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Ann Thorac Surg 1998;66:2072
© 1998 The Society of Thoracic Surgeons

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Invited Commentary

^a Department of Cardiovascular Surgery, Osaka Medical Center and Research Institute for Maternal and Child Health, 840 Murodo-cho, Izumi, Osaka 594-1101, Japan

Invited commentary

Ritter and colleagues examined the effect of fucoidin to the leukocyte accumulation in the coronary capillaries and venules during the early period of reperfusion after ischemia. They could visualize the coronary microcirculation directly with a fluorescence microscope and could present a direct evidence that the antiadhesion treatment did prevent leukocyte accumulation.

Although the findings are very important and can provide additional information to the role of adhesion molecules in reperfusion injury, I have some concerns about this study.

Ritter and coworkers demonstrated the inhibition of leukocyte accumulation by fucoidin, but they could not show any cardioprotective effect by this treatment. The perfusate during reperfusion contained high concentration of potassium (30 mmol/L) because static microscopic field was necessary for this experiment. High concentration of potassium could alter the basic coronary vascular tone and the inhibition of leukocyte accumulation by fucoidin might not show the reduction in coronary vascular resistance. I hope they will duplicate these experiments but next time use perfusate of normal potassium concentration and assess the coronary vascular resistance and ventricular function. The other possible explanation for the negative findings of the cardioprotective effect may be the dose of fucoidin. The 50% effective dose of fucoidin to block leukocyte rolling was 2.1 mg/L in the studies by Rochon and associates [1] and 2.5 mg/L by Ley and associates [2]. The dose of fucoidin Ritter and colleagues used (0.36 mg/mLl = 360 mg/L) was considerably higher than the doses reported previously [3]. They should show that the higher concentration of fucoidin would have no deleterious effect on coronary vasculature or the myocardium.

They speculate the inhibition of both P-selectin and L-selectin might be responsible for this antiadhesion therapy. L-selectin was constitutively expressed on the surface of leukocytes and was easily shed soon after the activation of the leukocytes. I assume that L-selectin on the leukocytes in this experimental setting was already shed before the infusion to the coronary artery because the leukocytes had been activated during the process to make diluted whole blood. Therefore, the L-selectin-mediated leukocyte adhesion might not be responsible for the findings in this experiment.

Recent report by Sato and colleagues [4] showed that gradual reperfusion prevents myocardial and endothelial reperfusion injury despite a paradoxical increase of leukocyte accumulation. And this study by Ritter and coworkers could not present a cardioprotective effect despite of the prevention of leukocyte accumulation. These interesting findings and the role of the shedding of L-selectin in reperfusion injury should be the problems to be elucidated in the future.

References

1. Rochon Y.P., Simon S.I., Lynam E.B., Sklar L.A. A role for lectin interactions during human neutrophil aggregation. J Immunol 1994;152:1385-1393.[Abstract]
2. Ley K., Linnemann G., Meinen M., Stoolman L.M., Gaehtgens P. Fucoidin, but not yeast polyphosphomannan PPME, inhibits leukocyte rolling in venules of the rat mesentery. Blood 1993;81:177-185.[Abstract/Free Full Text]
3. Miura T., Nelson D.P., Schermerhorn M.L., et al. Blockade of selectin-mediated leukocyte adhesion improves postischemic function in lamb heart. Ann Thorac Surg 1996;62:1295-1300.[Abstract/Free Full Text]
4. Sato H., Jordan J.E., Zhao Z.Q., Sarvotham S.S., Vinten-Johansen J. Gradual reperfusion reduces infarct size and endothelial injury but augments neutrophil accumulation. Ann Thorac Surg 1997;64:1099-1107.[Abstract/Free Full Text]

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