The effect of adding lactic acid to canine whole blood on platelet aggregation as measured by impedance aggregometry.

BACKGROUND: Acidemia in sick dogs often results from the accumulation of lactic acid. The resulting decrease in blood pH can have many physiologic effects, including alteration of platelet function. OBJECTIVES: We aimed to evaluate the effect of hyperlactatemia and subsequent acidemia on platelet aggregation in canine blood using impedance aggregometry. METHODS: Platelet aggregation was measured in blood from 27 healthy dogs using the Multiplate analyzer at baseline and after in vitro addition of two different volumes of lactic acid to adjust the pH. The area under the curve (AUC), reported by the Multiplate analyzer, was used to assess the extent of platelet aggregation in each sample. A linear mixed effects model was used to test for the association between platelet aggregation and pH. The association of baseline platelet aggregation with HCTs, platelet counts, and WBC counts was assessed using Pearson's correlations. RESULTS: Acidemia was associated with a significant decrease in platelet aggregation. No significant correlations were detected between platelet aggregation and HCT, platelet count, or WBC count. Platelet aggregation measured using the Multiplate analyzer showed substantial individual variation. CONCLUSIONS: Worsening acidemia due to the addition of lactic acid caused a mild but significant decrease in platelet aggregation in canine blood. The clinical significance of this change is uncertain but could be important when combined with other abnormalities of hemostasis associated with illness.

Animal models of GM2 gangliosidosis: utility and limitations.

GM2 gangliosidosis, a subset of lysosomal storage disorders, is caused by a deficiency of the glycohydrolase, ß-N-acetylhexosaminidase, and includes the closely related Tay-Sachs and Sandhoff diseases. The enzyme deficiency prevents the normal, stepwise degradation of ganglioside, which accumulates unchecked within the cellular lysosome, particularly in neurons. As a result, individuals with GM2 gangliosidosis experience progressive neurological diseases including motor deficits, progressive weakness and hypotonia, decreased responsiveness, vision deterioration, and seizures. Mice and cats are well-established animal models for Sandhoff disease, whereas Jacob sheep are the only known laboratory animal model of Tay-Sachs disease to exhibit clinical symptoms. Since the human diseases are relatively rare, animal models are indispensable tools for further study of pathogenesis and for development of potential treatments. Though no effective treatments for gangliosidoses currently exist, animal models have been used to test promising experimental therapies. Herein, the utility and limitations of gangliosidosis animal models and how they have contributed to the development of potential new treatments are described.