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Increased sinusoidal flow is not the primary stimulus to liver regeneration.

Mortensen KE, Conley LN, Nygaard I, Sorenesen P, Mortensen E, Bendixen C, Revhaug A - Comp Hepatol (2010)

Bottom Line: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis.Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%).Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Research Laboratory, Institute of Clinical Medicine, University of Tromsoe, Tromsoe, Norway.

ABSTRACT

Background: Hemodynamic changes in the liver remnant following partial hepatectomy (PHx) have been suggested to be a primary stimulus in triggering liver regeneration. We hypothesized that it is the increased sinusoidal flow per se and hence the shear-stress stimulus on the endothelial surface within the liver remnant which is the main stimulus to regeneration. In order to test this hypothesis we wanted to increase the sinusoidal flow without performing a concomitant liver resection. Accordingly, we constructed an aorto-portal shunt to the left portal vein branch creating a standardized four-fold increase in flow to segments II, III and IV. The impact of this manipulation was studied in both an acute model (6 animals, 9 hours) using a global porcine cDNA microarray chip and in a chronic model observing weight and histological changes (7 animals, 3 weeks).

Results: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis. Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%). Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

Conclusions: An isolated increase in sinusoidal flow does not have the same genetic, microscopic or macroscopic impact on the liver as that seen in the liver remnant after partial hepatectomy, indicating that increased sinusoidal flow may not be a sufficient stimulus in itself for the initiation of liver regeneration.

No MeSH data available.


Related in: MedlinePlus

Experimental setup. In the acute series, flow and pressure in all vascular structures to the liver were recorded continuously for the whole experiment. In the chronic series, flow in the aortoportal shunt was recorded upon establishment and after three weeks upon relaparatomy.
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Figure 1: Experimental setup. In the acute series, flow and pressure in all vascular structures to the liver were recorded continuously for the whole experiment. In the chronic series, flow in the aortoportal shunt was recorded upon establishment and after three weeks upon relaparatomy.

Mentions: Fig. 1 displays the experimental setup. All experiments were conducted in compliance with the institutional animal care guidelines and the National Institute of Health's Guide for the Care and Use of Laboratory Animals [DHHS Publication No. (NIH) 85-23, Revised 1985]. A total of nineteen pigs were used (Sus scrofa domesticus), aged approximately 3 months; twelve in the acute experiments, with an average weight of 33.5 kg (± 2 kg) and seven in the chronic experiments, with an average weight of 31.0 kg (± 2 kg). In the acute series, we followed the same anesthesia protocol as previously described [21]. In the chronic series, anesthesia for the surgical intervention was maintained with isoflurane 1.5-2% mixed with 55% oxygen. Respiratory rate was adjusted to achieve an Et CO2 between 3.5 and 6 KPa. Mean alveolar concentration of isoflurane was maintained at 1.3 using a Capnomac (Nycomed Jean Mette). Analgesia was induced and maintained with fentanyl 0.01 mg/kg. Before surgery, all animals received a single i.m. shot of antibiotic prophylaxis (Enrofloxacin, 2.5 mg/kg).


Increased sinusoidal flow is not the primary stimulus to liver regeneration.

Mortensen KE, Conley LN, Nygaard I, Sorenesen P, Mortensen E, Bendixen C, Revhaug A - Comp Hepatol (2010)

Experimental setup. In the acute series, flow and pressure in all vascular structures to the liver were recorded continuously for the whole experiment. In the chronic series, flow in the aortoportal shunt was recorded upon establishment and after three weeks upon relaparatomy.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2819042&req=5

Figure 1: Experimental setup. In the acute series, flow and pressure in all vascular structures to the liver were recorded continuously for the whole experiment. In the chronic series, flow in the aortoportal shunt was recorded upon establishment and after three weeks upon relaparatomy.
Mentions: Fig. 1 displays the experimental setup. All experiments were conducted in compliance with the institutional animal care guidelines and the National Institute of Health's Guide for the Care and Use of Laboratory Animals [DHHS Publication No. (NIH) 85-23, Revised 1985]. A total of nineteen pigs were used (Sus scrofa domesticus), aged approximately 3 months; twelve in the acute experiments, with an average weight of 33.5 kg (± 2 kg) and seven in the chronic experiments, with an average weight of 31.0 kg (± 2 kg). In the acute series, we followed the same anesthesia protocol as previously described [21]. In the chronic series, anesthesia for the surgical intervention was maintained with isoflurane 1.5-2% mixed with 55% oxygen. Respiratory rate was adjusted to achieve an Et CO2 between 3.5 and 6 KPa. Mean alveolar concentration of isoflurane was maintained at 1.3 using a Capnomac (Nycomed Jean Mette). Analgesia was induced and maintained with fentanyl 0.01 mg/kg. Before surgery, all animals received a single i.m. shot of antibiotic prophylaxis (Enrofloxacin, 2.5 mg/kg).

Bottom Line: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis.Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%).Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgical Research Laboratory, Institute of Clinical Medicine, University of Tromsoe, Tromsoe, Norway.

ABSTRACT

Background: Hemodynamic changes in the liver remnant following partial hepatectomy (PHx) have been suggested to be a primary stimulus in triggering liver regeneration. We hypothesized that it is the increased sinusoidal flow per se and hence the shear-stress stimulus on the endothelial surface within the liver remnant which is the main stimulus to regeneration. In order to test this hypothesis we wanted to increase the sinusoidal flow without performing a concomitant liver resection. Accordingly, we constructed an aorto-portal shunt to the left portal vein branch creating a standardized four-fold increase in flow to segments II, III and IV. The impact of this manipulation was studied in both an acute model (6 animals, 9 hours) using a global porcine cDNA microarray chip and in a chronic model observing weight and histological changes (7 animals, 3 weeks).

Results: Gene expression profiling from the shunted segments does not suggest that increased sinusoidal flow per se results in activation of genes promoting mitosis. Hyperperfusion over three weeks results in the whole liver gaining a supranormal weight of 3.9% of the total body weight (versus the normal 2.5%). Contrary to our hypothesis, the weight gain was observed on the non-shunted side without an increase in sinusoidal flow.

Conclusions: An isolated increase in sinusoidal flow does not have the same genetic, microscopic or macroscopic impact on the liver as that seen in the liver remnant after partial hepatectomy, indicating that increased sinusoidal flow may not be a sufficient stimulus in itself for the initiation of liver regeneration.

No MeSH data available.


Related in: MedlinePlus