Hepatic blood flow in adult Göttingen minipigs and pre-pubertal Danish Landrace x Yorkshire pigs

The liver receives dual blood supply from the hepatic artery and portal vein. The pig is often used as an animal model in positron emission tomography (PET) and pharmacokinetic studies because of the possibility for extensive and direct blood sampling. In this study, we compared measurements of hepatic blood flow in 10 female adult Göttingen minipigs and 10 female pre-pubertal Danish Landrace x Yorkshire (DLY) pigs. Ultrasound transit time flow meter probes were placed around the hepatic artery and portal vein through open surgery, hepatic blood flow measurements were performed, and the liver was weighed. Total hepatic blood flow was on average 363 ± 131 mL blood/min in Göttingen minipigs and 988 ± 180 mL blood/min in DLY pigs ( p < 0.001). The mean hepatic blood perfusion was 623 mL blood/min/mL liver tissue and 950 mL blood/min/mL liver tissue ( p = 0.005), and the liver weight was 0.58 kg and 1.04 kg, respectively. The mean arterial flow fraction in Göttingen minipigs was 12 ± 7% and lower than in DLY pigs, where it was 24 ± 7% ( p = 0.001). Using the gold standard for blood flow measurements, we found that both total hepatic blood flow and blood perfusion were significantly lower in Göttingen minipigs than in DLY pigs. The hepatic blood perfusion and arterial flow fraction in DLY pigs were comparable to normative values from humans. Differences in hepatic blood flow between adult Göttingen minipigs and humans should be considered when performing physiological liver studies in this model.

Active and passive liver microvascular responses from angiotensin, endothelin, norepinephrine, and vasopressin

Vasoconstrictor agents may induce a decrease in hepatic vascular volume passively, by decreasing distending pressure, or actively, by stimulating contractile elements of capacitance vessels. Hepatic venular resistance was estimated in anesthetized rabbits from hepatic venular pressure (Pμhv; by servo-null micropipette), inferior vena cava pressure, and total hepatic blood flow (Fhv; by ultrasound flow probe). Changes in liver volume were estimated from measures of liver lobe thickness. Angiotensin (ANG) II, endothelin (ET)-1, norepinephrine (NE), and vasopressin (VP) were infused into the portal vein at a constant rate for 5 min. We conclude that ANG II and NE induced active constriction of hepatic capacitance vessels, because the liver lobe thickness decreased significantly even though Pμhv and portal venous distending pressure (Ppv) increased. All four agents increased splanchnic and hepatic venous resistances in similar proportions. With VP, Pμhv and Ppv decreased, but with ET-1, Pμhv and Ppv increased. However, lobe thickness was not significantly changed by either drug during the infusion compared with the 2-min control period. Thus VP and ET-1 have only minor effects on hepatic capacitance vessels. ET-1, at 0.04 μg · min−1 · kg body wt−1, caused an increase in systemic arterial blood pressure, but erythrocyte movement through the sinusoids in some animals stopped.

Effects of abdominal CO2insufflation and changes of position on hepatic blood flow in anesthetized pigs

During surgical laparoscopy, total hepatic blood flow (THBF) may be modified by CO2insufflation, changes of tilt, ventilation with high tidal volume, hypercapnia, and anesthesia, but little information is available on the THBF during the procedure. To investigate the changes of hepatic blood flow following the combination of abdominal CO2 insufflation and changes of tilt, we measured mean arterial pressure (MAP), cardiac output, portal vein blood flow (PVBF), and hepatic artery blood flow (HABF) in anesthetized and ventilated pigs. CO2 was insufflated in the abdomen [intra-abdominal pressure (IAP) ∼15 mmHg], and the hepatic blood flow was measured in various positions (horizontal, 10° and 20° head down, and 10° and 20° head up) before and during CO2 insufflation. CO2 insufflation in the horizontal position did not modify MAP, cardiac output, or PVBF but increased HABF. The head-up tilt decreased MAP, cardiac output, and both hepatic flows in the absence of pneumoperitoneum, but in the presence of abdominal CO2 only cardiac output and PVBF were decreased. The head-down tilt increased MAP and THBF in the absence of pneumoperitoneum, whereas no change was observed in the presence of abdominal CO2. The combination of CO2 insufflation and changes of tilt was not deleterious to hepatic perfusion. These results suggest that hepatic blood flow may be preserved during surgical laparoscopy if the tilt does not exceed 20° and if IAP after CO2 insufflation remains <15 mmHg.

