Acute reoxygenation injury in the isolated rat heart: role of resident cardiac mast cells.
Leukocyte-mediated myocardial reperfusion injury is characterized by the progressive migration and accumulation of polymorphonuclear leukocytes within the myocardium. In this study, we hypothesized that leukocytes normally resident to the myocardium also contribute to myocardial injury in the absence of migration and accumulation of peripheral polymorphonuclear leukocytes. In isolated crystalloid-perfused rat hearts, we found numerous resident cardiac leukocytes that were identified primarily as macrophages and mast cells, the latter staining avidly for peroxidase. When hypoxic perfused hearts (60 minutes, n = 16) were reoxygenated there was a prompt release of this peroxidase activity, the extent of which correlated closely with the degree of myocardial injury (total creatine kinase release, r = 0.96). When reoxygenation associated mast cell degranulation was prevented in six additional hypoxic hearts using 10 microM Lodoxamide Tromethamine, peroxidase release was reduced 7.8-fold (p less than 0.001) and creatine kinase release (injury) was reduced 5.9-fold (p less than 0.001). These results demonstrate that the isolated crystalloid-perfused rat heart is not a leukocyte-free preparation and suggest that mast cells resident to the heart play an important role in acute reoxygenation injury.
Keller
A M
AM
Department of Medicine, University College of Physicians and Surgeons.
Clancy
R M
RM
Barr
M L
ML
Marboe
C C
CC
Cannon
P J
PJ
D000208:Acute Disease; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D003402:Creatine Kinase / Q000378:metabolism; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007962:Leukocytes / Q000145:classification / Q000473:pathology; D008297:Male; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D015428:Myocardial Reperfusion Injury / Q000473:pathology*; D009206:Myocardium / Q000473:pathology*; D009570:Nitriles; D010072:Oxamic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014325:Tromethamine / Q000031:analogs & derivatives / Q000494:pharmacology
D015415:Biomarkers; D009570:Nitriles; D014325:Tromethamine; C022028:lodoxamide tromethamine; D009195:Peroxidase; D003402:Creatine Kinase; D010072:Oxamic Acid