Neutrophil inhibition contributes to cardioprotection by postconditioning

• Published in: Acta anaesthesiologica Scandinavica Vol. 56; no. 1; pp. 48 - 56
• Main Authors: GRANFELDT, A., JIANG, R., WANG, N.-P., MYKYTENKO, J., ELDAIF, S., DENEVE, J., ZHAO, Z.-Q., GUYTON, R. A., TØNNESEN, E., VINTEN-JOHANSEN, J.
• Format: Journal Article
• Language: English
• Published: Oxford Blackwell Publishing Ltd 01.01.2012; Blackwell
• Subjects: Anesthesia; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Biological and medical sciences; Blood; Blood Pressure - drug effects; Blood Pressure - physiology; Chemiluminescence; coronary artery; Creatine Kinase - blood; Data processing; Dogs; Heart Rate - drug effects; Heart Rate - physiology; Immunohistochemistry; Ischemic Postconditioning - methods; Leukocytes (neutrophilic); Luminescence; Luminol; Male; Medical sciences; Myocardial Infarction - pathology; Myocardial Infarction - prevention & control; Myocardial Reperfusion Injury - pathology; Myocardial Reperfusion Injury - prevention & control; Myocardium - pathology; Necrosis; Neutrophils - drug effects; Occlusion; Oxygen Consumption - drug effects; Rats; Rats, Sprague-Dawley; Reperfusion; Superoxide; Superoxides - metabolism; Veins; Anesthesia; Cardioprotective agent; Neutrophil
• ISSN: 0001-5172; 1399-6576
• DOI: 10.1111/j.1399-6576.2011.02577.x

Background Postconditioning (postcon) reduces infarct size, myocardial superoxide (•O2) generation, and neutrophil (PMN) accumulation. It is unknown whether inhibition of PMNs influence cardioprotection by postcon. The present study tested the following hypotheses: (1) myocardial salvage by postcon is modified by inhibition of PMNs and (2) postcon directly inhibits PMN •O2 generation. Methods For hypothesis 1, a deductive approach was used to determine infarct size in vivo with and without PMNs in rats, and for hypothesis 2, blood sampled from the anterior interventricular vein (AIV) in a canine model was used. Protocol 1: anesthetized rats, subjected to 30 min of coronary artery occlusion and 3 h of reperfusion, were randomized to control (n = 13), postcon (n = 13), PMN‐depletion: (n = 9), and postcon in PMN‐depleted rats (n = 9). Protocol 2: blood was sampled at baseline, 2 h and 24 h from the AIV, draining the area at risk (AAR) in anesthetized dogs with 60 min coronary occlusion ± postcon; whole blood was analyzed for •O2 by luminol‐enhanced chemiluminescence. Results Postcon and PMN depletion reduced infarct size (42.6 ± 2.1%, P < 0.05 vs. control, and 43.9 ± 3.0%, P < 0.05 vs. control, respectively) vs. control (58.8 ± 0.9%), with no further decrease with postcon in PMN‐depleted rats (37.2 ± 2.9%, P = 0.34 vs. postcon). PMN accumulation in AAR was less in postcon (21.2 ± 0.3%, P < 0.05 vs. control) and PMN‐depleted (9.4 ± 0.3%, P < 0.05 vs. control) vs. control (30.5 ± 1.2%), with a further decrease in the postcon + PMN depletion group (5.4 ± 0.6%, P < 0.05 vs. control). In dogs, •O2 release by PMNs increased at 2 h and 24 h of R, which was reduced to baseline levels by postcon. Conclusions These data imply PMN involvement in cardioprotection by postconditioning.