Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia

Author:

Jakob Stephan M.1,Bracht Hendrik1,Porta Francesca1,Balsiger Bruno M.2,Brander Lukas1,Knuesel Rafael1,Feng Hong-Qiang1,Kolarova Anna1,Ma Yingmin1,Takala Jukka1

Affiliation:

1. Departments of Intensive Care Medicine and

2. Gastroenterology, Bern University Hospital (Inselspital) and University of Bern, Bern, Switzerland

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.

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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1. Hepatic blood flow regulation but not oxygen extraction capability is impaired in prolonged experimental abdominal sepsis;American Journal of Physiology-Gastrointestinal and Liver Physiology;2022-10-01

2. A clinical approach to acute mesenteric ischemia;Current Opinion in Critical Care;2020-12-30

3. Defense mechanisms to increasing back pressure for hepatic oxygen transport and venous return in porcine fecal peritonitis;American Journal of Physiology-Gastrointestinal and Liver Physiology;2020-09-01

4. Mesenteric vascular dysregulation and intestinal inflammation accompanies experimental spinal cord injury;American Journal of Physiology-Regulatory, Integrative and Comparative Physiology;2017-01-01

5. Dynamic Contrast-Enhanced Ultrasound of Slaughterhouse Porcine Livers in Machine Perfusion;Ultrasound in Medicine & Biology;2014-09

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