Nicorandil attenuates reperfusion injury after long cardioplegic arrest.
The cardioprotective efficacy of nicorandil in cardiac surgery was determined using a surgically relevant 4-hr cardioplegic arrest model. Each isolated rabbit heart was parabiotically blood-perfused using a modified Langendorff column. The magnitude of left ventricular developed pressure and rate of change of developed pressure over time were measured before (baseline) and after ischemia. Nicorandil was administered either pre-ischemia, post-ischemia, pre/post-ischemia, or continuously (before, during, and after ischemia). The endothelium of the coronary artery was observed by scanning electron microscopy. Serum myeloperoxidase activities were also measured. Although pretreatment with nicorandil did not affect recovery of developed pressure, administration of nicorandil after ischemia, or before and after ischemia, enhanced the recovery of developed pressure. Serum myeloperoxidase activity was decreased in the pre/post-ischemia and continuous groups. Endothelial reperfusion injury decreased in all nicorandil-treated groups. Administration of nicorandil attenuated ischemia-reperfusion injury of the myocardium and coronary endothelium while ameliorating leukocyte activation. In the event of unexpected prolonged cardioplegic arrest, administration of nicorandil, even just after declamping, may improve cardiac function. However, pre-ischemia administration alone was not helpful in the heart subjected to prolonged cardioplegic arrest.
Takarabe
Kyoumi
K
Department of Thoracic and Cardiovascular Surgery, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan.
Okazaki
Yukio
Y
Higuchi
Shinya
S
Murayama
Junichi
J
Natsuaki
Masafumi
M
Itoh
Tsuyoshi
T
D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000473:pathology; D005112:Extracorporeal Circulation; D006324:Heart Arrest, Induced / Q000009:adverse effects*; D007962:Leukocytes / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control / Q000628:therapy*; D020108:Nicorandil / Q000494:pharmacology* / Q000627:therapeutic use; D009195:Peroxidase / Q000097:blood; D011817:Rabbits; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D017725:Ventricular Pressure / Q000187:drug effects
D002316:Cardiotonic Agents; D020108:Nicorandil; D009195:Peroxidase