LACK OF EVIDENCE FOR A ROLE OF MAST-CELL DEGRANULATION IN ACUTE-HYPOXIA REOXYGENATION-INDUCED INJURY IN THE ISOLATED RAT-HEART

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