Breath pentane as a potential biomarker for survival in hepatic ischemia and reperfusion injury--a pilot study

Abstract

Background: Exhaled pentane, which is produced as a consequence of reactive oxygen species-mediated lipid peroxidation, is a marker of oxidative stress. Propofol is widely used as a hypnotic agent in intensive care units and the operating room. Moreover, this agent has been reported to inhibit lipid peroxidation by directly scavenging reactive oxygen species. In this study, using a porcine liver ischemia-reperfusion injury model, we have evaluated the hypothesis that high concentrations of breath pentane are related to adverse outcome and that propofol could reduce breath pentane and improve liver injury and outcome in swine in this situation.

Methodology/principal findings: Twenty male swine were assigned to two groups: propofol (n = 10) and chloral hydrate groups (n = 10). Hepatic ischemia was induced by occluding the portal inflow vessels. Ischemia lasted for 30 min, followed by reperfusion for 360 min. Exhaled and blood pentane concentrations in the chloral hydrate group markedly increased 1 min after reperfusion and then decreased to baseline. Breath and blood pentane concentrations in the propofol group increased 1 min after reperfusion but were significantly lower than in the chloral hydrate group. A negative correlation was found between breath pentane levels and survival in the chloral hydrate group. The median overall survival was 251 min after reperfusion (range 150-360 min) in the chloral hydrate group. All of the swine were alive in the propofol group.

Conclusions: Monitoring of exhaled pentane may be useful for evaluating the severity of hepatic ischemia-reperfusion injury and aid in predicting the outcome; propofol may improve the outcome in this situation.

Figure 1. Changes in breath pentane concentrations.

The values are expressed as the mean±SE. ST, stabilization period; IS, ischemia period; RE, reperfusion period. A 60-min stretch from the stabilization period was used as the baseline for the breath pentane concentration. ^† P<0.05 versus the group baseline, ^‡ P<0.05 between groups.

Figure 2. Changes in blood pentane concentrations.

The values are expressed as the mean±SE. ST, stabilization period; IS, ischemia period; RE, reperfusion period. A 60-min stretch from the stabilization period was used as the baseline for the breath pentane concentration. ^† P<0.05 versus the group baseline, ^‡ P<0.05 between groups.

Figure 3. Changes in plasma aspartate aminotransferase (AST).

The values are expressed as the mean±SE. RE, reperfusion period. A 15-min stretch from the high-flow washout period was used as a baseline for AST. ^† P<0.05 versus the group baseline, ^‡ P<0.05 between groups.

Figure 4. Changes in plasma malondialdehyde (MDA).

The values are expressed as the means±SE. RE, reperfusion period. 15 min of high-flow washout period as baseline-MDA. ^† P<0.05 versus the group baseline, ^‡ P<0.05 between groups.

Figure 5. Histopathology of the liver using light (A/B) and electron (C/D) microscopy.

A: Congestion, degeneration and necrosis in the centrilobular portion of a liver from the chloral hydrate group (HE×400). B: Inflammatory cell infiltration and the degeneration of granules in the centrilobular portion of a liver from the propofol group (HE×400). C: Accumulation of high density plaques in endonuclear chromatin, bubble degeneration of mitochondria, and the disruption of hepatic sinusoid endothelium in the chloral hydrate group (×1000). D: Complete membrane and a few changes in the nuclear membrane and nucleoli in the propofol group (×1000).

Figure 6. Kaplan-Meier survival plots for the swine in the chloral hydrate (n = 10) and propofol groups (n = 10). Log rank (Mantel-Cox) P<0.05.

Figure 7. Correlation between breath pentane levels and survival following hepatic ischemia-reperfusion in the chloral hydrate group (n = 10).

Regression lines with 95% confidence intervals. HIR, hepatic ischemia-reperfusion. Pearson correlation, −0.840. P<0.05.