Effects of complement activation in the isolated heart. Role of the terminal complement components.

The mechanisms of the complement-mediated myocardial injury associated with ischemia and reperfusion have not been elucidated fully. Complement activation may directly mediate injury through actions of the anaphylatoxins C3a and C5a or generation of the membrane attack complex C5b-9. A model was developed to examine the direct effects of complement activation on heart function, assess myocardial tissue damage, and determine which complement components mediate tissue injury. Isolated rabbit hearts were perfused with Krebs-Henseleit buffer by using a modified Langendorff apparatus. Human plasma was added to the perfusate as a source of complement. Rabbit tissue activates human complement. Treatment with 6% normal plasma resulted in complement activation as assessed by the generation of Bb, C3a, C5a, and SC5b-9. Functional changes in cardiac performance became apparent 7-15 minutes after plasma addition and developed fully over the next 20-30 minutes. The effects were dependent on the complement titer and in...