Introduction {#Sec1}
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Abdominal aortic aneurysm surgery with supra-renal clamping is associated with potential development of renal insufficiency.  Ischemia and reperfusion (I-R) produced during the procedure induces endothelial dysfunction with a decrease in tetrahydrobiopterin (BH4), a cofactor used in nitric oxide synthesis. 

Objectives {#Sec2}
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To assess whether BH4 administration could prevent the injury to the renal microcirculation caused by supra-renal aortic clamping with I-R.

Methods {#Sec3}
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Nineteen adult sheep were anesthetized, mechanically ventilated and invasively monitored.  Renal blood-flow was measured continuously through a left lumbotomy using a peri-vascular flow probe (Transonic, USA) and an aortic clamp was positioned above the renal arteries.  After surgical preparation and stabilization, animals were randomized into 3 groups (SHAM=5, I-R=7, I-R+BH4=7).  SHAM animals underwent surgical preparation but no aortic clamping was performed.  The I-R groups were exposed to 1 hour of aortic ischemia.  The I-R+BH4 group received 20 mg/kg of BH4 before aortic clamping.  Animals were followed for a maximum of 6 hours after reperfusion.  Renal microcirculation was evaluated at baseline, and 1, 4 and 6 hours after reperfusion using Sidestream Dark Field video-microscopy (Microvision Medical, Netherlands).  We calculated perfused small vessel density (PVD), proportion of perfused small vessels (PPV) and heterogeneity of PPV (PPV-HI).  Data were analyzed using the generalized estimating equation (GEE) and p-values less than 5% were considered statistically significant.  Results are presented as median \[IQRs\]. 

Results {#Sec4}
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The systemic hemodynamics variables were preserved in all 3 groups.  BH4 was associated with improved renal function, as evaluated by creatinine after 6 hours of reperfusion in the I-R+BH4 group (14 mg/L \[13-17\]) compared to the I-R group (16 mg/L \[16-22\]) (P=0.072).Table 1Microcirculatory parameters in the 3 groupsGroupBaseline1h4h6hP Group\*TimePVD (vessels/mm)SHAM2.6 (2.5-2.7)2.7 (2.3-2.9)2.4 (2.2-2.7)2.3 (2.3-2.5) cP\<0.05I-R3.2 (2.9-3.7)2.0 (1.5-2.8) c2.1 (1.7-2.7) c1.6 (1.3-2.3) a, cI-R+BH43.2 (2.7-3.4)3.0 (2.6-3.3) b2.5 (2.0-3.1) b, c3.1 (2.4-3.8) bPPV (%)SHAM93.7 (93.3-94.7)87.6 (84.2-90.6) c83.0 (80.3-90.2) c85.5 (82.0-90.4) cP=0.269I-R97.3 (96.0-97.9)80.1 (73.5-90.2) c82.7 (68.5-88.7) c79.8 (74.9-84.6) cI-R+BH497.8 (96.8-98.3)92.3 (89.8-93.8) b, c85.9 (80.9-91.5) c89.3 (86.0-99.4) cPPV-HI (%)SHAM11.9 (8.9-13.2)18.4 (16.5-22.8) c14.2 (11.0-15.1)14.4 (11.3-39.0)P\<0.05I-R9.6 (5.5-11.0)43.0 (22.2-84.0) a, c41.8 (28.2-97.7) a, c47.3 (11.1-76.3) cI-R+BH49.3 (7.3-12.5)24.7 (17.1-32.8) c42.8 (29.1-56.2) c25.4 (2.9-40.5) c*\[values are presented as median with P25-75\]*a: significant difference between groups I-R and SHAMb: significant difference between groups I-R and BH4+I-Rc: significant difference with the baseline. 

Conclusions {#Sec5}
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In a sheep model of renal I-R, BH4 pre-treatment can prevent microvascular injury and dysfunction.  Clinical trials are warranted to evaluate the administration of BH4 to prevent I-R-induced kidney injury.