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Ann Thorac Surg 2001;71:1305-1311
© 2001 The Society of Thoracic Surgeons

Original article: cardiovascular

Pentoxifylline reduces coronary leukocyte accumulation early in reperfusion after cold ischemia

Stephen C. Gale, MDa,b, Jason Y. Hokama, PhDa,b, Leslie S. Ritter, PhDa,b, Grace D. Gorman, BSa,b, Jack G. Copeland, MDa,b, Paul F. McDonagh, PhDa,b

a Section of Cardiovascular and Thoracic Surgery, University of Arizona Health Sciences Center, Tucson, Arizona, USA
b Sarver Heart Center, University of Arizona Health Sciences Center, Tucson, Arizona, USA

Accepted for publication November 21, 2000.

Address reprint requests to Dr McDonagh, Department of Cardiothoracic Surgery, University of Arizona Health Sciences Center, PO Box 245071, 1501 N Campbell, Tucson, Arizona 85724
e-mail: pmcdonag{at}u.arizona.edu

Background. Ischemia/reperfusion injury can complicate recovery in cardiac operations. Ischemia induces endothelial dysfunction, which may contribute to leukocyte accumulation during reperfusion. Leukocyte-mediated injury may then occur. Using intravital microscopy we previously reported increased leukocyte retention in coronary capillaries and venules during early reperfusion during warm ischemia/reperfusion. In this study we investigated whether cold cardioplegic protection would limit leukocyte sequestration in coronary microvessels early in reperfusion. Pentoxifylline (PTX) has antiinflammatory effects and may limit endothelial dysfunction during ischemia/reperfusion. The effect of cardioplegia modification with PTX was also examined.

Methods. Isolated rat hearts were subjected to 90 minutes of 4°C ischemia after arrest with cardioplegia. Hearts were reperfused with diluted whole blood containing fluorescent-labeled leukocytes. Leukocyte retention in coronary microvessels was observed with intravital microscopy. Three groups were studied, nonischemic control, cold ischemia, and PTX-modified cold ischemia.

Results. In coronary capillaries, leukocyte trapping was nearly doubled in unmodified cold ischemia versus control. PTX modification significantly reduced leukocyte accumulation. In coronary venules, greater leukocyte adhesion was observed in unmodified cold ischemia compared to nonischemic controls. PTX modification significantly reduced leukocyte adhesion.

Conclusions. Cold cardioplegia did not prevent leukocyte retention in the coronary microcirculation early in reperfusion. PTX modification of cardioplegia significantly reduced leukocyte sequestration in coronary capillaries and venules. Preserving endothelial function during ischemia may limit leukocyte accumulation and ischemia/reperfusion injury after cardiac operation.




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