Question: 

The pathogenesis of myocardial ischemia-reperfusion injury (MI/R) involves an inflammatory response in the reperfused myocardium. Modulation of this response constitutes a potential target to protect the heart from MI/R. Recently the spleen has been proved an important origin for cells invading the myocardium upon damage. Thus, we applied splenectomy to interfere cell invasion. In an additional pharmacological approach, the sphingosine 1-phosphate (S1P) agonist FTY720 was applied at the onset of reperfusion in order to reduce the number of invading cells.

Methods and Results: 

In a closed chest model of MI/R, infarct size was assessed by TTC staining after 24 h, and hemodynamic parameters were recorded after 24 h and 21 days by catherization using a Millar catheter in splenectomised versus sham operated animals, animals postconditioned with 1mg*kg^-1 FTY720 i.p. Infarct size, and immune cell invasion of Gr-1^pos and CD45^pos cells were significantly reduced by both splenectomy, and FTY720 treatment. However, in the splenectomised group FTY720 failed to further increase the beneficial effect of splenectomy on myocardial survival. Evaluation after 21 days of reperfusion revealed that splenectomised animals had an improved hemodynamic outcome compared to the control group. Application of FTY720 before reperfusion did also reduce deterioration of cardiac function after MI/R.

Conclusion: 

Both, splenectomy and FTY720 treatment lowered the number of inflammatory cells invading the myocardium after MI/R injury and acted cardioprotectively within the first 21 days. Anti-inflammatory action seems to improve cardiomyocyte survival and cardiac function after MI/R.