Clinicopathologic Effects of a 21‐Aminosteroid Compound (U74389G) and High‐Dose Methylprednisolone on Spinal Cord Function After Simulated Spinal Cord Trauma

Abstract

A model simulating acute-compressive spinal cord trauma at the second lumbar spinal cord segment (100 g, 300 seconds) was used to evaluate the efficacy of a vehicle control, methylprednisolone sodium succinate (MPSS), and a 21-aminosteroid compound (U74389G). Dogs were allocated into one of five treatment groups (A to E) using ultrasonographic determination of spinal cord diameters to ensure even distribution of spinal cord diameters among the treatment groups. Initial dosages of the vehicle control (A), methylprednisolone (30 mg/kg of body weight) (B), or U74389G (30 mg/kg, 3 mg/kg, or 10 mg/kg of body weight) (C, D, or E, respectively) were administered intravenously 30 minutes after trauma. Dosages were reduced by one-half for 2 and 6 hour treatments. Then every 4 hours for 42 hours, dosages were reduced one-third and one-sixth from the original dose of methylprednisolone and U74389G, respectively. Neurological examinations were performed daily for 21 days. Histopathological examination of the traumatized spinal cord showed malacic and degenerative lesions. Although significant differences in some portions of the neurological and histopathologic examinations were observed, clinical efficacy for MPSS and U74389G could not be established in this model.

A Preliminary Study of Intravenous Surfactants in Paraplegic Dogs: Polymer Therapy in Canine Clinical SCI

“…Thus, we cannot separate possible interactions between these intravenous agents in this study, only suggesting we did not detect any unacceptable responses to dual administration. The benefits versus the risks of MPSS is now controversial in both fields of medicine (Borgens, 2003;Coates et al, 1995;Pointillart et al, 2000;Short et al, 2000). We think it possible that intravenous PEG administration may replace the use of MPSS as a "standard of care" in the acute phase of the injury if continued clinical testing supports its safety record (Working et al, 1997) and provides further data indicating a benefit to the patient.…”

Fármacos utilizados no tratamento das afecções neurológicas de cães e gatos

“…O tirilazade é um 21-aminoesteróide desenvolvido para uso clinico (BERGMAN;LANZ;SHELL, 2000). Porém em pesquisa, onde o aminocorticosteróide U74389G foi usado na dosagem de 30, 15, 10, 5 e 1,5 mg/kg IV, não foi observado melhora na recuperação neurológica dos animais, quando comparados ao grupo controle (COATES et al, 1995). Isto sustenta a idéia de que os benefícios obtidos com o uso do tirilazade não são comparados com os observados com a administração de succinato sódico de metilprednisolona (SILVEIRA, 2006).…”

“…Estudos de microscopia eletrônica indicam que o DMSO, administrado uma hora após a lesão contusiva em cães, protegeu a bainha de mielina e axônios, reduzindo o edema e acelerando o retorno à função motora (BERGMAN;LANZ;SHELL, 2000). No entanto, em outro estudo realizado com gatos submetidos a trauma medular agudo, não se observou diferença significativa da eficácia do DMSO entre os grupos de animais tratados e não tratados (COATES et al, 1995). A dose recomendada no tratamento do edema ou traumatismo do SNC é de 0,5-1g/kg, IV, q24h, lentamente com solução a 10% (MCDONALD; LANGSTON, 1997).…”

Pharmacological Neuroprotective Therapy for Acute Spinal Cord Injury: State of the Art

“…In spite of these results, a strong controversy exists regarding the beneficial effect of this drug [94][95][96][97]. It has been reported that MP therapy is associated with a 2.6-fold increase in the incidence of pneumonia [98].…”