| Summary: | Liver transplantation is an accepted form of treatment
in advanced liver disease. The procedure qualifies as one
of the most severe surgical insults that can be inflicted
upon a patient. Despite an ever increasing number of
clinical and experimental transplants, a vast number of
unanswered questions remains about the effects of storage
and transplantation per se, on the functions of this
complex organ. The administration of drugs and blood, with
the effects of the donor state and preservation damage
obscure changes in parameters that are inherently due only
to the process of transplantation,
Changes in calcium and other electrolyte homeostasis,
liver function assessment, acid base metabolism and
coagulation defects that are seen after liver grafting, are
of particular interest to transplant physicians. Current
clinically employed indices of liver function, such as
enzyme levels, are notoriously lacking in specificity and
sensitivity,
The aim of the study was to investigate in the
experimental situation, the effects of standardised
preservation and transplantation, without the added effects
of blood transfusion or immunosuppressive drug
administration, upon calcium and other electrolyte
homeostasis, liver function and coagulation changes. Furthermore, reliable indicators of liver function and/or
damage were looked for. It was not an investigation into
preservation methods to determine superiority of one or
another of these methods, but an evaluation of changes
occurring utilising established and clinically proven
methods of preservation.
Since researchers in the J.S. Marais laboratory, as
well as their international counterparts, have experienced
problems in successful storage of the pig liver for periods
longer than 9 hours, a storage duration of six hours was
chosen for maximum reproducibility.
A brief overview of liver transplantation history has
been given, available literature perused and used in
assessment and discussion of data obtained.
Five groups of six animals were used for orthotopic
liver transplantation. Two groups were autografted with a
non-flushed and Ringers lactate flushed liver respectively.
Two groups were allografted with livers stored in Collins
and University of Wisconsin solutions respectively. A fifth
group was transplanted with a liver stored for six hours by
surface cooling alone, without any flushing at all. The
latter method has not been described in experimental or
clinical liver transplantation before. No immunosuppression
was used in any animal, to eliminate the effects of hepatotoxic drugs. No blood was transfused
at any point during or after the transplant. An animal
survival rate in excess of 90%, for seven days or longer,
was aimed for and obtained.
Blood sampling was done at short intervals in the
immediate postoperative period up to six hours and daily
for a week. All currently used clinical parameters were
determined, as well as indicators which are known, but
novel in transplantation.
Changes in total and ionised calcium values occurred
in all groups and no explanatory mechanism could be
identified. There was no correlation in changes between
total and ionised calcium, nor any correlation with calcium
content of preservation fluids. A reciprocal change in
magnesium was identified.
Acid base metabolism was markedly changed during and
after the transplant. An increase in serum bicarbonate
indicated survival, and a persisting metabolic alkalosis
was seen in all survivors. Sodium and potassium values did
not show marked changes, except for a temporary
hyperkalaemia immediately following reperfusion. Serum
values of liver transaminases were not found to be of value
to discriminate between groups. Protein metabolism was not
affected by transplantation. Glucose metabolism was
markedly affected by transplantation and even more so by poor function. Early return of normal glucose metabolism
indicated survival. Lactic acid metabolism was
conspicuously altered during transplantation and could also
be regarded as an indicator of hepatocyte function.
Coagulation in this series of experiments was affected
negligibly and not thought to be influenced by
transplantation of a normal liver under ideal
circumstances.
Thus, changes in values within groups and variance
between groups, if any, were described and possible
mechanisms causing variation discussed. New indicators of
good liver function post-transplant were identified.
The conclusion was reached that the process of
transplantation per se does cause major changes in
electrolyte and acid-base metabolism, but that coagulation
was not affected by the process of successful preservation
and transplantation.
|
|---|
