Cardioprotective effect induced by brief exposure to nitric oxide before myocardial ischemia-reperfusion in vivo.
Administration of nitric oxide (NO) donors during ischemia and reperfusion protects from myocardial injury. However, whether administration of an NO donor during a brief period prior to ischemia protects the myocardium and the endothelium against ischemia-reperfusion injury in vivo is unknown. To study this possibility anesthetized pigs were subjected to 45-min ligation of the left anterior descending coronary artery (LAD) followed by 4h of reperfusion. In initial dose-finding experiments, vehicle or three different doses of the NO donor S-nitroso-N-acetyl-D,L-penicillamin (SNAP; 0.1; 0.5; 2.5 micromol) were infused into the LAD for 3 min starting 13 min during ischemia. Only the 0.5 micromol dose of SNAP reduced infarct size (from 85+/-3% of the area at risk in the vehicle group to 63+/-3% in the SNAP-treated group; p<0.01). There were no significant differences in hemodynamics in the vehicle and SNAP groups during ischemia-reperfusion. Endothelium-dependent dilatation of coronary microvasculature induced by substance P was larger in the SNAP group than in the vehicle group. Myeloperoxidase activity was lower in the ischemic/reperfused myocardial area of pigs given SNAP (4.97+/-0.61 U/g) than in vehicle-treated pigs (8.45+/-0.25 U/g; p<0.05). It is concluded that intracoronary administration of the NO donor SNAP for a brief period before ischemia reduces infarct size, attenuates neutrophil accumulation, and improves endothelial function. These results suggest that NO exerts a classic preconditioning-like protection against ischemia-reperfusion injury in vivo in a narrow concentration range.
Gourine
Andrey V
AV
Department of Cardiology, Karolinska Hospital, Stockholm, Sweden. agourine@hotmail.com
Bulhak
Aliaksandr A
AA
Gonon
Adrian T
AT
Pernow
John
J
Sjöquist
Per-Ove
PO
D000818:Animals; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D006439:Hemodynamics / Q000187:drug effects; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000517:prevention & control*; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D010396:Penicillamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D009195:Peroxidase / Q000187:drug effects / Q000378:metabolism; D013552:Swine
D002316:Cardiotonic Agents; D020030:Nitric Oxide Donors; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D009195:Peroxidase; D010396:Penicillamine