Immunological challenge with virus initiates leukotriene C4 production in the heart and induces cardiomyolysis in guinea pigs.
Cardiac myolysis was observed in guinea pigs sensitized with vesicular stomatitis virus (VSV), following challenge with this antigen. The phenomenon developed within 1 h of challenge, appearing as islands in the myocardium. The speed and focal nature of the damage point to obstruction of blood flow as a cause of the myolysis. The myolysis was not a toxic effect of the virus itself, but probably a consequence of cardiac anaphylaxis. It occurred only after challenge, and was abolished in 71% of the animals by pretreatment with a mixture of the lipoxygenase-cyclooxygenase inhibitor, BW755C and H1 histamine receptor antagonist, diphenhydramine. Treatment with BW755C alone before challenge prevented myolysis from developing in 46% of the animals. Challenge in vitro with VSV to the perfused, spontaneously beating, sensitized isolated guinea pig heart increased sulfidopeptide-leukotriene (LTC4, LTD4, LTE4) production from undetectable levels (0.5 ng LTD4-equivalent/heart/15' to 13 ng LTD4-equivalent/heart/15'. At the same time, there were derangements in cardiac rate, contractility and coronary outflow typical of cardiac anaphylaxis. The reduction in coronary outflow rate during cardiac anaphylaxis is due largely to the powerful vasoconstrictor effect of LT, as well as perhaps platelet-activating-factor. Thus it is speculated that there is a causal relationship between LT release, vasoconstriction, ischemia and myolysis in the heart, following VSV challenge to sensitized guinea pigs.
D000707:Anaphylaxis / Q000209:etiology; D000818:Animals; D000937:Antigen-Antibody Reactions; D000956:Antigens, Viral / Q000008:administration & dosage; D009202:Cardiomyopathies / Q000209:etiology* / Q000473:pathology; D003326:Coronary Circulation; D003327:Coronary Disease / Q000209:etiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D013189:SRS-A / Q000096:biosynthesis*; D014721:Vesicular stomatitis Indiana virus / Q000276:immunology*
D000956:Antigens, Viral; D013189:SRS-A