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Cardiovascular Research 1993 27(3):377-383; doi:10.1093/cvr/27.3.377
© 1993 by European Society of Cardiology
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Copyright © 1993, European Society of Cardiology

Transcardiac alteration of neutrophil function relates to myocardial ischaemia/reperfusion injury

Shiro Hoshida, Tsunehiko Kuzuya, Hisakazu Fuji, Hiroshi Oe, Masatsugu Hori, Takenobu Kamada and Michihiko Tada

Osaka University School of Medicine, 1-1-50 Fukushima, Fukushima-ku, Osaka 553, Japan – Division of Cardiology, First Department of Medicine: S Hoshida, H Fuji, H Oe, M Hori, T Kamada; Department of Pathophysiology: T Kuzuya, M Tada.

Correspondence to Dr Hishida.

Objective: The aim was to define the relation between transcardiac changes in neutrophil function in myocardial ischaemia and the progression of myocardial necrosis. Methods: Samples of blood from carotid artery, jugular vein, and cardiac vein streaming from the ischaemic area were taken simultaneously in a canine coronary occlusion-reperfusion model of myocardial infarction. Neutrophil function was evaluated by neutrophil count, whole blood chemiluminescence and leucocyte infiltration into the ischaemic myocardium. Myocardial necrosis was assessed by plasma creatine kinase and dual staining technique using Evans blue dye and triphenyltetrazolium chloride. Effects of a free radical scavenger, N-2-mercaptopropionyl glycine (MPG), initiated 15 min before reperfusion and continued during the reperfusion phase, were also examined. Results: Whole blood chemiluminescence of the cardiac vein was reduced at 90 min after coronary artery occlusion as compared to carotid artery [5.8(SEM 0.5) v 7.5(0.7) count·103 cell neutrophil–1·10 min–1, p<0.05], and then increased abruptly after reperfusion to peak after 10 min of reperfusion [7.1(0.7) count·103 cell neutrophil–1·10 min–1]. The neutrophil count in cardiac venous blood was significantly reduced within 5 min of reperfusion. MPG significantly attenuated the reperfusion associated increase in cardiac vein whole blood chemiluminescence and the decrease in the cardiac venous blood neutrophil count. The increase in myocardial free radical generation 1-3 h after reperfusion, as assessed by the electron paramagnetic resonance spin trapping technique, was reduced markedly, as was the extent of leucocyte infiltration into the ischaemic myocardium. Under these conditions, administration of MPG significantly reduced myocardial infarct size [40.3(4.5)% v 21.4(4.2)%, p<0.05]. A marked increase in transcardiac creatine kinase release after reperfusion observed in control dogs was also reduced significantly. Conclusions: A transient alteration of neutrophil function occurs in the coronary circulation immediately after reperfusion, which may augment neutrophil infiltration and free radical generation in the ischaemic myocardium, leading to the propagation of myocardial ischaemia/reperfusion injury.

Cardiovascular Research 1993;27:377-383

KEYWORDS whole blood chemiluminescence; electron paramagnetic resonance spectroscopy; leucocyte infiltration; N-2-mercaptopropionyl glycine

This study was supported in part by grants from the Minister of Education, Science and Culture, and of Health and Welfare, Japan.


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