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      Pre-treatment with the angiotensin receptor 1 blocker losartan protects renal blood flow and oxygen delivery after propofol-induced hypotension in pigs

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          Abstract

          Hypotensive events are strongly correlated to the occurrence of perioperative acute kidney injury, but the underlying mechanisms for this are not completely elucidated. We hypothesised that anaesthesia-induced hypotension causes renal vasoconstriction and decreased oxygen delivery via angiotensin II-mediated renal vasoconstriction. Pigs were anaesthetised, surgically prepared and randomised to vehicle/losartan treatment (0.15 mg*kg −1). A deliberate reduction in arterial blood pressure was caused by infusion of propofol (30 mg*kg −1) for 10 min. Renal function and haemodynamics were recorded 60 min before and after hypotension. Propofol induced hypotension in all animals ( p < 0.001). Renal blood flow (RBF) and renal oxygen delivery (RDO 2) decreased significantly regardless of treatment but more so in vehicle-treated compared to losartan-treated ( p = 0.001, p = 0.02, respectively). During recovery RBF and RDO 2 improved to a greater extent in the losartan-treated compared to vehicle-treated (+ 28 ml*min −1, 95%CI 8–50 ml*min −1, p = 0.01 and + 3.1 ml*min −1, 95%CI 0.3–5.8 ml*min −1, p = 0.03, respectively). Sixty minutes after hypotension RBF and RDO 2 remained depressed in vehicle-treated, as renal vascular resistance was still increased ( p < 0.001). In losartan-treated animals RBF and RDO 2 had normalised. Pre-treatment with losartan improved recovery of renal blood flow and renal oxygen delivery after propofol-induced hypotension, suggesting pronounced angiotensin II-mediated renal vasoconstriction during blood pressure reductions caused by anaesthesia.

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          Most cited references 41

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          Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.

          Intraoperative hypotension may contribute to postoperative acute kidney injury (AKI) and myocardial injury, but what blood pressures are unsafe is unclear. The authors evaluated the association between the intraoperative mean arterial pressure (MAP) and the risk of AKI and myocardial injury.
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            A clinical score to predict acute renal failure after cardiac surgery.

            The risk of mortality associated with acute renal failure (ARF) after open-heart surgery continues to be distressingly high. Accurate prediction of ARF provides an opportunity to develop strategies for early diagnosis and treatment. The aim of this study was to develop a clinical score to predict postoperative ARF by incorporating the effect of all of its major risk factors. A total of 33,217 patients underwent open-heart surgery at the Cleveland Clinic Foundation (1993 to 2002). The primary outcome was ARF that required dialysis. The scoring model was developed in a randomly selected test set (n = 15,838) and was validated on the remaining patients. Its predictive accuracy was compared by area under the receiver operating characteristic curve. The score ranges between 0 and 17 points. The ARF frequency at each score level in the validation set fell within the 95% confidence intervals (CI) of the corresponding frequency in the test set. Four risk categories of increasing severity (scores 0 to 2, 3 to 5, 6 to 8, and 9 to 13) were formed arbitrarily. The frequency of ARF across these categories in the test set ranged between 0.5 and 22.1%. The score was also valid in predicting ARF across all risk categories. The area under the receiver operating characteristic curve for the score in the test set was 0.81 (95% CI 0.78 to 0.83) and was similar to that in the validation set (0.82; 95% CI 0.80 to 0.85; P = 0.39). In conclusion, a score is valid and accurate in predicting ARF after open-heart surgery; along with increasing its clinical utility, the score can help in planning future clinical trials of ARF.
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              Association of intraoperative hypotension with acute kidney injury after elective noncardiac surgery.

              Intraoperative hypotension (IOH) may be associated with postoperative acute kidney injury (AKI), but the duration of hypotension for triggering harm is unclear. The authors investigated the association between varying periods of IOH with mean arterial pressure (MAP) less than 55, less than 60, and less than 65 mmHg with AKI.
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                Author and article information

                Contributors
                stephanie.franzen@surgsci.uu.se
                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group UK (London )
                2045-2322
                21 October 2020
                21 October 2020
                2020
                : 10
                Affiliations
                GRID grid.412354.5, ISNI 0000 0001 2351 3333, Department of Surgical Sciences, Anaesthesiology and Intensive Care, Uppsala University, , Uppsala University Hospital, ; Entrance 78, 1st floor, 75185 Uppsala, Sweden
                Article
                74640
                10.1038/s41598-020-74640-6
                7578078
                33087778
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100004359, Vetenskapsrådet;
                Funded by: Uppsala University
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                © The Author(s) 2020

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