Effects of oral Stanazolol administration on Tracheal Collapse of dog

Title: STANOZOLOL USE IN TRACHEAL COLLAPSE THERAPY Objectives: Tracheal collapse (CT) is a respiratory insufficiency syndrome most common in toy and miniature dog breeds. It is characterized by a typical chronic cough, dispnea and tachypnea. The progressive worsening of the disease leads to hypoxia and episodical syncopes. Little is known about the causes of tracheal collapse, even if a multifactorial aetiology was identified. A recent pathogenetic hypothesis points the dystrophy of the cartilage rings and of the tracheal dorsal fibro-muscular structures as a possible cause of the disease.. The aim of this study was to evaluate the therapeutic benefits of a chronic daily administration of low doses of Stanozolol an androgen of synthesis with anti-dystrophic action in subjects with different tracheal collapse gravity. Materials and Methods A total of 13 toy breed dogs affected by tracheal collapse were admitted to our clinic. The diagnosis of CT the was based on 1) relevant historical data 2) clinical findings 3) thoracic radiographs. Complete blood count and plasma biochemical profile were performed to evaluate the general health status and the presence of possible pre-admission exclusion criteria (cardiovascular diseases, hepatobiliary diseases, renal failure, pregnancy, current pharmacological therapies). According to Tangner and Hobson classification (1982) we identified for all animals the degree class of TC and we establish a correlate clinical score (CS). Stanozolol (Stargate ® cpr, ACME®, Italy) 0.3 mg/Kg was administered orally once a day for two months. Dogs were examined at day 0 and at day 60. The main parameter considered was the changes in CS during therapy. Statistical analisys of outcomes was performed by the non parametric by Wilcoxon matched-pairs signed-ranks test and by the Sign test. P< 0.05 was considered significant. Results The treatment elicited an improvement of CS in all the animals, with a complete recovery in 8 out of 13 dogs. In particular, the resulted series of paired values of CS and the respective improvement degree for each dog were: 1*(3**, 0**)=+3****; 2(3,1)=+2; 3(3,1)=+2; 4(1,0)=+1; 5(1,0)=+1; 6(1,0)=+1; 72,0)=+2; 9(2,0)=+2; 10(3,1)=+2; 11(3,2)=+1; 12(1,0)=+1; 13(1,0)=+1 {*=dog identification number; **= Clinical Score at day 0; ***= Clinical Score at day 60; ****= degree improvement}. Statistical analysis score comparing values before and after treatment. No alterations of hepatic function and of the sexual secondary characters were found. Conclusion: Our results underline a significant reduction of the clinical scores in response to Stanozolol therapy. Stanozolol is a synthetic androgen derived from testosterone; however Stanozolol shows a higher affinity for the glucocorticoid receptors than for those of the androgens. The glucocorticoid receptor block is carried out for low Stanozolol doses and it reduces the tissue catabolic activity glucocorticoid mediated. In vitro studies show a clear positive effect of Stanozolol on collagen synthesis in fibroblastic cell cultures: this action is mediated by an increase in the synthesis of the cytokine TGFß-1. In particular, TGFß-1 is involved in the proliferation of chondrocytes and in the apposition of extracellular matrix. We may hypothesize that the benefic action of Stanozolol in the CT therapy induces an increase in TGFß-1 synthesis by tracheal chondrocytes and fibroblasts.