STIMULATED LEUKOCYTE ADHESION IN CORONARY MICROCIRCULATION IS REDUCEDBY A CALCIUM-ANTAGONIST

The first step in the acute myocardial inflammatory response is leukoc yte sequestration in the coronary microcirculation. To determine the l ocation(s) of stimulated leukocyte deposition in the coronary microcir culation and the effects of the calcium antagonist, nisoldipine, on le ukocyte adhesion, leukocytes were stimulated with the chemotactic pept ide, N-formylmethionyl-leucyl-phenylalanine (FMLP) and blood cell adhe rence was evaluated using two methods. In vitro leukostasis was evalua ted by measuring the extraction of white cells in nylon fiber columns. We found that diluted whole blood (DWB) demonstrated 30% granulocyte adherence. The chemotactic peptide FMLP (1 muM) significantly increase d adherence to 69%. Pretreatment of the blood with nisoldipine (1 muM) immediately before FMLP significantly reduced the FMLP-induced adhesi on to 47%. In the coronary microcirculation, FMLP caused a marked incr ease in leukocyte sequestration, primarily in coronary capillaries. Th e FMLP effect was somewhat transient because the washout of trapped wh ite cells was similar in the vehicle and FMLP groups. Nisoldipine sign ificantly reduced the FMLP-induced leukostasis in coronary capillaries (P < 0.05). The magnitude of the attenuation of leukostasis with niso ldipine was remarkably similar in both models, suggesting a direct eff ect of this agent on the blood rather than on the blood vessels. These findings offer another possible mechanism by which dihydropyridine ca lcium antagonists may be cardioprotective under pathophysiological con ditions.