Vasoreactivity to Acetylcholine During Porcine Kidney Perfusion for the Assessment of Ischemic Injury.

Abstract

BACKGROUND\nThe effects of renal allograft ischemic injury on vascular endothelial function have not been clearly established. The aim of this study was to examine vascular reactivity to acetylcholine (ACh) in kidneys subjected to ischemic injury and reperfusion.\n\n\nMETHODS\nPorcine kidneys were exposed to different combinations of warm ischemic time (WIT) and cold ischemic time (CIT) as follows: 15\xa0min (n\xa0=\xa07), 60\xa0min (n\xa0=\xa06), 90\xa0min (n\xa0=\xa06), or 120\xa0min (n\xa0=\xa04) WIT\xa0+\xa02 h CIT or 15\xa0min WIT\xa0+\xa016 h CIT (n\xa0=\xa08). Kidneys were reperfused at 38°C for 3 h. After reperfusion, ACh was infused into the circuit to assess endothelium-dependent vascular reactivity.\n\n\nRESULTS\nThe dose-response relationships between renal blood flow and ACh demonstrated that ACh doses of 10-10 to 10-7 mmol/L caused vasodilatation, whereas doses in the range 10-6 to 10-4 mmol/L led to vasoconstriction. For kidneys exposed to\xa015-90 min WIT, there was a clear relationship between increasing ischemic injury and reduced vasodilatation to ACh. In contrast, kidneys subjected to 120\xa0min WIT completely lost vasoreactivity. The vasodilatory response to ACh was diminished, but not lost, when CIT was increased from 2 h to 16 h. Peak renal blood flow after ACh infusion correlated with the functional parameters in kidneys with 2 h CIT (P\xa0<\xa00.05).\n\n\nCONCLUSIONS\nThe loss of renal vascular reactivity after 120\xa0min WIT suggests endothelial dysfunction leading to loss of nitric oxide synthesis/release. Measurement of vasoreactivity to ACh in an isolated organ perfusion system has the potential to be developed as a marker of ischemic renal injury before transplantation.