Endogenous benzodiazepine activity in the peripheral and portal blood of dogs with congenital portosystemic shunts.

OBJECTIVE

The purpose of this study was to determine whether an endogenous benzodiazepine receptor ligand (EBZ) was present in the arterial and portal blood of dogs with congenital portosystemic shunts (CPSS).

STUDY DESIGN

The presence or absence of an EBZ was determined by the collection of systemic and portal blood from dogs with CPSS.

ANIMALS

Fifteen client-owned dogs with a confirmed CPSS. All dogs had historical signs compatible with hepatic encephalopathy. Eight healthy dogs were used as controls.

METHODS

In all dogs, systemic blood samples were collected after they were anesthetized. Portal blood samples were collected intraoperatively. EBZ was measured by radioreceptor assay.

RESULTS

In 10 of 15 dogs, the portal blood concentration of EBZ was significantly elevated compared with normal dogs (mean, 13.2 +/- 18.55 ng/mL). Five dogs had elevated systemic blood EBZ levels (mean, 8.2 +/- 16.08 ng/mL). Eleven of 15 dogs had a higher portal than systemic blood concentration of EBZ. In contrast, control dogs had extremely low EBZ concentrations detected in their portal blood (mean, 0.16 +/- 0.3 ng/mL) and systemic blood (0 ng/mL). The mean portal and systemic blood concentrations in dogs with CPSS were significantly greater than in control dogs (P < .05).

CONCLUSIONS

Elevated blood levels of EBZ were found in dogs with CPSS. The portosystemic gradient noted in 11 dogs suggests the gastrointestinal tract as a possible source for the endogenous ligand.

CLINICAL RELEVANCE

Generalized motor seizures have been reported in dogs after surgical correction of CPSS. If the presence of a CPSS results in stimulation of brain receptors for benzodiazepines, post-CPSS ligation seizures may result from a withdrawal of EBZ after ligation of the portosystemic shunt.