The oxygen free radical system: from equations through membrane-protein interactions to cardiovascular injury and protection.
Highly toxic oxygen radicals and their metabolites have been implicated in the pathogenesis of ischaemia/reperfusion injury. These reactive oxygen species include the superoxide anion, hydrogen peroxide, hydroxyl radical, and singlet oxygen. The central theme of this review is first to discuss the basic mechanisms of free radical generation from various potential sources, to point out and emphasise the growing importance of the role of singlet oxygen, and then to discuss in depth membrane-protein interactions that ultimately lead to myocardial damage and dysfunction. With this background, we highlight several novel therapeutic strategies aimed at interrupting the oxygen free radical mediated component of ischaemia/reperfusion injury. It is hoped that this thesis will then serve as a future impetus to challenge these hypotheses and further build on this truly unique system that has assumed such an important role in the pathophysiology of myocardial ischaemia/reperfusion and inflammation. "To those of us who are humbly exploring the mysteries of science, we must project our findings and model our systems. For if correct, we have made a small contribution and, if wrong, we have forced others to eventually think." A V Hill, on the occasion of the 50th anniversary of E H Starling's Linacre lecture (University College, London, 1968).
Kukreja
R C
RC
Department of Medicine, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Hess
M L
ML
D000975:Antioxidants / Q000627:therapeutic use; D002462:Cell Membrane / Q000378:metabolism*; D005609:Free Radicals / Q000378:metabolism; D006639:Histidine / Q000627:therapeutic use; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D010100:Oxygen / Q000378:metabolism*
D000975:Antioxidants; D005609:Free Radicals; D008565:Membrane Proteins; D006639:Histidine; D010100:Oxygen