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T R Fernandes

Publications and source records attributed to T R Fernandes.

3 recordsLinked to original sources
PubMed1999

The heterogeneous response of the bivascularly perfused rat liver to adenosine.

The heterogeneity of the liver parenchyma in relation to the metabolic response to adenosine was investigated using the bivascularly perfused rat liver in the anterograde and retrograde modes. Adenosine was infused into livers from fed rats according to four experimental protocols: (A) anterograde perfusion, adenosine via the portal vein; (B) anterograde perfusion, adenosine via the hepatic artery; (C) retrograde perfusion, adenosine via the hepatic vein; and (D) retrograde perfusion, adenosine via the hepatic artery. Due to the very pronounced concentration gradients generated by metabolic transformation, the infused adenosine attained maximal concentrations in different regions with each experimental protocol. The sinusoidal mean transit times (t(s)) were not changed by adenosine in anterograde perfusion, but were increased in retrograde perfusion. It was concluded that the vasoconstrictive elements are localized essentially in the presinusoidal region. Glucose release stimulation presented two kinetic components. The first one was rapid in both onset and decay with a peak around 30 sec; the second one developed more slowly (several minutes). The factors of the first kinetic component are possibly generated in the presinusoidal region or in the first periportal cells. The initial decrease in oxygen consumption seemed to be localized in the region just after the intrasinusoidal confluence of the ramifications of the portal vein and hepatic artery. Indomethacin decreased glucose release stimulation by adenosine in both anterograde and retrograde perfusion only when DMSO was the vehicle. The participation of eicosanoids in the generation of the effects of adenosine seems to be less important than hitherto believed.

Adenosine↗
PubMed1999

Regional heterogeneities in the production of uric acid from adenosine in the bivascularly perfused rat liver.

The heterogeneity of the liver parenchyma in relation to uric acid production from adenosine was investigated using the bivascularly perfused rat liver in the anterograde and retrograde modes. Adenosine was infused in livers from fed rats during 20 min at four different concentrations (20, 50, 100 and 200 microM) according to four experimental protocols as follows: (A) anterograde perfusion, with adenosine infusion into the portal vein; (B) anterograde perfusion, with adenosine in the hepatic artery, (C) retrograde perfusion, with adenosine in the hepatic vein; (D) retrograde perfusion, with adenosine in the hepatic artery. With protocols A, B, and D uric acid production from adenosine was always characterized by initial bursts followed by progressive decreases toward smaller steady-states. With protocol C the initial burst was present only when 200 microM adenosine was infused. The initial bursts in uric acid production were accompanied by simultaneous increases in the ratio of uric acid production/adenosine uptake rate. These initial bursts are thus representing increments in the production of uric acid that are not corresponded by similar increments in the metabolic uptake rates of adenosine. Global analysis of uric acid production revealed that the final steady-state rates were approximately equal for all infusion rates with protocols A, B and C, but smaller with protocol D. This difference, however, can be explained in terms of the differences in accessible cellular spaces, which are much smaller when protocol D is employed. When the analysis was performed in terms of the extra amounts of uric acid produced during the infusion of adenosine, where the initial bursts are also taken into account, different dose-response curves were found for each experimental protocol. These differences cannot be explained in terms of the accessible cell spaces and they are likely to reflect regional heterogeneities. From the various dose-response curves and from the known characteristics of the microcirculation of the rat liver it can be concluded that the initial bursts in uric acid production are generated in periportal hepatocytes. The reason for this heterogeneity could be related to the metabolic effects of adenosine, especially to oxygen uptake inhibition, which is likely to produce changes in the ATP/AMP ratios.

Adenosine↗