RICERCA ITALIANA     

TISSUTAL METABOLISM AND GENIC EXPRESSION: NEWS PERSPECTIVES IN SURGERY

Università degli Studi dell'Insubria Varese-Como

Abstract

Sperimental Phase:
-General Surgery
Foresee the use of intraparenchimal microdialisys to identify and quantify directly the entity of cellular damage into the interstitial
hepatic space.The implement of a sperimental study in the swine concerning the effects of hepatic preservation with predetermined ischemic damage levels. The evaluation of relation between ischemic damage, tolerance induction and survival. Foresee to set a sperimental model of colo-rectal surgery in the mouse, to verify the potential measurement of studying parameters (piruvate, lactate, glucose, glycerol) in peritoneal fluid withdrawed by microdialisys.
Clinical phase:
-Vascular surgery
The aim of our study will be to assess the extracellular metabolism of patients affected by critical limb ischemia, who underwent surgical revascularization or endovascular revascularization.
-Vascular Biology
In this context, the main aim of the present study will be to investigate the metabolism of leukocytes and endothelial cells (with particular regard to parameters directly related to the regulation of the inflammatory process and of ATH, and to the role of Ang II) in subjects candidate to surgery for peripheral revascularization.

Principal Investigator

Renzo DIONIGI Università degli Studi INSUBRIA Varese-Como

Research Objectives

The aim of this work is the study of the cellular methabolism different districts and organs involved by surgical procedure.

Sperimental Phase
As we previously said, hepatic regeneration after liver resection is a well known event. Hepatocites, usually in G0 phase, are
stimulated to move into G1 phase and to start proliferating; what and why this phenomenon happen it is still unclear.
It is very likely that specific growth factrs such as EGF, PGF etc, produced locally or carried by the portal system, may stimulatehepatic cells to proliferate and to compensate the resected parenchyma. In order to measure the amount of liver regeneration several techniques have been proposed (see ahead); among them immunohystochemical mesurament of Ki67 cell's expression seem to be aneasy and precise methods. Microdialysis seems to be an optimal technique to collect interstitial fluids of the studied organ, and to measure different molecules such ad ODFR, markers of ischemia and cell damage as well ad growth factors.
The aims of the study are to evaluate the ODFR, markers of cell damages and growth factors production during liver ischemia and reperfusion with different type of ilar clamping, liver regeneration, using intra-parenchymal microdyalisis in rats
Aim of the Study
The above research have the following aims:
1) To continuously monitor and measure the intra-parenchymal production ODFR, markers of cell membrane destruction >>>

Timescale

24 months

National and international background

Principles of Microdialysis
Microdialysis is a way to examine the interstitial space of intact tissue. The microdialysis unit is a semipermeable membrane which is perfused with a neutral solution using a high performance pump. The microdialysis catheter is placed in the interstitial space of the tissue to be examined. Small molecules can pass in and out of the membrane during perfusion. The ingoing and outgoing microdialysate can be compared. The net changes reflect what is happening in the interstitial space. Microdialysis catheters, designed for use in man, are now available from CMA/Microdialysis. The catheters can easily be inserted in human fat and muscle tissues and the metabolism in these tissues can be investigated.
Studies of metabolite levels in peripheral tissues: Microdialysis can be used to continuously monitor changes in the concentration of various metabolises in adipose tissue and muscle. In particular glucose, lactate and pyruvate (reflecting carbohydrate metabolism) and glycerol (reflecting lipid breakdown through lipolysis) have been investigated. It is also possible to study other small molecules which easily move through the membrane such as adenosine, urea and amino acids. It is possible to determine the true interstitial concentration of various metabolises with microdialysis. One way is to perfuse the tissue at a high speed (1 -5 ml/min) with increasing concentrations of the metabolite to be determined. The differences in the >>>