Hemolysis, leukopenia, a hemostatic deficit, and nonspecific systemic reactions collectively known as the postperfusion syndrome develop in patients who undergo cardiopulmonary bypass. We now report that terminal C5b-9 complement complexes are deposited on erythrocytes and polymorphonuclear neutrophilic leukocytes during cardiopulmonary bypass. Plasma samples taken from 48 unselected patients during and at the end of cardiopulmonary bypass contained raised levels of fluid-phase SC5b-9 complement complexes, indicating that the complement sequence had been activated to completion. Various degrees of overt intravascular hemolysis were observed in all the patients, and lysed erythrocyte membranes were recovered from the blood samples. Immunoassays performed with use of antibodies to C5b-9 neoantigens demonstrated the presence of C5b-9 on red-cell ghosts but not on intact erythrocytes. The appearance of ghosts carrying C5b-9 always coincided with hemolysis. Furthermore, granulocytes isolated from 20 patients during bypass were all found to carry C5b-9 complexes, whereas cells isolated before or 24 hours after surgery carried no C5b-9. The neoantigen-positive material present in detergent extracts of granulocytes sedimented in a broad peak (25 to 40 sedimentation coefficient [S]) in sucrose-density gradients, exactly as did pore-forming C5b-9 complexes. Deposition of C5b-9 on blood cells during cardiopulmonary bypass may be partly responsible for the hemolysis and may augment granulocyte activation by the stimulation of arachidonate metabolism in those cells.

Deposition of Terminal C5b–9 Complement Complexes on Erythrocytes and Leukocytes during Cardiopulmonary Bypass

Factors influencing erythrocyte destruction in artificial organs

Blood is exposed to various dynamic forces during cardiopulmonary bypass (CPB). Understanding the damaging nature of these forces is paramount for research and development of the CPB circuit. The object of this study was to identify the most damaging dynamic non-physiological forces and then quantify this damage. A series of in vitro experiments simulated the different combinations of dynamic forces experienced during CPB while damage to the blood was closely monitored. A combination of air interface (a) and negative pressure (P) caused the greatest rate of change in plasma Hb (deltap Hb) (4.94 x 10(-3) mg/dl/s) followed by negative pressure and then an air interface. Shear stresses, positive pressures, wall impact forces and a blood-nonendothelial surface caused the least damage (0.26 x 10(-3) mg/dl/s). An air interface showed no threshold value for blood damage, with the relationship between the size of the interface and the blood damage modelled by a second-order polynomial. However, negative pressure did exhibit a threshold value at -120 mm Hg, beyond which point there was a linear relationship. Investigating the reasons for the increased blood trauma caused by the low-pressure suction (LPS) system makes it clear how research into minimizing or completely avoiding certain forces must be the next step to advancing extracorporeal technology.

Investigation and quantification of the blood trauma caused by the combined dynamic forces experienced during cardiopulmonary bypass.

Typical extracorporeal circulation systems subject blood to abnormal and severe physical conditions. The local rate of mechanical hemolysis under such conditions is postulated to be a function of the local rate of mechanical energy dissipation. This hypothesis was tested by examining the rates of hemolysis in four types of flow. The average rate of hemolysis is expressed as a power function of the average dissipation rate. In the absence of cavitation, the lysis rate in all four cases depends on the average dissipation rate raised to the 1·2 power. The constant of proportionality in each case, however, depends on the spatial distribution of dissipation. The more non-uniform the dissipation, the greater the hemolysis rate for the same average dissipation rate. No statistical correlation was found between the tendency of a particular blood to lyse osmotically and the tendency to lyse mechanically.

L F Mockros

Papers

Hydrodynamic hemolysis in extracorporeal machines.