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Temporal relation between neutrophil accumulation and myocardial reperfusion injury
E F Smith1, J W Egan, P J Bugelski
1Department of Pharmacology, Smith Kline and French Laboratories, King of Prussia, Pennsylvania 19406.
Abstract:
Infiltration of polymorphonuclear leukocytes (PMN) is associated with the progression of myocardial infarction and reperfusion injury. However, little is known about the time course of cellular infiltration. To investigate this issue, rats were subjected to 30 min of coronary artery occlusion followed by reperfusion for less than or equal to 96 h. Myocardial injury was determined by measuring the depletion of myocardial creatine phosphokinase activity, and PMN infiltration was assessed by measuring myeloperoxidase (MPO) activity. MPO activity increased from 0.7 U/g tissue in non-operated animals, to a peak of 6.7 +/- 0.8 and 6.4 +/- 1.4 U/g at 6 and 24 h after coronary artery reperfusion, respectively. MPO activity decreased to 3.3 +/- 0.8 U/g at 48 h and 1.1 +/- 0.4 U/g at 96 h, suggesting diminished PMN accumulation. Histological examination confirmed the accumulation and resolution of PMN over the 96-h period. At 24 h, there was a significant linear correlation between infarct size and MPO activity, whereas at 96 h no relationship was found. These data indicate that PMN infiltration occurs early in response to reperfusion injury and persists for only 24 h after initiation of reperfusion. These findings suggest that attempts to moderate inflammatory cell responses to myocardial injury should be administered early after coronary artery reperfusion to limit the accumulation of potentially deleterious inflammatory cells.
Insights
Polymorphonuclear leukocyte (PMN) infiltration peaks early after heart reperfusion injury, correlating with damage at 24 hours. Interventions targeting this inflammation should occur soon after reperfusion.
Area of Science:
- Cardiovascular Research
- Inflammation Biology
- Myocardial Infarction Studies
Background:
- Polymorphonuclear leukocytes (PMN) infiltration is linked to myocardial infarction and reperfusion injury progression.
- The precise timing of cellular infiltration in these conditions remains poorly understood.
Purpose of the Study:
- To investigate the time course of polymorphonuclear leukocyte (PMN) infiltration following myocardial reperfusion injury.
- To determine the relationship between PMN infiltration and infarct size over time.
Main Methods:
- Rats underwent 30 minutes of coronary artery occlusion followed by up to 96 hours of reperfusion.
- Myocardial injury was assessed by creatine phosphokinase activity depletion.
- PMN infiltration was quantified using myeloperoxidase (MPO) activity assays and confirmed with histology.
Main Results:
- MPO activity, indicating PMN infiltration, peaked at 6 and 24 hours post-reperfusion (6.7 +/- 0.8 and 6.4 +/- 1.4 U/g, respectively).
- MPO activity significantly decreased by 48 and 96 hours, showing reduced PMN accumulation.
- A strong correlation between infarct size and MPO activity was observed at 24 hours, but not at 96 hours.
Conclusions:
- PMN infiltration occurs early in response to myocardial reperfusion injury, persisting for approximately 24 hours.
- These findings suggest that early administration of anti-inflammatory therapies after reperfusion may be crucial for limiting inflammatory cell-induced damage.