0888. Administration of tetrahydrobiopterin (BH4) protects renal microcirculation after ischemia and reperfusion

Introduction

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

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

Methods

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

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 1 Microcirculatory parameters in the 3 groups

Conclusions

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.