title: Dobutamine pretreatment improves survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat.
abstract: Dobutamine is recommended for the treatment of sepsis-related circulatory failure in international guidelines. Furthermore, dobutamine has been demonstrated to improve liver function and hepatic perfusion after experimental hemorrhagic shock. Yet, it is unknown whether dobutamine may also induce hepatoprotective effects in sepsis. This study was designed to investigate the effect of dobutamine on survival, hepatic function, and microcirculation after polymicrobial sepsis in rat. Under general anesthesia, male Sprague-Dawley rats (n = 25/group) underwent pretreatment with dobutamine (10 μg/kg per minute) in the presence or absence of β1-receptor antagonist esmolol (500 μg/kg per minute), esmolol alone, or vehicle for 6 h, before induction of sepsis (cecal ligation and incision [CLI]). Sham-operated animals were treated likewise but underwent no CLI. Five hours after CLI, either liver function was assessed by plasma disappearance rate of indocyanine green (n = 5/group), or intravital microscopy was performed (n = 5/group) for evaluation of hepatic perfusion index and hepatic integrity (as propidium iodide-stained cells per field). Alternatively, survival time after induction of CLI was monitored under general anesthesia (n = 15/group). Compared with controls, dobutamine pretreatment significantly improved plasma disappearance rate of indocyanine green (13.8% ± 4.1% vs. 20.6% ± 4.6%; P = 0.029), hepatic perfusion index (275.0 ± 126.1 vs. 703.5 ± 177.4 pL/s per mm; P < 0.001), hepatocellular injury (22.2 ± 6.7 vs. 6.4 ± 3.1 cells per field; P < 0.001), and survival time (326 ± 20 vs. 603 ± 41 min; P < 0.001). Coadministration of esmolol abolished the protective effect of dobutamine completely. Our results indicate that pretreatment with dobutamine may improve survival, liver function, and hepatic microcirculation after polymicrobial sepsis in rat via β1-adrenoceptor activation. Dobutamine could therefore play a relevant role for hepatoprotection under septic conditions.
authors.affiliation: Department of Anesthesiology, Critical Care and Pain Medicine, Saarland University Medical Center, Homburg (Saar), Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Fink
authors.forename: Paul
authors.initials: P
authors.lastname: Heymann
authors.forename: Stefanie
authors.initials: S
authors.lastname: Taha-Melitz
authors.forename: Anas
authors.initials: A
authors.lastname: Taha
authors.forename: Beate
authors.initials: B
authors.lastname: Wolf
authors.forename: Hauke
authors.initials: H
authors.lastname: Rensing
authors.forename: Thomas
authors.initials: T
authors.lastname: Volk
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Mathes
mesh_terms: D000818:Animals; D004280:Dobutamine / Q000627:therapeutic use*; D006439:Hemodynamics / Q000187:drug effects; D008099:Liver / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D051381:Rats; D018805:Sepsis / Q000188:drug therapy*
chemical_list: D004280:Dobutamine