alexa Normalization of nitric oxide flux improves physiological parameters of porcine kidneys maintained on pulsatile perfusion.


Journal of Transplantation Technologies & Research

Author(s): Gage FA, Vodovotz Y

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Abstract Early endothelial damage and resultant reduction in the beneficial production of nitric oxide (NO) derived from the endothelial NO synthase (eNOS) are phenomena associated with the functional degradation of transplanted kidneys. In contrast, the inflammation characteristic of kidney preservation leads to the later, detrimental expression of the inducible NO synthase (iNOS). We reasoned that provision of low-level NO (to compensate for lack of eNOS) using the chemical NO donor S-nitrosoglutathione (GSNO), along with an iNOS inhibitor (N-omega iminoethyl-L-lysine; L-NIL), might "normalize" NO levels and therefore be beneficial in maintenance of flow. Non-heartbeating donor porcine kidneys were subjected to 30-45 min warm ischemic time and stored from 3 to 30 h, simulating the time required for national sharing. The kidneys were then machine preserved with Belzer MPS (BMP) at a set systolic pressure of 40 mmHg. Eight kidneys were perfused for 5h with BMP only (Group 1 control), 8 kidneys with BMP+GSNO only (Group 2), and 8 kidneys with BMP+GSNO+L-NIL (Group 3). Lower vascular resistance (VR) is a predictor of improved end-organ function. Both Group 2 and 3 kidneys demonstrated statistically significant reduction in VR as compared to Group 1 kidneys, with Group 3 kidneys demonstrating a greater drop in VR than Group 2. Reduced oxygen saturation suggests a higher metabolic rate. Only Group 3 had lower oxygen saturation as compared to Group 1. Increased Ca2+ concentration in the perfusate is a predictor of worse end-organ function. Group 2, but not Group 3, had a higher perfusate Ca2+ concentration than Group 1. The combination of suppression of harmful amounts of NO, while supplying a constant low-level amount of NO, may improve pulsatile kidney preservation.
This article was published in Nitric Oxide and referenced in Journal of Transplantation Technologies & Research

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