Postoperative Heme Oxygenase Induction and Carbon Monoxide Production as a Novel Method to Assess Hepatic Regeneration and Predict Hepatic Related Morbidity After Partial Hepatectomy

The goal of this proposal is to elucidate the role of HO-1 induction in hepatic regeneration after partial hepatectomy (PH). There is a growing body of evidence that HO-1 induction through CO production has an important role in cellular protection and regeneration. To test this concept, we will monitor endogenous CO production in patients who undergo PH and analyze the relationship between CO production and hepatic regeneration. Using this approach we will test the following two hypotheses: (1) HO-1 induction after PH is proportional to the extent of the surgical resection, and (2) failure to appropriately induce HO-1 is associated with impaired hepatic regeneration. Specific Aim 1: To monitor the extent of HO-1 induction (by measuring endogenous CO production) in relationship to the extent of hepatic resection 1.1 Monitor CO in exhaled air of patients before liver resection, at 4 hours and 24 hours after PH 1.2 Monitor carboxyhemoglobin(COHb) in the arterial blood gas of patients before liver resection at 4 hours and 24 hours after PH 1.3 Analyze the relationship between CO production and the extent of hepatic resection assessed by computed scans liver volumetric study at one and three months after PH, size and weight of the resected specimen and operative report. Specific Aim 2: To analyze the relationship between HO-1 induction and the quality of post-hepatectomy liver regeneration after PH 2.1 Analyze the relationship between CO production and the quantity and quality of hepatic regeneration assessed by computed scans liver volumetric study at one and three months after PH and liver function tests after PH. 2.2 Determine the relation between postoperative liver related morbidity in patients undergoing PH and the extent of postoperative HO-1 induction.