Takala J. Effects of cardiac preload reduction and dobutamine on hepatosplanchnic blood flow regulation in porcine endotoxemia. Am J Physiol Gastrointest Liver Physiol 303: G247-G255, 2012. First published May 3, 2012 doi:10.1152/ajpgi.00433.2011.-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 ϭ 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 g/kg per minute or another vehicle (n ϭ 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 Ϯ 11 mmHg vs. 58 Ϯ 8 mmHg (mean Ϯ SD); P ϭ 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 ϭ 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 ϭ 0.031; constriction-timegroup 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 ϭ 0.043) vs. 17% (Ϫ7-32%) in endotoxemia (P ϭ 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. hepatic arterial buffer response; sepsis; liver INADEQUATE SPLANCHNIC PERFUSION is associated with multiple organ failure and death (11, 23), especially when hepatic dysfunction is present (28). Global hepatic blood flow is supposed to be relatively protected when gut blood flow decreases because hepatic arterial flow increases when portal venous flow decreases (the hepatic arterial buffer response, HABR) (25, 26). However, evidence suggests that the HABR is diminished or even abolished during endotoxemia (1) and when gut blood flow becomes very low (19,31).The HABR is usually assessed by decreasing superior mesenteric or portal venous blood flow and measurement of ...