Using cultured canine cardiac slices to model the autophagic flux with doxorubicin.

Chemotherapy-induced impairment of autophagy is implicated in cardiac toxicity induced by anti-cancer drugs. Imperfect translation from rodent models and lack of in vitro models of toxicity has limited investigation of autophagic flux dysregulation, preventing design of novel cardioprotective strategies based on autophagy control. Development of an adult heart tissue culture technique from a translational model will improve investigation of cardiac toxicity. We aimed to optimize a canine cardiac slice culture system for exploration of cancer therapy impact on intact cardiac tissue, creating a translatable model that maintains autophagy in culture and is amenable to autophagy modulation. Canine cardiac tissue slices (350 µm) were generated from left ventricular free wall collected from euthanized client-owned dogs (n = 7) free of cardiovascular disease at the Foster Hospital for Small Animals at Tufts University. Cell viability and apoptosis were quantified with MTT assay and TUNEL staining. Cardiac slices were challenged with doxorubicin and an autophagy activator (rapamycin) or inhibitor (chloroquine). Autophagic flux components (LC3, p62) were quantified by western blot. Cardiac slices retained high cell viability for >7 days in culture and basal levels of autophagic markers remained unchanged. Doxorubicin treatment resulted in perturbation of the autophagic flux and cell death, while rapamycin co-treatment restored normal autophagic flux and maintained cell survival. We developed an adult canine cardiac slice culture system appropriate for studying the effects of autophagic flux that may be applicable to drug toxicity evaluations.

Comparison of echocardiography, biomarkers and taurine concentrations in cats eating high- or low-pulse diets.

OBJECTIVES: There are ongoing investigations into diet-associated dilated cardiomyopathy in dogs, but there has been minimal investigation into possible diet-associated dilated cardiomyopathy in cats. The objective of this study was to compare cardiac size and function, cardiac biomarkers and taurine concentrations in healthy cats eating high- vs low-pulse diets. We hypothesized that cats eating high-pulse diets would have larger hearts, lower systolic function and higher biomarker concentrations than cats eating low-pulse diets and that there would be no difference in taurine concentrations between the diet groups. METHODS: Echocardiographic measurements, cardiac biomarkers, and plasma and whole-blood taurine concentrations were compared between cats eating high- and low-pulse commercial dry diets in a cross-sectional study. RESULTS: There were no differences between the high- (n = 21) and low-pulse (n = 31) diet groups with regard to age, sex and breed, but more cats in the high-pulse group were overweight or obese (67% vs 39%; P = 0.05). Diet duration was not different in the groups, but the range was wide (6-120 months). No differences were found between the diet groups for key cardiac measurements, biomarker concentrations, or plasma or whole-blood taurine concentrations. However, there were significant negative correlations between diet duration and measures of left ventricular wall thickness in the high-pulse, but not the low-pulse, diet group. CONCLUSIONS AND RELEVANCE: This study did not detect significant associations between high-pulse diets and cardiac size, function and biomarkers, but the secondary observation of significant negative correlations between time on high-pulse diets and left ventricular wall thickness warrants further evaluation.

Pathology in Practice.

In collaboration with the American College of Veterinary Pathologists.