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Deleterious Effects of Intra-arterial Administration of Particulate Steroids on Microvascular Perfusion in a Mouse
Elisabeth Laemmel1, Nicolas Segal1, Massoud Mirshahi1
1From 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.).
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.
Insights
Certain particulate steroids rapidly halt blood flow by causing red blood cells (RBCs) to aggregate and change shape. This significantly impacts microvascular perfusion, unlike other tested steroids.
Area of Science:
- Pharmacology
- Microcirculation Research
- Hematology
Background:
- Particulate steroids are utilized for their localized effects.
- Understanding their impact on microvascular perfusion is crucial for clinical application.
- Interactions with red blood cells (RBCs) may influence their hemodynamic effects.
Purpose of the Study:
- To evaluate the in vivo effects of particulate steroids on microvascular perfusion in mice.
- To investigate the in vitro interactions between particulate steroids and human RBCs.
Main Methods:
- Intravital microscopy of mouse cremaster muscle to assess in vivo microvascular perfusion.
- In vitro blood microcinematography and electron microscopy to study steroid-RBC interactions.
- Comparison of saline, dexamethasone, cortivazol, methylprednisolone, triamcinolone, and prednisolone treatments.
Main Results:
- Prednisolone, methylprednisolone, and triamcinolone caused rapid cessation of blood flow in arterioles and venules.
- Functional capillary density significantly decreased with methylprednisolone, triamcinolone, and prednisolone.
- RBC aggregation and transformation into spiculated RBCs were observed in vitro and correlated with in vivo findings.
- Cortivazol and dexamethasone showed limited effects on microvascular perfusion.
Conclusions:
- Particulate steroids like prednisolone, methylprednisolone, and triamcinolone can cause immediate and severe disruption of microvascular perfusion.
- RBC aggregation and morphological changes are the primary mechanisms behind this effect.
- Non-particulate steroids or certain particulate steroids (e.g., cortivazol) do not exhibit these adverse hemodynamic effects.
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