Isoflurane prevents platelets from enhancing neutrophil-induced coronary endothelial dysfunction

We evaluated whether platelets can enhance polymorphonuclear neutrophil-induced coronary endothelial dysfunction, and, after observing this, whether isoflurane can prevent the effect. Neutrophils, coronary artery segments, and platelets were obtained from 25 healthy dogs. Coronary artery rings were exposed to neutrophils activated with platelet-activating factor (1.0 microM), and after washing and preconstriction with U46619, were evaluated for concentration-related responses to acetylcholine, an endothelium-dependent vasorelaxing drug. Superoxide production by activated neutrophils was measured spectrophotometrically. Adherence of the activated neutrophils to the endothelium of coronary segments was assessed by direct counting of neutrophils labeled with fluorescent dye. Measurements were performed in absence and presence of isoflurane (1 minimum alveolar concentration) both with and without platelets. The presence of platelets enhanced the neutrophil-induced rightward shift in the concentration-vasorelaxation response curve to acetylcholine (the concentration of acetylcholine required to elicit 50% of maximal relaxation (-log M) was increased from 6.78 +/- 0.7 to 5.26 +/- 0.6), and it increased superoxide oxide production from 45.0 +/- 4.2 to 54.3 +/- 4.2 nM O2-/5 x 10(6) neutrophils and adherence of activated neutrophils from 204 +/- 10 to 268 +/- 5 neutrophils/mm2. Isoflurane abolished these effects of platelets. In conclusion, platelets enhanced the ability of neutrophils to cause coronary endothelial dysfunction. This effect was prevented by isoflurane. This may be attributable to an inhibitory action on superoxide production by the neutrophils leading to reduced expression of endothelial adhesion molecules and, in turn, reduced neutrophil adherence.