title: Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse Model.
abstract: Purpose To determine the in vivo effects of several particulate steroids on microvascular perfusion by using intravital microscopy in a mice model and to investigate the in vitro interactions between these particulate steroids and red blood cells (RBCs). Materials and Methods The study was conducted in agreement with the guidelines of the National Committee of Ethic Reflection on Animal Experimentation. By using intravital microscopy of mouse cremaster muscle, the in vivo effects of several particulate steroids on microvascular perfusion were assessed. Four to five mice were allocated to each of the following treatment groups: saline solution, dexamethasone sodium phosphate, a nonparticulate steroid, and the particulate steroids cortivazol, methylprednisolone, triamcinolone, and prednisolone. By using in vitro blood microcinematography and electron microscopy, the interactions between these steroids and human RBCs were studied. All results were analyzed by using nonparametric tests. Results With prednisolone, methylprednisolone, or triamcinolone, blood flow was rapidly and completely stopped in all the arterioles and venules (median RBC velocity in first-order arterioles, 5 minutes after administration was zero for these three groups) compared with a limited effect in mice treated with saline, dexamethasone, and cortivazol (20.3, 21.3, and 27.5 mm/sec, respectively; P < .003). This effect was associated with a large decrease in the functional capillary density (4.21, 0, and 0 capillaries per millimeter for methylprednisolone, triamcinolone, or prednisolone, respectively, vs 21.0, 21.4, and 19.1 capillaries per millimeter in mice treated with saline, dexamethasone, and cortivazol, respectively; P < .003). This was because of the rapid formation of RBC aggregates. However, no change in microvascular perfusion was associated with administration of cortivazol or dexamethasone. In vitro experiments confirmed the formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs with the same steroids. Conclusion Several particulate steroids have an immediate and massive effect on microvascular perfusion because of formation of RBC aggregates associated with the transformation of RBCs into spiculated RBCs. (©) RSNA, 2016 Online supplemental material is available for this article.
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Laemmel
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Nicolas
authors.initials: N
authors.lastname: Segal
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Massoud
authors.initials: M
authors.lastname: Mirshahi
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Dalel
authors.initials: D
authors.lastname: Azzazene
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Sylvie
authors.initials: S
authors.lastname: Le Marchand
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Marc
authors.initials: M
authors.lastname: Wybier
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Eric
authors.initials: E
authors.lastname: Vicaut
authors.affiliation: From the Laboratoire Etude de la Microcirculation, Université Denis-Diderot Paris 7, Paris, France (E.L., N.S., E.V.); Hôpital Lariboisière, Assistance Publique des Hôpitaux de Paris and Université Paris Diderot, Sorbonne, Paris, France (M.M., D.A., S.L.M.); and Service de Radiologie Ostéo-articulaire, Hôpital Lariboisière, 2 Rue Ambroise Paré, 75010 Paris, France (M.W., J.D.L.).
authors.forename: Jean-Denis
authors.initials: JD
authors.lastname: Laredo
mesh_terms: D000818:Animals; D062186:Arterial Pressure; D007269:Injections, Intra-Arterial / Q000009:adverse effects; D000069416:Intravital Microscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008833:Microcirculation / Q000187:drug effects; D008854:Microscopy, Electron; D046529:Microscopy, Electron, Transmission; D052638:Particulate Matter / Q000009:adverse effects; D013256:Steroids / Q000008:administration & dosage* / Q000009:adverse effects*
chemical_list: D052638:Particulate Matter; D013256:Steroids