Kidney Week

Abstract: PO0379

Pretreatment with Low-Dose Lipopolysaccharide Attenuates Ischemia Reperfusion-Induced Vascular Congestion Through Vasoconstriction of the Outer Medulla During Reperfusion

Session Information

• AKI: Mechanisms of Injury
  November 04, 2021 | Location: On-Demand, Virtual Only
  Abstract Time: 10:00 AM - 12:00 PM

Category: Acute Kidney Injury

• 103 AKI: Mechanisms

Authors

• Ray, Sarah C., Augusta University, Augusta, Georgia, United States

Sarah C. Ray

• O'Connor, Paul, Augusta University, Augusta, Georgia, United States

Paul O'Connor,

Background

Vascular congestion in the renal outer medulla (OM) is common in acute tubular necrosis caused by ischemia and has been shown to promote tubular injury. Evidence from our laboratory suggests that vascular congestion originates in the renal venous vessels during ischemia and backfills the outer-medullary circulation with red blood cells (RBCs) during the reperfusion phase. We have previously reported that pretreatment with low dose lipopolysaccharide (LPS) attenuates ischemia reperfusion (IR) induced vascular congestion, however the mechanisms mediating this effect remain unknown. In the current study, we hypothesized that pretreatment with LPS prevents vascular congestion by limiting early reperfusion of the OM capillaries following ischemia.

Methods

To test this hypothesis, male WKY rats (12wks) were pretreated (i.p) with 1mg/kg LPS (n=6) or saline control (n=7) daily for 3 days. Rats were then anesthetized, and Transonic Laser Doppler probes were inserted in the cortex and OM. Regional kidney blood flow was then measured over 10 minutes of baseline, 45 minutes of renal artery clamping and 30 minutes of reperfusion.

Results

There were no differences in baseline blood flow between rats pretreated with low dose LPS or control (p_treat=0.51). The return of blood flow to the cortex was gradual (p_time<0.0001), reaching a plateau following 10 minutes of reperfusion in both groups (p_treat=0.98). The return of blood flow to the OM, however, rapidly returned to baseline levels within 1 minute of reperfusion only in control animals (1 min: 0 to 0.43AU). In contrast, OM blood flow returned slowly in LPS treated rats (1 min: 0 to -0.08AU) and did not return to baseline levels during the 30-minute reperfusion period (p_interaction=0.01).

Conclusion

Our data indicate that LPS pre-treatment, paradoxically, slows the early reperfusion of the renal OM through regional vasoconstriction. We speculate this effect attenuates medullary congestion by allowing RBCs in the shared venous circulation to clear. These findings support the hypothesis that backfilling of the renal medullary circulation before cortical reperfusion is restored, is responsible for the development of vascular congestion. New therapeutics focused on renal hemodynamics after ischemia may prevent much of the injury associated with acute kidney injury.

Funding

• NIDDK Support