Cmcj. Vanhaaster et al., LACK OF EVIDENCE FOR A ROLE OF MAST-CELL DEGRANULATION IN ACUTE-HYPOXIA REOXYGENATION-INDUCED INJURY IN THE ISOLATED RAT-HEART, Journal of Molecular and Cellular Cardiology, 28(2), 1996, pp. 363-373
In the present study, we evaluated the potential role of mast cell deg
ranulation in acute hypoxia/reoxygenation-induced injury to cardiomyoc
ytes in the isolated rat heart, Histamine release was determined to de
lineate the extent of mast cell degranulation, whereas the release of
creatine kinase (CK) and lactate dehyrdrogenase (LDH) was assessed to
quantitate the extent of irreversible injury to cardiomyocytes, The su
itability of peroxidase (PO) as a marker for mast cell degranulation w
as also evaluated. Reoxygenation resulted in a release of histamine co
rresponding with 6.5%+/-0.6% of total tissue content, whereas LDH, CK
and PO release amounted to 30%+/-2%, 28%+/-2% and 32%+/-3% of their re
spective tissue contents. Identical perfusion in the presence of the m
ast cell stabilizer lodoxamide tromethamine resulted in a reduced hist
amine release (2.8%+/-0.1%) of total tissue content upon reoxygenation
, but the release of LDH, CK or PO was not influenced. Cumulative hist
amine release did not correlate with the amount of LDH, CK or PO relea
sed, Treatment with consecutive bolus injections of the mast cell degr
anulating compound 48/80 during normoxic perfusion resulted in an almo
st complete histamine release, whereas PO release remained below detec
tion limit. When the compound 48/80-treated hearts were subjected to h
ypoxia/reoxygenation, the release of LDH, CK or PO during reoxygenatio
n again remained unchanged, whereas histamine release was negligible.
Determination of PO activity of freshly isolated cardiomyocytes demons
trated that the bulk of PO in rat hearts was located in this particula
r cell type. Therefore we conclude that in the isolated rat heart, PO
release is not a specific marker of mast cell degranulation. In additi
on, our data provide no firm evidence that in this experimental model,
mast cell degranulation contributes to a significant extent to acute
hypoxia/reoxygenation-induced injury to cardiomyocytes. (C) 1996 Acade
mic Press Limited