Hepatic venular resistance responses to norepinephrine, isoproterenol, adenosine, histamine, and ACh in rabbits

Changes in hepatic venous resistance were estimated in rabbits from the hepatic venular-inferior vena caval pressure gradient [servo-null micropipettes in 49 ± 15 (SD) μm vessels] and the total hepatic blood flow (ultrasound probe encircling the hepatic artery and the portal vein). Changes in liver volume, and thus vascular capacitance, were estimated from measures of the liver lobe thickness. Norepinephrine (NE), isoproterenol (Iso), adenosine (Ado), histamine (Hist), or acetylcholine (ACh) was infused into the portal vein at a constant rate for 5 min. NE, Hist, and Ado increased hepatic venular pressure, but only NE and Hist significantly increased hepatic venular resistance. NE reduced the liver thickness, but Hist and Ado caused engorgement. Hepatic blood flow was increased by NE and Ado and decreased by ACh. The influence of intraportal vein infusion of Iso on the liver vasculature, at doses similar to that of NE, was insignificant. We conclude that NE acted on all the hepatic microvasculature, increasing resistance and actively decreasing vascular volume. Hist passively induced engorgement by increasing outflow resistance, whereas the liver engorgement seen with Ado was passively related to the increased blood flow. ACh constricted the portal venules but did not change the liver volume.

Changes in Hepatic Hemodynamics due to Primary Liver Tumours

Data regarding the afferent circulation of the liver in patients with primary hepatocellular carcinoma are controversial, we have carried out measurement of hepatic arterial and portal venous flow intraoperatively by transit time ultrasonic volume flowmetry. In patients with primary hepatocellular carcinoma the hepatic artery flow increased to 0.55±0.211 compared with the control value of 0.37±0.102 1/min. (p<0.01). The portal venous flow decreased from 0.61±0.212 l/min, to 0.47±l/min. p<0.01). Due to the opposite changes in the afferent circulation the total hepatic blood flow did not change significantly, compared with controls.The ratio of hepatic arterial flow to portal vein flow increased to 1.239±0.246 in patients with hepatocellular carcinoma, which is double of the control value (0.66±0.259 l/min). After resection this ratio did not change.The resection did not alter hepatic artery or portal venous flow significantly, although the total hepatic blood flow decreased significantly (p<0.01).On the basis of our early results it is possible that the ratio of the two circulations may be to deel measured with doppler ultrasound and provide diagnostic information.

Influence of plane of nutrition on portal blood flow and the metabolic clearance rate of progesterone in ovariectomized gilts

SUMMARYThe effects of plane of nutrition on blood flow in the portal vein (PBF) and on the rate of clearance of progesterone from the circulation (MCR) were measured for 14 or 24 h in six ovariectomized gilts given 1 or 3 kg of food per day. On a body weight basis, PBF was significantly increased by the increase in food intake from a mean for all gilts of 14·9 ml/kg.min (1·34 litres/min) on 1 kg to 21·6 ml·kg. min (1·96 litres/min) on 3 kg, a mean increase of 45 %. Metabolic clearance of progesterone was increased by a similar percentage, 47·1%, from 41·0 ml/kg.min (3·70 litres/min) to 60·3 ml/kg.min (5·67 litres/min) by the increase in food intake. Both MCR and PBF were lowest between 04.00 and 06.00 h, increasing after each feed except that when 3 kg/day was fed the MCR remained high throughout the period between meals. In two gilts, blood flow in both the portal vein and hepatic artery (HAF) was measured. The mean PBF and HAF for each pig were 40·6 and 5·8, and 32·4 and 35 ml/kg, min respectively. HAF was 11·2% of total hepatic blood flow.