title: Lack of evidence for a role of mast cell degranulation in acute hypoxia/reoxygenation-induced injury in the isolated rat heart.
abstract: In the present study, we evaluated the potential role of mast cell degranulation in acute hypoxia/reoxygenation-induced injury to cardiomyocytes in the isolated rat heart. Histamine release was determined to delineate the extent of mast cell degranulation, whereas the release of creatine kinase (CK) and lactate dehydrogenase (LDH) was assessed to quantitate the extent of irreversible injury to cardiomyocytes. The suitability of peroxidase (PO) as a marker for mast cell degranulation was also evaluated. Reoxygenation resulted in a release of histamine corresponding 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 respective tissue contents. Identical perfusion in the presence of the mast cell stabilizer lodoxamide tromethamine resulted in a reduced histamine release (2.8% +/- 0.1%) of total tissue content upon reoxygenation, but the release of LDH, CK or PO was not influenced. Cumulative histamine release did not correlate with the amount of LDH, CK or PO released. Treatment with consecutive bolus injections of the mast cell degranulating compound 48/80 during normoxic perfusion resulted in an almost complete histamine release, whereas PO release remained below detection limit. When the compound 48/80-treated hearts were subjected to hypoxia/reoxygenation, the release of LDH, CK or PO during reoxygenation again remained unchanged, whereas histamine release was negligible. Determination of PO activity of freshly isolated cardiomyocytes demonstrated that the bulk of PO in rat hearts was located in this particular cell type. Therefore we conclude that in the isolated rat heart, PO release is not a specific marker of mast cell degranulation. In addition, 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.
authors.affiliation: Cardiovascular Research Institute Maastricht, University of Limburg, Netherlands.
authors.forename: C M
authors.initials: CM
authors.lastname: van Haaster
authors.forename: W
authors.initials: W
authors.lastname: Engels
authors.forename: A M
authors.initials: AM
authors.lastname: Duijvestijn
authors.forename: P J
authors.initials: PJ
authors.lastname: Lemmens
authors.forename: G
authors.initials: G
authors.lastname: Hornstra
authors.forename: G J
authors.initials: GJ
authors.lastname: Van der Vusse
mesh_terms: D000208:Acute Disease; D000818:Animals; D015550:Cell Degranulation / Q000502:physiology*; D015687:Cell Hypoxia / Q000502:physiology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006636:Histamine Release; D066298:In Vitro Techniques; D008297:Male; D008407:Mast Cells / Q000502:physiology*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology; D010100:Oxygen / Q000009:adverse effects*; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D003189:p-Methoxy-N-methylphenethylamine / Q000494:pharmacology
chemical_list: D003189:p-Methoxy-N-methylphenethylamine; D009195:Peroxidase; D010100:Oxygen