title: Impaired microcirculatory perfusion in a rat model of cardiopulmonary bypass: the role of hemodilution.
abstract: Although hemodilution is attributed as the main cause of microcirculatory impairment during cardiopulmonary bypass (CPB), this relationship has never been investigated. We investigated the distinct effects of hemodilution with or without CPB on microvascular perfusion and subsequent renal tissue injury in a rat model. Male Wistar rats (375-425 g) were anesthetized, prepared for cremaster muscle intravital microscopy, and subjected to CPB (n = 9), hemodilution alone (n = 9), or a sham procedure (n = 6). Microcirculatory recordings were performed at multiple time points and analyzed for perfusion characteristics. Kidney and lung tissue were investigated for mRNA expression for genes regulating inflammation and endothelial adhesion molecule expression. Renal injury was assessed with immunohistochemistry. Hematocrit levels dropped to 0.24 ± 0.03 l/l and 0.22 ± 0.02 l/l after onset of hemodilution with or without CPB. Microcirculatory perfusion remained unaltered in sham rats. Hemodilution alone induced a 13% decrease in perfused capillaries, after which recovery was observed. Onset of CPB reduced the perfused capillaries by 40% (9.2 ± 0.9 to 5.5 ± 1.5 perfused capillaries per microscope field; P < 0.001), and this reduction persisted throughout the experiment. Endothelial and inflammatory activation and renal histological injury were increased after CPB compared with hemodilution or sham procedure. Hemodilution leads to minor and transient disturbances in microcirculatory perfusion, which cannot fully explain impaired microcirculation following cardiopulmonary bypass. CPB led to increased renal injury and endothelial adhesion molecule expression in the kidney and lung compared with hemodilution. Our findings suggest that microcirculatory impairment during CPB may play a role in the development of kidney injury.
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Integrated Neurovascular Biology, INSERM U1083, CNRS UMR 6214, LUNAM University, Université d'Angers, Angers, France n.koning@vumc.nl.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Koning
authors.affiliation: Department of Cardiothoracic Anesthesiology, Medical Center Leeuwarden, Leeuwarden, The Netherlands; Department of Intensive Care Medicine, Medical Center Leeuwarden, Leeuwarden, The Netherlands;
authors.forename: Fellery
authors.initials: F
authors.lastname: de Lange
authors.affiliation: Department of Cardiothoracic Surgery, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Alexander B A
authors.initials: AB
authors.lastname: Vonk
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Cardiothoracic Surgery, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Yunus
authors.initials: Y
authors.lastname: Ahmed
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Charissa E
authors.initials: CE
authors.lastname: van den Brom
authors.affiliation: Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Sylvia
authors.initials: S
authors.lastname: Bogaards
authors.affiliation: Department of Critical Care, Pathology, and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands;
authors.forename: Matijs
authors.initials: M
authors.lastname: van Meurs
authors.affiliation: Department of Anesthesiology, University Medical Center Groningen, Groningen, The Netherlands; Department of Critical Care, Pathology, and Medical Biology, University Medical Center Groningen, Groningen, The Netherlands;
authors.forename: Rianne M
authors.initials: RM
authors.lastname: Jongman
authors.affiliation: Department of Internal Medicine, Laboratory for Metabolism and Vascular Medicine, Maastricht University Medical Center, Maastricht, The Netherlands;
authors.forename: Casper G
authors.initials: CG
authors.lastname: Schalkwijk
authors.affiliation: Department of Pathology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Mark P V
authors.initials: MP
authors.lastname: Begieneman
authors.affiliation: Department of Cardiothoracic Surgery, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands; Department of Pathology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Hans W
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Cardiovascular Surgery, INSERM U1083, CNRS UMR 6214, LUNAM University, Université d'Angers, Angers, France; and.
authors.forename: Christophe
authors.initials: C
authors.lastname: Baufreton
authors.affiliation: Department of Anesthesiology, Institute for Cardiovascular Research, VU University Medical Center, Amsterdam, The Netherlands;
authors.forename: Christa
authors.initials: C
authors.lastname: Boer
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D055371:Acute Lung Injury / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002196:Capillaries / Q000503:physiopathology*; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005786:Gene Expression Regulation; D006438:Hemodilution / Q000009:adverse effects*; D018836:Inflammation Mediators / Q000378:metabolism; D000069416:Intravital Microscopy; D007668:Kidney / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008297:Male; D008833:Microcirculation; D023421:Models, Animal; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D015815:Cell Adhesion Molecules; D016207:Cytokines; D018836:Inflammation Mediators
keywords: acute kidney injury; cardiopulmonary bypass; endothelium; hemodilution; microcirculation