Modulation of hepatocyte growth factor plasma levels in relation to the dose of exogenous heparin administered: an experimental study in rats.
BACKGROUND
Partial liver transplantation has been consolidated to be a valid treatment option. We sought to understand the factors that modulate and may be harnessed to accelerate hepatocyte regeneration. We sought to determine the impact of heparin on m-hepatocyte growth factor (HGF) plasma concentrations.


METHODS
Sixteen rats were assigned to four groups of four animals each: group A, without heparin; group B, 600 IU/kg; group C, 1000 IU/kg, group D, 1400 IU/kg. Blood samples (0.5 mL) were obtained from each rat at baseline and at 30, 60, 120, and 240 minutes. After the samples were centrifuged to separate supernates from the cell phase they were stored at -20 degrees C in the m-HGF reagent and subsequently tested using enzyme-linked immunosorbent assay. Results were analyzed using SPSS 11.5 statistical software.


RESULTS
Among the 16 rats, one died at 110 minutes, just prior to the last extraction. The remaining rats were sacrificed. Mean weight was: 466 +/- 64.24 g with no intergroup differences (P = .149). The comparative results (using Student t test) were: baseline A(1-4) versus A(1-4) 30 minutes: P < .05; baseline A(1-4) versus A(1-4) 60 minutes: P < .05; baseline A(1-4) versus A(1-4) 120 minutes: P = .10 (NS); baseline A(1-4) versus A(1-4) 240 minutes: P = .15 (NS). No significant differences were found among group B: baseline C(1-4) versus C(1-4) 30 minutes and 60 minutes: NS; baseline C(1-4) versus C(1-4) 120 minutes: P < .001; baseline C(1-4) versus C(1-4) 240 minutes: P < .10 (NS). Finally, the results in group D were: baseline D(1-4) versus D(1-4) 30 minutes: NS; baseline D(1-4) versus D(1-4) 60 minutes and 120 minutes: P < .05; baseline D(1-4) versus D(1-4) 240 minutes: P < .0005. When we compared group A to C and D, we detected differences (albeit not when compared to B) with P values = .01. Peak values were obtained at 120 and 240 minutes (225.21 pg/mL and 221.78 pg/mL) among groups C and D.


CONCLUSIONS
Heparin has a positive effect to increase serum HGF concentrations among rats. The effect was dependent on the administered dose and the time elapsed.
Moreno
E
E
Jefe del Servicio de Chirugía Gral, Apto Digestivo y Transplante de Organos Abdominales, Hospital Universitario 12 de Octubre, Madrid, Spain. jcalvopulido@yahoo.es
Meneu
J C
JC
Calvo
J
J
Pérez
B
B
Sesma
A G
AG
Manrique
A
A
Vegh
I
I
Aragón
A M
AM
Grau
M
M
Gimeno
A
A
Jiménez
C
C
Gómez
R
R
Moreno
A
A
Abradelo
M
M
García
I
I
de la Calle
A
A
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006493:Heparin / Q000494:pharmacology*; D017228:Hepatocyte Growth Factor / Q000096:biosynthesis / Q000097:blood*; D007700:Kinetics; D008099:Liver / Q000502:physiology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D013997:Time Factors
D017228:Hepatocyte Growth Factor; D006493:Heparin