{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:05:58Z","timestamp":1792789558115,"version":"4.5.0"},"reference-count":41,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004488","name":"Croatian Science Foundation","doi-asserted-by":"publisher","award":["HRZZ-IPS-2023-02-9650"],"award-info":[{"award-number":["HRZZ-IPS-2023-02-9650"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HRZZ-IPS-2023-02-9650"],"award-info":[{"award-number":["HRZZ-IPS-2023-02-9650"]}],"id":[{"id":"https:\/\/ror.org\/03n51vw80","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Slovenian Research and Innovation Agency","doi-asserted-by":"publisher","award":["HRZZ-IPS-2023-02-9650"],"award-info":[{"award-number":["HRZZ-IPS-2023-02-9650"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]},{"award":["HRZZ-IPS-2023-02-9650"],"award-info":[{"award-number":["HRZZ-IPS-2023-02-9650"]}],"id":[{"id":"https:\/\/ror.org\/059bp8k51","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Rijeka","award":["uniri-iskusni-biomed-23-88"],"award-info":[{"award-number":["uniri-iskusni-biomed-23-88"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"crossref"}]},{"name":"University of Rijeka","award":["uniri-iz-25-224"],"award-info":[{"award-number":["uniri-iz-25-224"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"crossref"}]},{"award":["uniri-iskusni-biomed-23-88"],"award-info":[{"award-number":["uniri-iskusni-biomed-23-88"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"publisher"}]},{"award":["uniri-iz-25-224"],"award-info":[{"award-number":["uniri-iz-25-224"]}],"id":[{"id":"https:\/\/ror.org\/05r8dqr10","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Clin. Med.","JCM"],"abstract":"<jats:p>Background\/Objectives: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response that may contribute to postoperative organ dysfunction. However, the effects of pulsatile and non-pulsatile CPB on the inflammatory response remain incompletely understood. This study investigated the perioperative dynamics of interleukin (IL)-1\u03b2, IL-18, and IL-18 binding protein (IL-18BP), as pre-specified secondary inflammatory biomarker analysis of a prospective, multicentric, randomized trial (ISRCTN11243508), in patients undergoing cardiac surgery with pulsatile or non-pulsatile CPB and evaluated their relationships with routine inflammatory and myocardial injury biomarkers. Methods: In this study 142 patients undergoing elective cardiac surgery were randomized to pulsatile (Group P) or non-pulsatile (Group NP) CPB, and 129 were analyzed (pulsatile, n = 63; non-pulsatile, n = 66). Blood samples were collected before surgery and at five postoperative time points. Plasma concentrations of IL-1\u03b2, IL-18, and IL-18BP were measured by ELISA. Leukocyte count, C-reactive protein (CRP), procalcitonin (PCT), high-sensitivity cardiac troponin I (hsTnI), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were also analyzed. The trial was powered for its primary outcome; for these secondary outcomes the achieved sample size had 80% power to detect between-group ratios of geometric means of approximately 1.27 (IL-18), 1.41 (IL-18BP) and 1.38 (IL-1\u03b2). Results: Cardiac surgery with CPB induced a marked postoperative inflammatory response in both groups: leukocyte count, CRP, PCT, IL-18, IL-18BP, hsTnI and NT-proBNP increased significantly after surgery, whereas IL-1\u03b2 remained essentially unchanged. In the pre-specified confirmatory comparison of postoperative peak concentrations, no biomarker differed significantly between groups. The 95% confidence intervals of this comparison exclude a pulsatile-flow effect on peak IL-18 larger than a 15% reduction or 19% increase, and on peak IL-18BP larger than a 26% reduction or 20% increase. A supporting mixed model for repeated measures showed no differential trajectory over time for any biomarker; its confidence intervals for the average postoperative effect were narrower (approximately \u00b110% for IL-18 and \u22129% to +15% for IL-18BP). The only exception was the leukocyte count, which was approximately 10% higher throughout the postoperative period in Group NP, without a differential trajectory shape. Conclusions: This pre-specified secondary analysis of a randomized trial found no evidence that pulsatile CPB reduces the early postoperative inflammatory or myocardial-injury response compared with non-pulsatile CPB for any of the eight biomarkers studied, apart from a modest difference in leukocyte count that did not survive correction for multiple comparisons. The confidence intervals obtained exclude only moderate-to-large between-group differences in IL-18 and IL-18BP; smaller true differences remain compatible with the data and cannot be ruled out at this sample size. These findings should not be interpreted as evidence of biochemical equivalence between pulsatile and non-pulsatile CPB, but they do not support a clinically important early anti-inflammatory advantage of pulsatile perfusion in this population.<\/jats:p>","DOI":"10.3390\/jcm15187228","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T11:41:35Z","timestamp":1789645295000},"page":"7228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Effects of Pulsatile and Non-Pulsatile Cardiopulmonary Bypass on Early Inflammatory Response After Cardiac Surgery: A Secondary Biomarker Analysis of a Multicentric Randomized Controlled Trial"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1944-7163","authenticated-orcid":false,"given":"Aleksandra","family":"Ljuba\u010dev","sequence":"first","affiliation":[{"name":"Department of Surgery, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Antonijo","family":"Gr\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2837-4157","authenticated-orcid":false,"given":"Lara","family":"Bati\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, University of Rijeka, Bra\u0107e Branchetta 20, 51000 Rijeka, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Matej","family":"Jenko","sequence":"additional","affiliation":[{"name":"Clinical Department of Anesthesiology and Surgical Intensive 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