Cardioprotective actions of oligotide, a single stranded polydeoxyribonucleotide complex, in myocardial ischaemia and reperfusion injury.
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.
Murohara
T
T
Department of Physiology, Thomas Jefferson University, Philadelphia, PA 19107-6799, USA.
Buerke
M
M
Lefer
A M
AM
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002415:Cats; D003331:Coronary Vessels / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D005434:Flow Cytometry; D006321:Heart / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy*; D009504:Neutrophils / Q000187:drug effects; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology / Q000627:therapeutic use*; D019007:P-Selectin / Q000032:analysis; D009195:Peroxidase / Q000032:analysis; D013917:Thrombin / Q000037:antagonists & inhibitors; D014664:Vasodilation
D009838:Oligodeoxyribonucleotides; D019007:P-Selectin; C099595:oligotide; D009195:Peroxidase; D013917:Thrombin; D000109:Acetylcholine