The Effect of Acute Normovolaemic Haemodilution on the Inflammatory Response and Clinical Outcome in Abdominal Aortic Aneurysm Repair—Results of a Pilot Trial

AbstractObjectivesTo determine the effect of acute normovolaemic haemodilution (ANH) on the inflammatory response and clinical outcome in elective open abdominal aortic aneurysm (AAA) repair.DesignRandomised controlled clinical trial.MethodsThirty-six patients were randomised to undergo ANH or act as controls. Cell salvage was permitted in both groups. Heterologous blood was transfused according to pre-determined triggers. Outcome measures were markers of the systemic inflammatory response in serum and urine observed at multiple time points, and clinical recovery.ResultsMedian 890 (range 670–1620) ml of blood was removed at ANH in 16 patients. There were no differences in peri-operative changes in neutrophil count (P=0.13), serum C-reactive protein (P=0.38), interleukin-6 (P=0.50), total antioxidant capacity (P=0.73), urinary secretion of albumin (P=0.97) or retinol binding protein (P=0.41). There were no differences in the mortality and morbidity rates, systemic inflammatory response syndrome, ITU or hospital stay.ConclusionsANH, when used in combination with cell salvage, made no impact on systemic inflammatory response and clinical outcome when compared to cell salvage alone after AAA repair. ANH cannot be recommended for routine use in patients undergoing abdominal aortic aneurysm surgery when cell salvage is available

Long-Term Ritonavir Exposure Increases Fatty Acid and Glycerol Recycling in 3T3-L1 Adipocytes as Compensatory Mechanisms for Increased Triacylglycerol Hydrolysis

Lipodystrophy with high nonesterified fatty acid (FA) efflux is reported in humans receiving highly active antiretroviral therapy (HAART) to treat HIV infection. Ritonavir, a common component of HAART, alters adipocyte FA efflux, but the mechanism for this effect is not established. To investigate ritonavir-induced changes in FA flux and recycling through acylglycerols, we exposed differentiated murine 3T3-L1 adipocytes to ritonavir for 14 d. FA efflux, uptake, and incorporation into acylglycerols were measured. To identify a mediator of FA efflux, we measured adipocyte triacylglycerol lipase (ATGL) transcript and protein. To determine whether ritonavir-treated adipocytes increased glycerol backbone synthesis for FA reesterification, we measured labeled glycerol and pyruvate incorporation into triacylglycerol (TAG). Ritonavir-treated cells had increased FA efflux, uptake, and incorporation into TAG (all P < 0.01). Ritonavir increased FA efflux without consistently increasing glycerol release or changing TAG mass, suggesting increased partial TAG hydrolysis. Ritonavir-treated adipocytes expressed significantly more ATGL mRNA (P < 0.05) and protein (P < 0.05). Ritonavir increased glycerol (P < 0.01) but not pyruvate (P = 0.41), utilization for TAG backbone synthesis. Consistent with this substrate utilization, glycerol kinase transcript (required for glycerol incorporation into TAG backbone) was up-regulated (P < 0.01), whereas phosphoenolpyruvate carboxykinase transcript (required for pyruvate utilization) was down-regulated (P < 0.001). In 3T3-L1 adipocytes, long-term ritonavir exposure perturbs FA metabolism by increasing ATGL-mediated partial TAG hydrolysis, thus increasing FA efflux, and leads to compensatory increases in FA reesterification with glycerol and acylglycerols. These changes in FA metabolism may, in part, explain the increased FA efflux observed in ritonavir-associated lipodystrophy