Effect of a short-term fast on ketamine-xylazine anesthesia in rats.

Although ketamine-xylazine (KX) anesthesia is commonly used in rats, it is often reported to have an inconsistent anesthetic effect, with a prolonged induction time, an inadequate anesthetic plane, or a very short sleep time. Blood flow to the liver is known to shift after a meal in rats, perhaps explaining anesthetic variability among rats with variable prandial status. The current study tested the hypothesis that a short period of fasting (3 h) prior to induction with intraperitoneal KX anesthesia would provide a shorter time to recumbency, a longer total sleep time, and a more consistent loss of toe pinch response than would fed rats. Two groups of male Sprague-Dawley rats were used in blinded, crossover experiments. KX anesthesia was administered at 2 different doses (50 mg/kg-5 mg/kg and 70 mg/kg-7 mg/kg) after ad libitum feeding or a 3-h fast. There were no significant differences between groups in induction time, total sleep time, or loss of toe pinch response. We conclude that fasting rats for 3 h prior to KX intraperitoneal anesthesia does not affect induction time, total sleep time, loss of toe pinch response or reduce KX anesthetic variability in male Sprague-Dawley rats.

Glycogen storage disease type Ia in canines: a model for human metabolic and genetic liver disease.

A canine model of Glycogen storage disease type Ia (GSDIa) is described. Affected dogs are homozygous for a previously described M121I mutation resulting in a deficiency of glucose-6-phosphatase-α. Metabolic, clinicopathologic, pathologic, and clinical manifestations of GSDIa observed in this model are described and compared to those observed in humans. The canine model shows more complete recapitulation of the clinical manifestations seen in humans including "lactic acidosis", larger size, and longer lifespan compared to other animal models. Use of this model in preclinical trials of gene therapy is described and briefly compared to the murine model. Although the canine model offers a number of advantages for evaluating potential therapies for GSDIa, there are also some significant challenges involved in its use. Despite these challenges, the canine model of GSDIa should continue to provide valuable information about the potential for generating curative therapies for GSDIa as well as other genetic hepatic diseases.