Influence of hepatic mitochondrial redox state on complement biosynthesis and activation during and after...

We have proposed the hazardous phenomena associated with cardiopulmonary bypass (CPB) are due to metabolic derangement by hepatic mitochondrial dysfunction during and after CPB. On the contrary, complement activation and consumption during CPB is reported to be related to the morbidity associated with cardiac surgery. To determine the significance of the hepatic mitochondrial function on the morbidity of cardiac surgery, we measured the serum levels of complements (C3 and C4), activated complements (C3a and C4a), and the arterial ketone body ratio (AKBR), which reflects the hepatic mitochondrial redox state, in 30 patients undergoing CPB. The AKBR, which was at a normal level preoperatively, dropped to a critical level after the initiation of CPB and remained at a low level during the CPB, returning to the preoperative level on the second postoperative morning in a time dependent fashion. The patients group were assigned to two groups according to their AKBR on the first postoperative morning. Group I consisted of patients whose AKBR had recovered to above 0.7 on the first postoperative morning (n = 16). Group II consisted of the rest of the patients (n = 14). The serum complement concentration had considerably decreased by the end of bypass, but recovered in a time-dependent fashion after CPB. The group I patients (C3: 71% of its preoperative value, C4: 85% of its preoperative value) recovered their complements more quickly than the group II patients (C3: 56% of its preoperative value, C4: 54% of its preoperative value). However, the serum C3a and C4a concentrations increased by the end of bypass (C3a: 806% of its preoperative value, C4a: 341% of its preoperative value). The activated complements were significantly higher in the group II patients (C3a: 124% of its preoperative value, C4a: 236% of its preoperative value) than in the group I patients (C3a: 75% of its preoperative value, C4a: 113% of its preoperative value) on the first postoperative morning. It is suggested that hepatic mitochondrial function is related to recovering the complements and to reducing the activated complements after CPB.