Effects of cardiopulmonary bypass on kidney and brain tissue microcirculatory perfusion and oxygenation

Purpose: Acute kidney and brain injury are unresolved clinical complications following cardiac surgery requiring (CPB). Using a sheep model of CPB in which renal and cerebral tissue microcirculatory perfusion, oxygenation are continuously monitored before, during and 48-hours post CPB renal medullary and cerebral tissue hypoxia were studied as mechanistic processes.

Methods: Seven adult merino sheep underwent aseptic surgery prior to CPB to implant a transit-time flow probe around the left renal artery and fibre-optic probes in the renal medulla and the frontal cortex of the brain. Following general anaesthesia and a thoracotomy, CPB was commenced for 2 hours at a non-pulsatile pump flow of 2.4 L/min/m2, a mean arterial pressure of 70 mmHg and a body temperature of 36°C (normal ovine basal temperature 39°C), after which animals were weaned from CPB and allowed to emerge from anaesthesia. Renal blood flow (RBF), renal medullary and cerebral tissue oxygenation were continuously measured before, during and for 48 hours following CPB. Plasma levels of neurofilament light chain (NfL) were measured as a functional biomarker of axonal brain injury.

Results: Commencement of CPB was associated with significant reductions in RBF (220 ± 16 to 107 ± 12 mL/min; p < 0.001), and renal medullary tissue oxygenation (33 ± 5 to 14 ± 6 mmHg; p = 0.049), compared with the non-anaesthetised state (pre-CPB). Commencement of CPB was not associated with reduced cerebral tissue oxygenation (25 ± 3 to 47 ± 15 mmHg, p=0.70). In the postoperative period, despite RBF returning towards pre-CPB levels at 4 hours following the surgical procedure, renal medullary tissue oxygenation remained significantly lower for up to 12 hours relative to the pre-CPB timepoint (33 ± 5 to 15 ± 4 mmHg, p = 0.014). There were no significant reductions in cerebral tissue oxygenation during the 48-hour postoperative period. Plasma NfL was significantly elevated from 444 ± 73 (pre-CPB) to 909 ± 126 pg /ml (p = 0.006) at 48 hours of the postoperative period.

Conclusion: Intra- and postoperative renal medullary tissue hypoxia may play a critical role in the development of postoperative acute kidney injury following cardiac surgery with CPB. In contrast, this procedure does not induce hypoxia in the frontal cerebral cortex, but it results in significantly increased plasma levels of the clinical brain injury biomarker, NfL

Identify the source of the funding for this research project: National Health & Medical Research Council of Australia. Medical Research Future Fund, Australia.