Normothermic perfusion of ischaemic porcine kidneys: an evaluation of ex vivo function and endothelin receptor antagonism.
BACKGROUND
Non-heart-beating donors suffer a period of warm ischaemia (WI) injury, resulting in higher rates of delayed graft function compared with heart-beating donors. Endothelin is believed to play a pathophysiological role in the intense vasospasm associated with WI. This study aimed to investigate renal function using normothermic perfusion and potential therapeutic intervention with endothelin receptor antagonism.


METHODS
Porcine kidneys, subjected to varying periods of in situ WI (<10, 30 and 60 minutes), underwent normothermic machine perfusion with a perfluorodecalin perfusate. Intrarenal vascular resistance (IRR) was measured throughout perfusion, and urine and perfusate biochemical analysis was performed after 1 and 3 hours. Endothelin receptor antagonism was tested by administration of BQ-123 and BQ-788.


RESULTS
Initial IRR during perfusion increased with WI. IRR reduced to similar levels in all WI groups after 90 minutes of perfusion, but subsequently rose after 150 minutes. BQ-123 considerably increased the initial IRR; however, it abolished the rise seen towards the end of perfusion. BQ-788 had little effect. Renal metabolism and function deteriorated with increasing WI. Perfusion had adverse effects on renal function and metabolism. Endothelin receptor antagonism had little effect on renal function.


CONCLUSIONS
This study suggests that ex vivo assessment after normothermic perfusion correlates with warm ischaemic damage. However, endothelin receptor antagonism does not ameliorate the rise in IRR or renal function after kidneys are subjected to a warm ischaemic insult.
Mann
Christopher D
CD
Department of Transplant Surgery, University Hospital of Leicester, Leicester, UK. chris.mann@doctors.org.uk
Metcalfe
Matthew S
MS
Nicholson
Michael L
ML
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D007668:Kidney / Q000098:blood supply* / Q000187:drug effects / Q000502:physiology*; D023421:Models, Animal; D009842:Oligopeptides / Q000494:pharmacology; D010101:Oxygen Consumption / Q000502:physiology; D010456:Peptides, Cyclic / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D017466:Receptors, Endothelin / Q000187:drug effects; D012039:Regional Blood Flow / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013552:Swine; D013696:Temperature; D014655:Vascular Resistance / Q000502:physiology
D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides; D010456:Peptides, Cyclic; D010880:Piperidines; D017466:Receptors, Endothelin; C086539:BQ 788; C072247:cyclo(Trp-Asp-Pro-Val-Leu)