Cardiac-derived neutrophil chemotactic factors: detection in coronary sinus effluents of patients undergoing myocardial revascularization.

Recent studies from our laboratory have demonstrated the release of neutrophil chemotactic factors from isolated rabbit hearts perfused with cardioplegic solutions and from ischemic dog hearts after coronary artery occlusion for 1 hour. On the basis of these animal studies, a test is now made of the hypothesis that neutrophil chemotactic factors are released by myocardial tissues of patients who undergo surgical myocardial revascularization. By means of modified Boyden chambers, the levels of neutrophil chemotactic factors were measured in effluent collected from the coronary sinuses of six patients undergoing cardiopulmonary bypass during periods of cold cardioplegia. Plain cardioplegic solutions were also analyzed. The standard formyl-methionyl-leucyl-phenylalanine, a stimulant of neutrophil recruitment, was used as a positive control solution. Results indicated the recovery of significantly high levels of neutrophil chemotactic factors in patient samples (i.e., 128% +/- 19% of formyl-methionyl-leucyl-phenylalanine) compared with control plain cardioplegic solution (less than 5% of formyl-methionyl-leucyl-phenylalanine) (p less than 0.0001). A standard checkerboard analysis indicated that the observed activity is chemotactic (i.e., directed migration) and not chemokinetic (i.e., random migration). This study also showed that these factors are proteins of a molecular weight in excess of 300 kd and exhibit in vivo activity by recruiting neutrophils into rabbit skin. The absence of immune cell-derived chemoattractants such as interleukin-1 and leukotriene B4 in these coronary sinus effluents suggests that the observed chemotactic activity is cardiac derived. Results of this investigation therefore demonstrate the release of neutrophil chemotactic factors by ischemic human hearts during cardiopulmonary bypass.