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Cardioprotective actions of oligotide, a single stranded polydeoxyribonucleotide complex, in myocardial ischaemia and reperfusion injury
Author(s) -
Murohara Toyoaki,
Buerke Michael,
Lefer Allan M.
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16689.x
Subject(s) - medicine , endothelium , ischemia , coronary arteries , cardiology , cardioprotection , endothelial dysfunction , in vivo , p selectin , ex vivo , anesthesia , platelet , artery , platelet activation , microbiology and biotechnology , biology
1 The efficacy of oligotide, a single stranded polydeoxyribonucleotide complex, was examined in a feline model of myocardial ischaemia (MI: 90 min) and reperfusion (R: 270 min). Oligotide (15 mg kg −1 bolus) was administered intravenously 80 min after occlusion of the left anterior descending (LAD) coronary artery (i.e., 10 min prior to R) and continued for an additional 280 min (10 mg kg −1 h −1 infusion). 2 Oligotide‐treated cats showed significantly smaller myocardial necroses and lower cardiac myeloperoxidase activities (significantly lower neutrophil infiltration) in the necrotic zone as compared to MI + R cats receiving only vehicle. 3 LAD coronary arteries isolated from MI + R cats exhibited a significant endothelial dysfunction (i.e., reduced endothelium‐dependent relaxation), and significantly increased adherence of polymorphonuclear neutrophils (PMNs) ex vivo. However, oligotide significantly preserved endothelial function and attenuated PMN adherence in ischaemic LAD coronary arteries. 4 Oligotide attenuated P‐selectin expression on thrombin‐stimulated platelets as well as PMN adherence to thrombin‐stimulated coronary endothelium. Immunohistochemical examination in vivo revealed that oligotide treatment also significantly inhibited coronary endothelial P‐selectin expression after 90 min MI and 20 min R. 5 Oligotide exerted a significant cardioprotection in MI + R injury. The mechanism appears to be related to attenuation of PMN‐endothelial interaction and eventual infiltration into the ischaemic myocardium.