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Renal medullary and urinary oxygen tension during cardiopulmonary bypass in the rat.

ABSTRACT: Renal hypoxia could result from a mismatch in renal oxygen supply and demand, particularly in the renal medulla. Medullary hypoxic damage is believed to give rise to acute kidney injury, which is a prevalent complication of cardiac surgery performed on cardiopulmonary bypass (CPB). To determine the mechanisms that could lead to medullary hypoxia during CPB in the rat kidney, we developed a mathematical model which incorporates (i) autoregulation of renal blood flow and glomerular filtration rate, (ii) detailed oxygen transport and utilization in the renal medulla and (iii) oxygen transport along the ureter. Within the outer medulla, the lowest interstitial tissue P$_{\rm O2}$, which is an indicator of renal hypoxia, is predicted near the thick ascending limbs. Interstitial tissue P$_{\rm O2}$ exhibits a general decrease along the inner medullary axis, but urine P$_{\rm O2}$ increases significantly along the ureter. Thus, bladder urinary P$_{\rm O2}$ is predicted to be substantially higher than medullary P$_{\rm O2}$. The model is used to identify the phase of cardiac surgery performed on CPB that is associated with the highest risk for hypoxic kidney injury. Simulation results indicate that the outer medulla's vulnerability to hypoxic injury depends, in part, on the extent to which medullary blood flow is autoregulated. With imperfect medullary blood flow autoregulation, the model predicts that the rewarming phase of CPB, in which medullary blood flow is low but medullary oxygen consumption remains high, is the phase in which the kidney is most likely to suffer hypoxic injury.

SUBMITTER: Sgouralis I

PROVIDER: S-EPMC5432426 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ObjectiveMetabolism management plays an essential role during cardiopulmonary bypass (CPB). There are different metabolic management devices integrated to heart-lung machines; the most commonly used and accepted metabolic target is indexed oxygen delivery (DO2i) (280 mL/min/m2) and cardiac index (CI) (2.4 L/min/m2), which can be managed independently or according to other metabolic parameters. Our objective was to compare lactate production during CPB procedures using different metabolic management: DO2i in relation to indexed oxygen extraction ratio (O2ERi) and CI in relation to mixed venous oxygen saturation (SvO2).MethodsData on 500 CPB procedures were retrospectively collected in a specialized regional tertiary cardiac surgery center in Italy between September and 2012 and November 2019. In group A, the DO2i with 280 mL/min/m2 target in relation to O2ERi 25% was used; in group B, CI with 2.4 L/min/m2 target in relation to SvO2 75% was used. During CPB, serial arterial blood gas analyses with blood lactate and glucose determinations were obtained. Hyperlactatemia (HL) was defined as a peak arterial blood lactate concentration >3 mmol/L. The postoperative outcome of patients with or without HL was compared.ResultsEight pre- and intraoperative factors were found to be significantly associated with peak blood lactate level during CPB at univariate analysis. HL (>3 mmol/L) was detected in 15 (6%) patients of group A and in 42 (16.8%) patients of group B (P = .022); hyperglycemia (>160 mg/dL) was found in 23 (9.2%) patients of group A and in 53 (21.2%) patients of group B (P = .038). Patients with HL during CPB had a significant increase in serum creatinine value, higher rate of prolonged mechanical ventilation time and intensive care unit stay. A cutoff of DO2i <270 mL/min/m2 in relation to O2ERi >35% in group A and a cutoff of CI <2.4 L/min/m2 in relation to SvO2 <65% in group B were found to have a positive predictive value of 80% and 75% for HL, respectively. A cutoff of DO2i >290 mL/min/m2 in relation to O2ERi 24% in group A and a cutoff of CI >2.4 L/min/m2 in relation to SvO2 >75% in group B were found to have a negative predictive value of 78% and 62% for HL, respectively.ConclusionsThis retrospective observational analysis showed that management of DO2i in relation to O2ERi was 16% more specific in terms of negative predictive value for HL during CPB compared with the use of CI in relation to SvO2. Group A reported a significant reduction in the incidence of intraoperative lactate peak, correlated with postoperative reduction of serum creatinine value, mechanical ventilation time, and intensive care unit stay, compared with group B.

