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Transcardiac alteration of neutrophil function relates to myocardial ischaemia/reperfusion injury
1First Department of Medicine, Osaka University School of Medicine, Japan.
Insights
Myocardial ischemia triggers changes in neutrophil function, increasing damage after reperfusion. A free radical scavenger, N-2-mercaptopropionyl glycine (MPG), reduced this injury and infarct size in a canine model.
Area of Science:
- Cardiovascular Research
- Inflammation and Immunology
- Myocardial Infarction Pathophysiology
Background:
- Myocardial ischemia and reperfusion (I/R) injury are critical complications following acute myocardial infarction.
- Neutrophil activation and infiltration play a significant role in the progression of myocardial necrosis during I/R.
- Understanding the dynamics of neutrophil function in the coronary circulation is crucial for developing effective therapeutic strategies.
Purpose of the Study:
- To elucidate the relationship between transcardiac neutrophil function alterations and myocardial necrosis progression during ischemia.
- To investigate the impact of reperfusion on neutrophil behavior in the ischemic myocardium.
- To evaluate the efficacy of a free radical scavenger, N-2-mercaptopropionyl glycine (MPG), in mitigating I/R injury.
Main Methods:
- A canine coronary occlusion-reperfusion model was employed to simulate myocardial infarction.
- Simultaneous blood sampling from carotid artery, cardiac vein, and jugular vein to assess neutrophil count and function (chemiluminescence).
- Myocardial necrosis was quantified using plasma creatine kinase levels and dual staining; MPG's effects were examined.
Main Results:
- Cardiac venous chemiluminescence and neutrophil count showed significant alterations during ischemia and reperfusion.
- MPG administration attenuated the reperfusion-induced increase in neutrophil activity and reduced myocardial free radical generation.
- MPG treatment significantly decreased myocardial infarct size and creatine kinase release, indicating reduced necrosis.
Conclusions:
- Transient changes in neutrophil function within the coronary circulation post-reperfusion exacerbate myocardial I/R injury.
- Neutrophil infiltration and free radical generation contribute to the propagation of ischemic damage.
- MPG demonstrates a protective effect against myocardial I/R injury by modulating neutrophil function and oxidative stress.
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 x 10(3) cell neutrophil-1 x 10 min-1, p < 0.05], and then increased abruptly after reperfusion to peak after 10 min of reperfusion [7.1(0.7) count x 10(3) cell neutrophil-1 x 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.