Cytochrome P450-endogenous substrates metabolism is reduced in patients with a multiple organ dysfunction after coronary artery bypass grafting

Abstract

Abstract Aim: To evaluate endogenous toxic substrates and liver monooxygenase function in cardiosurgical patients with multiple organ dysfunction syndrome (MODS). Methods: 45 patients with MODS and 34 patients with an uneventful postoperative period were studied. The endogenous substrates were quantified with blood middle molecules (MM). Liver monooxygenase function was evaluated with antipyrine (AP) pharmacokinetics. Results: On the first postoperative day, MODS patients were characterized by high concentration of toxic substrates (MM: +43.8%) and a significant decrease in liver monooxygenase function (AP clearance: −44%), while controls patients had a mild increase in endogenous substrates and a slight depression in monooxygenase function. On the 3rd–4th postoperative day, in the main group, endogenous substrates increased (MM: +53.1%), while in the control group toxic substrates decreased (MM: +6.9%). In both groups, an increase in liver monooxygenase function was noticed. Major differences were observed on the 10th–12th postoperative day. In the main group, toxic substrates remained elevated (MM: +37.5%) and monooxygenase function was depressed (AP clearance: −45.4%), while in the control group endogenous substrates and monooxygenase function were equal to the baseline. The correlation analysis showed a negative relationship between AP pharmacokinetics and endogenous substrates. Conclusion: Slowdown in liver microsomal oxidation is one of the main reasons for the accumulation of endogenous toxic substrates in MODS cardiac patients.