Aneurysm Papers of the Month - August 1995

A rather quiet month so far, but its only the 9th.  It
gives me an opportunity (since I'm going on vacation next
week), to take advantage of the moment and go back to the
fall of 1994 for three papers that would have made the
hit parade had I been doing this review at that time.  

1. Szekanecz Z, Shah MR, Pearce WH, Koch AE.  Human
atherosclerotic abdominal aortic aneurysms produce
interleukin (IL)-6 and interferon-gamma, but not IL-2 and
IL-4: the possible role for IL-6 and interferon-gamma in
vascular inflammation.  Agents and Actions.  1994; 42:
159-62.

Abstract (condensed from authors): 

     Background: Inflammatory leukocytes invade the AAA
wall and produce cytokines which perpetuate the immune
events that cause this disease.  IL-1 beta, IL-8, TNF-
alpha, and monocyte chemoattractant protein-1, among
others, may play a role.  The aim of this study was to
investigate the possible role of other cytokines: IL-2,
IL-4, IL-6 and interferon-gamma (IFN-g).

     Methods:  ELISA assays of human explant
supernatants.

     Results:  IFN-g production by AAA was significantly
increased over levels in atherosclerotic occlusive (AOD)
and normal (NL) explants.  IL-6 was also increased in AAA
compared to NL.  IL-2 and IL-4 were not detected.  

     Conclusion:  IL-6 (involved in T and B cell
activation) and IFN-g (which also stimulates T and B cells,
along with macrophages, endothelial cells and fibroblasts) 
may play roles in the pathogenesis of AAA.

Comment by mdt:  This paper is rather interesting in the
context of the T-helper 1 (TH1) versus T-helper 2 (TH2)
responses that are presently much-discussed in relation to
autoimmune diseases like rheumatoid arthritis.  T-zero 
cells are hypothesized to commit to one of two routes.
T-1 cells synthesize IL-2, interferon-g, and tumor 
necrosis factor (TNF); in other words, they become cytotoxic
T cells.  T-2 cells synthesize IL-4,5,6,10, and 12, becoming
"professional" T-helper cells, regulating class-switching
and other features of the B-cell response.  From work in
our own laboratory, we believe that both cytotoxicity and
humoral immunity occur in the AAA.  Thus, it is interesting 
in the present study that cytokines have been identified 
in explant cultures that are markers for both TH1 & 2 responses.



2.  Ramsbottom D, Fitzgerald P, Grace PA, et al. 
Biochemical and molecular genetic studies of abdominal
aortic aneurysm in an Irish population.  European J Vasc
Surg  1994; 8: 716-22.

Abstract (condensed from authors): 

     Background:  A gene on chromosome 16 has been
implicated as linked to a AAA-susceptibility locus. 
Also, differences in serum lipids, leukocyte elastase,
and alpha-1 antitrypsin have been suggested as risk
factors.  82 Irish AAA patients were studied, along with
79 age- and sex-matched control subjects.

     Methods: PCR was used to screen the patient and
control groups in search of disease-associated genetic
variation on chromosome 16 (particulary in the region of
the CETP gene).  Routine biochemical studes were used to
investigate the other potential risk factors.


     Results:  Four marker loci were studied by PCR, and
no significant gene-disease associations were detected. 
No significant differences were observed between patients
and control subjects in relation to serum lipids,
leukocyte elastase, or serum alpha-l antitrypsin
concentration.

     Conclusion:  The markers examined are of no
predictive value (in Ireland).

Comment by mdt.   Goodbye to chromosome 16 (at least in
Ireland), serum lipids, leukocyte elastase.......

3. Adembri C, Domenici LL, Formigli L, Brunelleschi S,
Ferrari E, Novelli GP.  Ischemia-reperfusion of *human*
skeletal muscle during aortoiliac surgery: effects of
acetylcarnitine. (*emphasis* by mdt) Histology & 
Histopathology  1994; 9: 683-90.

     Background: Previous studies by the authors on human
skeletal muscle suggest that granulocytes infiltrate in
large numbers and produce injurious superoxide anion (O2-)
during ischemia and reperfusion.  The present study was
carried out in 5 subjects to study the effect of an IV
dose of acetyl-carnitine (AC) given prior to ischemia
during surgery.

     Methods:  Muscle biopsies and blood samples were
taken at baseline, end-ischemia, and 30 min after
reperfusion.  

     Results:  AC did not prevent recruitment of
granulocytes into muscle tissue, but it did appear to
block their ability to generate O2-.  Morphological
changes were substantially reduced; in fact, the
mitochondrial swelling was only moderate and the
intramitochondrial dense bodies were small and scarce.

     Conclusion: AC appears to play a role in
ameliorating ischemia-reperfusion damage to human
skeletal muscle.


Comment by mdt:  Hey, Hobson, and all you other ischemia-
reperfusion mavens, how about this !  It suggests to me
that a sabbatical in Italy might offer interesting
opportunities to advance knowledge of ischemia-
reperfusion in the human species.