2017 ACVIM Forum Research Abstract Program

There was statistical difference between control and pre-capillary moderate/severe groups (P < 0.05), and from pos-capillary moderate/severe and control groups (P < 0.05) when evaluating TAPSEidx parameter. Results are summarized in Table 1 LASSBio 294 is a compound, developed by the Laboratory of Evaluation and Synthesis of Bioactive Substances (LASSBio Ã’ ) of the Federal University of Rio de Janeiro (UFRJ) made from the substrate safrole, a compound extracted from sassafras oil, found in Brazilians plants such as the cinnamon-white (Ocotea pretiosa). The inodilator effect of the compound has been demonstrated in bioassays, using isolated and intact aortic rings, and in whole hearts and fractions of myocardial of rats, suggesting that the mechanism of action for its vasodilatory effects is related to inhibition of phosphodiesterases, and the inotropic effect on the increased Ca 2 + uptake by the sarcoplasmic reticulum. In rats with experimentally induced myocardial infarction, LASSBio 294 decreased collagen deposition, presumably regulating inflammation mediators. In addition, it increased cardiac lusitropism, decreasing left ventricular filling pressure, modulating the action of the SERCA protein, increasing Ca 2 + uptake by the sarcoplasmic reticulum, inducing myocardial relaxation and improving diastolic function. In previous studies performed by these authors on healthy beagle dogs, the oral administration of the compound lowered blood pressure, without causing hypotension or other toxic effects and increased the shortening fraction by 19.1%. Faced with the need to test the compound in a non-rodent mammal with myocardial disease, it was proposed in this study to verify the action of LASSBio 294 (2 mg/kg, n = 7) on the cardiovascular parameters of New Zealand rabbits with dilated cardiomyopathy induced by doxorubicin, using pimobendan (3 mg/kg, n = 6) as a positive control, both treatments were administered every 12 hours for 30 days. DCM was induced by intravenous administration of 1 mg/kg of doxorubicin, twice a week for three weeks and weekly thereafter until FS = 25% or less was achieved. The animals were evaluated weekly by: electrocardiography, echocardiography, blood pressure measurement, chest X-ray and biomarkers of renal and hepatic function and myocardial injury. This study was approved by the Ethics Committee of Animal Use of the Federal University of Goias (UFG) under the protocol number 006 / 14. The data were submitted to analysis of variance and compared by means of Tukey test, adopting 5% of significance. Under these conditions, LASSBio 294 increased systolic function, increasing FS by 35% in the second week, and improved diastolic function in a superior manner to pimobendan, maintaining the E /A ratio <1 and E '/ A' <1 and reducing IVRT, without altering the arterial pressure or producing proarrhythmogenic or toxic effects and also, reduced the serum concentration of creatinine. However, it did not prevent the evolution of the congestive condition, since two animals presented pulmonary edema and effusions. Thus, the pre-clinical in vitro and in vivo testing stages of LASSBio 294 was concluded, and it was tested in rodent and non-rodent mammals, healthy and with induced DCM, with a positive inodilator and lusitropic effect. Therefore, it can be concluded that LASSBio 294 is a promising compound, which needs to be used in clinical trials with individuals with naturally occurring DCM, so that it can complete the neces