Cardiotrophin-1 reduces ischemia/reperfusion injury during liver transplant.

BACKGROUND: Orthotopic liver transplantation (OLT) is currently the elective treatment for advanced liver cirrhosis and acute liver failure. Ischemia/reperfusion damage may jeopardize graft function during the postoperative period. Cardiotrophin-1 (CT-1) has demonstrated cytoprotective properties in different experimental models of liver injury. There is no evidence to demonstrate its potential use in the prevention of the ischemia/reperfusion injury that occurs during OLT. The present study is the first report to show that the administration of CT-1 to donors would benefit the outcome of OLT. MATERIALS AND METHODS: We tested the cytoprotective effect of CT-1 administered to the donor prior to OLT in an experimental pig model. Hemodynamic changes, hepatic histology, cell death parameters, activation of cell signaling pathways, oxidative and nitrosative stress, and animal survival were analyzed. RESULTS: Our data showed that CT-1 administration to donors increased animal survival, improved cardiac and respiratory functions, and reduced hepatocellular injury as well as oxidative and nitrosative stress. These beneficial effects, related to the activation of AKT, ERK, and STAT3, reduced caspase-3 activity and diminished IL-1ß and TNF-α expression together with IL-6 upregulation in liver tissue. CONCLUSIONS: The administration of CT-1 to donors reduced ischemia/reperfusion injury and improved survival in an experimental pig model of OLT.

Comparison of the cardiopulmonary parameters after induction of anaesthesia with alphaxalone or etomidate in dogs.

OBJECTIVE: To compare the cardiorespiratory effects and quality of induction of and recovery from anaesthesia following etomidate or alphaxalone-HPCD IV. STUDY DESIGN: Randomized 'blinded' cross-over study. Twenty-four hours was allowed between phases. ANIMALS: Eight healthy adult Beagles (four male, four female). METHODS: Dogs were anaesthetized with sevoflurane for instrumentation, then allowed to awake. They then received etomidate (treatment E) or alphaxalone-HPCD (treatment A) intravenously to effect. Heart rate (HR), body temperature, invasive arterial pressures (AP), systemic vascular resistance index (SVRI), stroke volume index, cardiac index (CI), contractility, respiratory rate, central venous pressure, and capnometry were obtained before anaesthetic induction (baseline), 30 seconds and 1 minute after induction, after intubation, one minute after intubation, and for every 5 minutes afterwards until the dog began to swallow and the trachea was extubated. Arterial bloods were taken for analyses before induction, after intubation and every 10 minutes thereafter. The dogs breathed room air. The quality of induction of and recovery from anaesthesia were scored categorically. Statistical analyses used anova for repeated measures, paired t-tests or Wilcoxon signed rank-test as relevant. Significance was set at p < 0.05. RESULTS: The induction doses required were (mean ± SD) 2.91 ± 0.41 mg kg(-1) and 4.15 ± 0.7 mg kg(-1) for treatment E and A respectively. No significant changes in cardiovascular parameters were observed with treatment E. Treatment A resulted in statistically significant increases in HR and CI and reductions of APs and SVRI. Time to extubation was longer with treatment A (25 ± 7 minutes) than with treatment E (17 ± 4 minutes). Dogs became hypoxic with both treatments. The quality of induction and recovery were excellent with treatment A, but significantly less satisfactory with treatment E (recovery score, treatment E median 1, range 0-2; treatment A median 0, range 0-1). CONCLUSIONS AND CLINICAL RELEVANCE: Alphaxalone-HPCD caused significant tachycardia and increase in CI, and statistically (but not clinically) significant decreases in APs and SVRI. Etomidate caused no statistically significant cardiovascular changes. Quality of recovery was better with alfaxalone-HPCD. Both agents caused short-lived hypoxia, and oxygen supplementation is advisable.