the ischemic heart are the consequence of abnormal lipid metabolism. It was postulated that drugs which circumvent such changes should have some protective effects. In fact, certain amphiphilic drugs such as AM, CQ and CZ have been shown by us and others to reduce structural and functional abnormalities both in animal experiments and in clinical treatment. This strongly suggests that lipid abnormalities contribute to myocardial malfunction. Whether the beneficial effects of these drugs lie solely in their ability to inhibit phospholipases is difficult to prove, since all these agents also affect a large number of other cellular functions. This question can best be answered by finding or by synthesizing a phospholipase-specific inhibitor and by determining whether this agent alone is capable of reducing the structural and functional abnormalities caused by ischemia. Given the calibre and scope of cardiac research today, it is expected that such an agent will become available in the not too distant future