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From the Department of Physiology, Jefferson Medical College, Thomas
Jefferson University, Philadelphia, Pa. Dr DJ Lefer is now at the Department
of Physiology, Louisiana State University School of Medicine, Shreveport, La.
Correspondence to Dr Allan M. Lefer, Department of Physiology, Jefferson Medical College, 1020 Locust St, Philadelphia, PA 19107. E-mail lefer1{at}jeflin.tju.edu
Background—Neutrophils (PMNs) are
known to contribute to both cardiac dysfunction and myocardial necrosis
after reperfusion of an ischemic heart. Moreover, platelets
are also important blood cells that can aggravate myocardial
ischemic injury. This study was designed to test the effects of
PMNs and platelets separately and together in provoking cardiac
dysfunction in isolated perfused rat hearts after ischemia
and reperfusion.
Methods and Results—Control rat hearts not subjected to
ischemia were perfused without blood cells for 80 minutes.
Additional control rat hearts were perfused with 75x106
PMNs, with 100x106 platelets, or with
75x106 PMNs+100x106 platelets over a
5-minute perfusion followed by a 75-minute observation period. No
significant reduction in coronary flow, left
ventricular developed pressure (LVDP), or the first
derivative of LVDP (dP/dtmax) was observed at the end of
the observation period in any nonischemic group. Similarly,
global ischemia (I) for 20 minutes followed by 45 minutes of
reperfusion (R) produced no sustained effects on the final recovery of
any of these parameters in any group of hearts perfused in
the absence of blood cells. However, I/R hearts perfused with either
PMNs or platelets alone exhibited decreases in these variables
of 10% to 12% (P<0.05 from control). Furthermore, I/R
hearts perfused with both PMNs and platelets exhibited decreases of
50% to 60% in all measurements of cardiac function
(P<0.001). These dual-cell–perfused I/R hearts also
exhibited marked increases in cardiac myeloperoxidase (MPO) activity,
indicating a significant PMN infiltration, and enhanced P-selectin
expression on the coronary microvascular
endothelium. All cardiodynamic effects as well as MPO
accumulation and PMN infiltration were markedly attenuated by a sialyl
LewisX-oligosaccharide or a recombinant soluble
P-selectin ligand, which inhibits selectin-mediated cell adhesion.
Conclusions—These results provide evidence that platelets and
neutrophils act synergistically in provoking postreperfusion cardiac
dysfunction and that this may be largely due to cell-to-cell
interactions mediated by P-selectin. These findings may help explain
the reperfusion injury phenomenon.
© 1998 American Heart Association, Inc.
Basic Science Reports
Synergism Between Platelets and Neutrophils in Provoking Cardiac Dysfunction After Ischemia and Reperfusion
Role of Selectins
Key Words: myocardium • cell adhesion molecules • contractility • selectins
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