Project description:BACKGROUND:The urinary proteome of patients undergoing cardiopulmonary bypass (CPB) may provide important insights into systemic and renal changes associated with the procedure. Such information may ultimately provide a basis to differentiate changes or properties associated with the development of acute kidney injury. While mass spectrometry (MS) analysis offers the potential for in-depth compositional analysis it is often limited in coverage and relative quantitation capacity. The aim of this study was to develop a process flow for the preparation and comparison of the intraoperative urinary proteome. METHODS:Urines were collected from patients at the start of CPB and 1-h into CPB. Pooled samples (n = 5) from each time point were processed using a modified Filter Assisted Sample Preparation protocol. The resulting peptides were analyzed by 2D-LC-MS/MS and by 1D-LC-MS/MS SWATH (Sequential Window acquisition of All Theoretical fragment ion spectra). RESULTS:The 2D-LC-MS/MS analysis identified 1324 proteins in the two pools, of which 744 were quantifiable. The SWATH approach provided quantitation for 730 proteins, 552 of which overlapped with the common population from the 2D-IDA results. Intensity correlation filtering between the two methods gave 475 proteins for biological interpretation. Proteins displaying greater than threefold changes (>log2 1.59) at 1-hour CPB relative to the initiation of CPB (26 down-regulated and 22 up-regulated) were selected for further analysis. Up-regulated proteins were enriched in GO terms related to humoral immune response, predominantly innate immunity (C4b, lactotransferrin, protein S100-A8, cathelicidin, myeloperoxidase) and extracellular matrix reorganization (e.g. MMP-9). CONCLUSIONS:This study describes a scheme for processing urine from patients undergoing CPB for mass spectrometry-based analysis. The introduction of SWATH into the workflow offers a sample and instrument sparing approach to obtaining consistent in-depth sample analysis. The design of the methodology is such that it can be readily applied to large numbers of clinical samples with the potential for automation. The results also suggest that activation of the innate immune responses occur during cardiac bypass surgery.

Project description:BackgroundContinuous measurement of urinary PO2 (PuO2) is being applied to indirectly monitor renal medullary PO2. However, when applied to critically ill patients with shock, its measurement may be affected by changes in FiO2 and PaO2 and potential associated O2 diffusion between urine and ureteric or bladder tissue. We aimed to investigate PuO2 measurements in septic shock patients with a fiberoptic luminescence optode inserted into the urinary catheter lumen in relation to episodes of FiO2 change. We also evaluated medullary and urinary oxygen tension values in Merino ewes at two different FiO2 levels.ResultsIn 10 human patients, there were 32 FiO2 decreases and 31 increases in FiO2. Median pre-decrease FiO2 was 0.36 [0.30, 0.39] and median post-decrease FiO2 was 0.30 [0.23, 0.30], p = 0.006. PaO2 levels decreased from 83 mmHg [77, 94] to 72 [62, 80] mmHg, p = 0.009. However, PuO2 was 23.2 mmHg [20.5, 29.0] before and 24.2 mmHg [20.6, 26.3] after the intervention (p = 0.56). The median pre-increase FiO2 was 0.30 [0.21, 0.30] and median post-increase FiO2 was 0.35 [0.30, 0.40], p = 0.008. PaO2 levels increased from 64 mmHg [58, 72 mmHg] to 71 mmHg [70, 100], p = 0.04. However, PuO2 was 25.0 mmHg [IQR: 20.7, 26.8] before and 24.3 mmHg [IQR: 20.7, 26.3] after the intervention (p = 0.65). A mixed linear regression model showed a weak correlation between the variation in PaO2 and the variation in PuO2 values. In 9 Merino ewes, when comparing oxygen tension levels between FiO2 of 0.21 and 0.40, medullary values did not differ (25.1 ± 13.4 mmHg vs. 27.9 ± 15.4 mmHg, respectively, p = 0.6766) and this was similar to urinary oxygen values (27.1 ± 6.17 mmHg vs. 29.7 ± 4.41 mmHg, respectively, p = 0.3192).ConclusionsChanges in FiO2 and PaO2 within the context of usual care did not affect PuO2. Our findings were supported by experimental data and suggest that PuO2 can be used as biomarker of medullary oxygenation irrespective of FiO2.

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Renal medullary and urinary oxygen tension during cardiopulmonary bypass in the rat.

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