Pentoxifylline reduces coronary leukocyte accumulation early in reperfusion after cold ischemia.
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 degrees 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.
Gale
S C
SC
Section of Cardiovascular and Thoracic Surgery and the Sarver Heart Center, Tucson, Arizona, USA.
Hokama
J Y
JY
Ritter
L S
LS
Gorman
G D
GD
Copeland
J G
JG
McDonagh
P F
PF
D000818:Animals; D002314:Cardioplegic Solutions / Q000494:pharmacology; D003331:Coronary Vessels / Q000166:cytology; D004195:Disease Models, Animal; D006324:Heart Arrest, Induced / Q000379:methods*; D007964:Leukocytosis / Q000517:prevention & control*; D008297:Male; D015425:Myocardial Reperfusion / Q000009:adverse effects; D010431:Pentoxifylline / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D015427:Reperfusion Injury / Q000517:prevention & control*; D012680:Sensitivity and Specificity; D013997:Time Factors
D002314:Cardioplegic Solutions; D010431:Pentoxifylline