Insulin alters cytokine content in two pivotal organs after brain death: a porcine model.
BACKGROUND
To optimize the quantity and quality of organs available for transplantation, it is crucial to gain further insight into the treatment of brain dead organ donors. In the current study we hypothesized that insulin treatment after brain death alters cytokine content in the heart, liver, and kidney.


METHODS
Sixteen brain dead pigs (35-40 kg) were treated with either (1) no insulin [brain dead without insulin treatment treatment (BD)], or (2) insulin infusion intravenously (i.v.) at a constant rate of 0.6 mU/kg/min during 360 min [brain dead with insulin treatment (BD+I)]. Blood glucose was clamped at 4.5 mmol/l by infusion of 20% glucose. Blood samples for insulin, glucose, catecholamines, free fatty acids, and glucagon were obtained during the experimental period. Six hours after brain death biopsies were taken from the heart, liver, and kidney. These were analyzed for cytokine mRNA and proteins [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-6, and IL-10].


RESULTS
The BD+I compared with the BD animals had lower IL-6 concentrations in the right ventricle of the heart (P=0.001), in the renal cortex (P=0.04) and in the renal medulla (P=0.05), and lower IL-6 mRNA in the renal medulla (P=0.0002). Furthermore, the BD+I animals had lower concentrations in the renal medulla of IL-10 (P=0.01), and tended to have lower TNF-alpha in the renal cortex (P=0.06) than the BD animals. In the right ventricle of the heart TNF-alpha mRNA and IL-10 mRNA were higher in the BD+I than in the BD group (P=0.002 and 0.004).


CONCLUSIONS
Insulin has anti-inflammatory effects on cytokine concentration in the heart and kidney after brain death.
Barklin
A
A
Department of Anaesthesiology and Intensive Care, Aarhus University Hospital, Aarhus, Denmark. Barklin@ki.au.dk
Larsson
A
A
Vestergaard
C
C
Kjaergaard
A
A
Wogensen
L
L
Schmitz
O
O
Tønnesen
E
E
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001926:Brain Death / Q000378:metabolism* / Q000473:pathology; D002395:Catecholamines / Q000097:blood; D002985:Clinical Protocols; D016207:Cytokines / Q000378:metabolism*; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005934:Glucagon / Q000097:blood; D007328:Insulin / Q000502:physiology*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine
D001786:Blood Glucose; D002395:Catecholamines; D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D005934:Glucagon