Reversal of renal tissue hypoxia during experimental cardiopulmonary bypass in sheep by increased pump flow and arterial pressure

Abstract

Aim Renal tissue hypoxia during cardiopulmonary bypass could contribute to the pathophysiology of acute kidney injury. We tested whether renal tissue hypoxia can be alleviated during cardiopulmonary bypass by the combined increase in target pump flow and mean arterial pressure. Methods Cardiopulmonary bypass was established in eight instrumented sheep under isoflurane anaesthesia, at a target continuous pump flow of 80 mL·kg−1 min−1 and mean arterial pressure of 65 mmHg. We then tested the effects of simultaneously increasing target pump flow to 104 mL·kg−1 min−1 and mean arterial pressure to 80 mmHg with metaraminol (total dose 0.25‐3.75 mg). We also tested the effects of transitioning from continuous flow to partially pulsatile flow (pulse pressure ~15 mmHg). Results Compared with conscious sheep, at the lower target pump flow and mean arterial pressure, cardiopulmonary bypass was accompanied by reduced renal blood flow (6.8 ± 1.2 to 1.95 ± 0.76 mL·min−1 kg−1) and renal oxygen delivery (0.91 ± 0.18 to 0.24 ± 0.11 mL·O2 min−1 kg−1). There were profound reductions in cortical oxygen tension (PO2) (33 ± 13 to 6 ± 6 mmHg) and medullary PO2 (31 ± 12 to 8 ± 8 mmHg). Increasing target pump flow and mean arterial pressure increased renal blood flow (to 2.6 ± 1.0 mL·min−1 kg−1) and renal oxygen delivery (to 0.32 ± 0.13 mL·O2 min−1kg−1) and returned cortical PO2 to 58 ± 60 mmHg and medullary PO2 to 28 ± 16 mmHg; levels similar to those of conscious sheep. Partially pulsatile pump flow had no significant effects on renal perfusion or oxygenation. Conclusions Renal hypoxia during experimental CPB can be corrected by increasing target pump flow and mean arterial pressure within a clinically feasible range.

Influence of moderate hypothermia on renal and cerebral haemodynamics and oxygenation during experimental cardiopulmonary bypass in sheep

“…In contrast to the renal medulla, we did not observe hypoxia in the renal cortex during the standard procedure. This finding is consistent with those from some of our previous CPB studies in sheep 7,10 but not with the others 8,9 in which we observed cortical tissue hypoxia during the standard procedure. The variability in our findings with regard to the renal cortex likely reflects some degree of susceptibility to hypoxia during CPB.…”

“…In contrast to the situation in the brain, there was marked hypoxia in the renal medulla during the standard procedure, confirming our previous findings 7–10 . Our observations provide further support for the proposition that standard perfusion conditions used in current clinical practice are inadequate for prevention of renal medullary hypoxia 1 .…”

“…We have recently used an ovine model of CPB performed under mild hypothermia (the standard procedure in the current study) to investigate the potential to alter perfusion conditions to improve renal medullary oxygenation. We have shown that increasing pump flow and target MAP restored renal medullary PO 2 to the level in conscious sheep 7,9 . However, blood transfusion 10 or use of pulsatile flow 9 did not improve renal medullary oxygenation.…”

Intra‐operative and early post‐operative prediction of cardiac surgery‐associated acute kidney injury: Urinary oxygen tension compared with plasma and urinary biomarkers

“…It appears that whole kidney oxygenation in general, and renal medullary tissue oxygenation specifically, can be improved during CPB by increasing pump flow and/or arterial pressure. 8,14,34 Indeed, in a recent clinical trial of goal directed perfusion, in which the primary intervention was increased pump flow during CPB, the incidence of post-operative AKI was reduced from 24.7% to 15.4%. 35 Thus, there is potential for management of perfusion conditions to be guided by continuous measurement of urinary…”

Emerging benefits and drawbacks of α2‐adrenoceptor agonists in the management of sepsis and critical illness

“…Therefore, it is conceivable that that intra‐operative neuroinflammation (i.e., activated microglia) may be a contributing factor for post‐operative cognitive dysfunction (Safavynia & Goldstein, 2019). There is also extensive experimental evidence that intraoperative overstimulation of renal SNA during CPB leads to tissue hypoperfusion and hypoxia, particularly within the renal medulla (Evans et al, 2020; Iguchi et al, 2019, 2020; Lankadeva et al, 2019; Lankadeva et al, 2020, 2021). Thus, renal medullary hypoxia, as indirectly assessed by the progressive development of a greater degree of bladder urinary hypoxia during CPB, has been reported in the subgroup of patients that developed post‐operative AKI (Zhu et al, 2018).…”