| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Ann Thorac Surg 1995;60:1740
© 1995 The Society of Thoracic Surgeons
Cardiothoracic Surgery Research Laboratory, Rm A-827, Department of Cardiothoracic Surgery, New York Hospital-Cornell Medical Center, 525 E 68th St, Box 378, New York, NY 10021
Emphasis on the hematologic effects of cardiopulmonary bypass (CPB) has traditionally been placed on platelets, white cells, and the various inflammatory cascades, but it should not be forgotten that the major component of blood is the red cell. Typically during and immediately after CPB one quarter to one third of a patient's red cell mass is lost, even with maximum intraoperative and postoperative salvage efforts. A significant portion of this loss occurs during CPB, as a result of foreign surface shear stresses, interaction with complement and other mediators of the inflammatory response, and direct mechanical trauma from connectors, tubing bifurcations, occlusive pumps, and cell salvage apparatus. Red cells contain the body's largest pool of iron in the form of hemoglobin, as well as antioxidant power in the form of glutathione. These red cell constituents are released into plasma when red cells are damaged or destroyed during cardiopulmonary bypass. What are the consequences of this release? Applying their experience in free radical biochemistry, Pepper, Mumby, and Gutteridge suggest that one of the very important consequences may be an increase in production of highly reactive free radical species.
Oxygen free radical--mediated protein damage and cell membrane breakdown has been implicated as one of the primary mechanisms by which cells and tissues are damaged during reperfusion. Through well-established chemical reactions, elemental iron can both increase free radical formation and convert mildly toxic species to highly toxic species. Because of its potentially damaging effects, in the normal healthy human all iron is either in use in heme-containing molecules or is bound by a system of iron transport and storage proteins. Only in certain disease states, such as the chronic hemolytic anemias, is free iron found, this typically being attributable to the presence of excessive iron that overloads the iron-binding system.
During CPB, hemoglobin released from damaged red cells is acted on by hydrogen peroxide (from activated neutrophils), releasing free redox reactive forms of iron into the bloodstream. Pepper and associates demonstrate that in a majority of cases this free iron can be appropriately sequestered by the body's iron-binding system. Over time, however, as increasing red cell damage and loss occurs, free hemoglobin and iron accumulate. In fact, Pepper and associates found that approximately 20% of patients went into an iron overload state during the period that extended from cross-clamp removal to protamine administration-a period that corresponds with myocardial reperfusion.
Paradoxically, exacerbating the potential adverse effects of free redox reactive iron during myocardial reperfusion may be the system designed to combat oxidative damage. Glutathione is also released by red cells destroyed and damaged during CPB, and adds to the total pool of free radical--scavenging plasma thiols. Although plasma thiols and other antioxidant species have been shown in animal models to reduce measures of oxidative damage during myocardial reperfusion and improve myocardial functional recovery, the effects clinically have been less clear. Pepper and associates suggest that one possible explanation may be found in basic free radical biochemistry. The normally antioxidant species, such as glutathione, can react with the excessively high levels of free iron found in the blood during myocardial reperfusion to paradoxically increase formation of highly toxic and damaging free radical species. To derive benefit from naturally occurring antioxidant species during and after CPB, as well as from endogenously supplemented antioxidant myocardial reperfusion formulations, it may, therefore, be essential to eliminate free reactive iron from the blood perfusing the heart. This provides a clear rationale for the use of iron chelators during myocardial reperfusion, particularly when antioxidant supplementation strategies are applied.
As Pepper and associates demonstrate, however, it is a minority of patients who experience overload of the endogenous iron binding system, and so it may be a minority of patients who stand to benefit from iron chelation therapy during and after CPB. Those patients undergoing continuous warm heart operations may be at particular risk for iron-mediated free radical injury, as not only is red cell damage and release relatively greater, but the heart is continually bathed in these released products. Further studies documenting other risk factors for the development of iron overload may help in the more appropriate selective application of this therapy, should it prove to be effective.
The importance of this study by Pepper and associates lies in their recognition and documentation of the existence of a set of circumstances-unique to cardiopulmonary bypass operations-that may act to injure the heart. It now remains to be proven that free iron and plasma thiols do in fact cause such injury, and that treatment with iron-chelating agents protects against this injury. Their study serves to remind us of the very complex nature of the interaction between the human body and the cardiopulmonary bypass apparatus, and of the advances in the understanding of this interaction that can be gained by cooperation between the scientific disciplines.
Related Article
Ann. Thorac. Surg. 1995 60: 1735-1740.
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| ANN THORAC SURG | ASIAN CARDIOVASC THORAC ANN | EUR J CARDIOTHORAC SURG |
| J THORAC CARDIOVASC SURG | ICVTS | ALL CTSNet JOURNALS |
