title: Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia.
abstract: Insufficient cardiac preload and impaired contractility are frequent in early sepsis. We explored the effects of acute cardiac preload reduction and dobutamine on hepatic arterial (Qha) and portal venous (Qpv) blood flows during endotoxin infusion. We hypothesized that the hepatic arterial buffer response (HABR) is absent during preload reduction and reduced by dobutamine. In anesthetized pigs, endotoxin or vehicle (n = 12, each) was randomly infused for 18 h. HABR was tested sequentially by constricting superior mesenteric artery (SMA) or inferior vena cava (IVC). Afterward, dobutamine at 2.5, 5.0, and 10.0 μg/kg per minute or another vehicle (n = 6, each) was randomly administered in endotoxemic and control animals, and SMA was constricted during each dose. Systemic (cardiac output, thermodilution) and carotid, splanchnic, and renal blood flows (ultrasound Doppler) and blood pressures were measured before and during administration of each dobutamine dose. HABR was expressed as hepatic arterial pressure/flow ratio. Compared with controls, 18 h of endotoxin infusion was associated with decreased mean arterial blood pressure [49 ± 11 mmHg vs. 58 ± 8 mmHg (mean ± SD); P = 0.034], decreased renal blood flow, metabolic acidosis, and impaired HABR during SMA constriction [0.32 (0.18-1.32) mmHg/ml vs. 0.22 (0.08-0.60) mmHg/ml; P = 0.043]. IVC constriction resulted in decreased Qpv in both groups; whereas Qha remained unchanged in controls, it decreased after 18 h of endotoxemia (P = 0.031; constriction-time-group interaction). One control and four endotoxemic animals died during the subsequent 6 h. The maximal increase of cardiac output during dobutamine infusion was 47% (22-134%) in controls vs. 53% (37-85%) in endotoxemic animals. The maximal Qpv increase was significant only in controls [24% (12-47%) of baseline (P = 0.043) vs. 17% (-7-32%) in endotoxemia (P = 0.109)]. Dobutamine influenced neither Qha nor HABR. Our data suggest that acute cardiac preload reduction is associated with preferential hepatic arterial perfusion initially but not after established endotoxemia. Dobutamine had no effect on the HABR.
authors.affiliation: Dept. of Intensive Care Medicine, Bern Univ. Hospital, Inselspital, CH-3010 Bern, Switzerland. stephan.jakob@insel.ch
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Jakob
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
authors.forename: Francesca
authors.initials: F
authors.lastname: Porta
authors.forename: Bruno M
authors.initials: BM
authors.lastname: Balsiger
authors.forename: Lukas
authors.initials: L
authors.lastname: Brander
authors.forename: Rafael
authors.initials: R
authors.lastname: Knuesel
authors.forename: Hong-Qiang
authors.initials: HQ
authors.lastname: Feng
authors.forename: Anna
authors.initials: A
authors.lastname: Kolarova
authors.forename: Yingmin
authors.initials: Y
authors.lastname: Ma
authors.forename: Jukka
authors.initials: J
authors.lastname: Takala
mesh_terms: D000138:Acidosis / Q000188:drug therapy / Q000503:physiopathology; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D002302:Cardiac Output / Q000187:drug effects / Q000502:physiology; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002339:Carotid Arteries / Q000187:drug effects / Q000503:physiopathology; D004280:Dobutamine / Q000494:pharmacology*; D019446:Endotoxemia / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004731:Endotoxins / Q000633:toxicity; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006499:Hepatic Artery / Q000187:drug effects / Q000503:physiopathology; D008102:Liver Circulation / Q000187:drug effects* / Q000502:physiology; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D013152:Splanchnic Circulation / Q000187:drug effects / Q000502:physiology; D013552:Swine; D018608:Ultrasonography, Doppler
chemical_list: D002316:Cardiotonic Agents; D004731:Endotoxins; D009566:Nitrates; D009573:Nitrites; D000804:Angiotensin II; D004280:Dobutamine