Effects of perioperative dexmedetomidine on renal vascular function and renovascular histopathology in ovine cardiopulmonary bypass.

BACKGROUND: Cardiopulmonary bypass (CPB) is integral to the conduct of cardiac surgery but is associated with postoperative acute kidney injury (AKI). Dexmedetomidine, an α₂-adrenoceptor agonist with anti-inflammatory and sympatholytic properties, has putative renoprotective effects. In a recent meta-analysis, dexmedetomidine during CPB reduced AKI; conversely, a large, randomised trial reported an increase in postoperative AKI. Further, we found increased renal tubular injury in sheep receiving dexmedetomidine during CPB. Here, we aimed to determine whether dexmedetomidine during CPB induces changes in renal vascular reactivity or endothelial integrity that could explain focal renal tubular injury. METHODS: Fourteen instrumented Merino ewes underwent 2 h of non-pulsatile CPB (flow 70 mL/kg/min; MAP 65-75 mmHg; cooled by 3 °C) under standardised propofol-fentanyl-sevoflurane anaesthesia. Animals were randomly allocated to dexmedetomidine (0.4-0.8 µg/kg/h, n = 7) or fluid-matched saline (n = 7) from induction of anesthesia to end-CPB. Arterial pressure, renal blood flow, cortical and medullary perfusion and PO₂ were measured in vivo (n = 7/group). Post-CPB, renal interlobar arteries were isolated for wire myography. Due to standardisation failures, in vitro analyses of dose-response curves for phenylephrine were performed in n = 6 per group, while endothelial-dependent and independent relaxation responses were performed in n = 7 per group. Endothelial histology of CPB arteries was compared with arteries from a separate cohort of healthy Merino ewes (n = 7). RESULTS: In vitro functional investigations demonstrated that interlobar arteries from dexmedetomidine-treated sheep exhibited a 2.3-fold increase in phenylephrine sensitivity (pEC₅₀ 5.82 ± 0.27 vs. 5.45 ± 0.23; p = 0.034), with unchanged maximal contraction. Endothelium-dependent and independent relaxations were similar between groups, though inhibitor studies indicated a shift towards cyclooxygenase-mediated dilation under dexmedetomidine. Histology revealed intact endothelial architecture and no damage to endothelial integrity in all groups. CONCLUSIONS: Perioperative dexmedetomidine during CPB enhanced α₁-adrenergic vasoconstrictor sensitivity in renal interlobar arteries without disrupting endothelial integrity or compromising renal blood flow or intrarenal perfusion. The enhanced vasoreactivity may contribute to focal renal ischaemia and tubular injury during CPB, which cannot be detected by in vivo measurements of global and regional kidney perfusion and oxygenation. Further investigation is warranted to elucidate the pathways through which dexmedetomidine contributes to renal tubular injury during CPB.