Case report: Manual carbon hemoperfusion for the treatment of meloxicam toxicity in a cat and suspected ibuprofen toxicity in a dog.

Extracorporeal blood purification (ECBP) has become a popular treatment option for non-steroidal anti-inflammatory drug (NSAID) toxicity in small animals. However, challenges arise when using ECBP for small dogs and cats because the priming volume required by most machine-based ECBP platforms might be excessive, leading to cardiovascular instability if a blood prime is not used. This report describes the successful use of manual carbon hemoperfusion (MCHP) to reduce plasma meloxicam levels in a cat following an inadvertent overdose and its use in a dog following suspected ibuprofen ingestion. In both animals, MCHP reduced the circuit volume needed for ECBP from 125 mL with a machine-based therapeutic plasma exchange or 104 mL with an in-series carbon hemoperfusion on an intermittent hemodialysis platform to just 40-50 mL. In the cat, MCHP reduced plasma meloxicam levels by 44%, and in both animals, the use of MCHP in these pets was well-tolerated and safe. Due to pre-existing anemia, the cat required a blood transfusion but the dog did not. MCHP is technically simple and can be performed at any hospital with access to carbon filters and blood bank resources. This technique may represent a reasonable alternative to treat NSAID toxicities in animals that are too small for conventional extracorporeal decontamination methods using either machine-based platforms without using a blood prime or in locations where these machines are unavailable.

Gender-specific differences in the in situ cardiac function of endotoxemic rats detected by pressure-volume catheter.

The aim of the present study was to investigate the existence of gender-related differences in the profile of changes that occur in cardiac functionality during endotoxic shock. For this, both male and female Wistar rats received a single injection of lipopolysaccharide (LPS; 10 mg/kg, i.p.) at 6 h (LPS 6-h group) or 24 h (LPS 24-h group) before the induction of anesthesia and insertion of a pressure-volume catheter using the closed-chest method. Control animals received sterile saline. Hemodynamic parameters were recorded under basal conditions and during the peak of the pressor effect of phenylephrine (30 nmol/kg i.v.). Body temperature, hematologic parameters, blood glucose, and diuresis were also evaluated. There were unremarkable differences between male and female rats in the general aspects of sepsis evaluated in our study. Both male and female rats from the LPS 6-h group presented hypotension, depressed left ventricular ejection fraction, decreased stroke work, reduced dP/dtmax (maximal rate of left ventricle pressure change), P@dP/dtmax (pressure value at the maximum dP/dtmax), dP/dtmin (minimal rate of left ventricle pressure change), and preload-recruitable stroke work indices, as well as increased end-systolic volume. Nevertheless, only male rats from the LPS 24-h group still presented decreased stroke work and reduced dP/dtmax, P@dP/dtmax, and preload-recruitable stroke work indices. The end-systolic volume presented slight changes during the pressor effects of phenylephrine in all groups of male rats, as well as in females from the control and LPS 6-h groups, but it was significantly increased in females from the LPS 24-h group. These findings suggest that after induction of endotoxic shock female rats may recover the inotropic cardiac function earlier than males, as well as present improved adaptation of their left ventricle to the pressure-loading effects of phenylephrine.

Increased activation of the Rho-A/Rho-kinase pathway in the renal vascular system is responsible for the enhanced reactivity to exogenous vasopressin in endotoxemic rats.

OBJECTIVE: We evaluated the role of the renal vascular system and the Rho-A/Rho-kinase pathway in the maintenance of the pressor effects of vasopressin in endotoxemic rats. DESIGN: In vitro and in vivo animal study. SETTING: University research laboratory. SUBJECTS: Male Wistar rats (200-300 g). INTERVENTION: Rats received either saline or lipopolysaccharide (10 mg/kg, intraperitoneal) 6 or 24 hours before the experiments. The effects of vasopressin on isolated aortic rings, cardiac function, mean arterial pressure, and both the renal vascular perfusion pressure of perfused kidneys in vitro and renal blood flow in situ were evaluated. The role of Rho-kinase in the renal and systemic effects of vasopressin was investigated through administration of the selective inhibitor Y-27632 and Western blot analysis. MEASUREMENTS AND MAIN RESULTS: The effect of vasopressin on mean arterial pressure was unaltered and that on renal vascular perfusion pressure enhanced in endotoxemic rats at both 6 and 24 hours after lipopolysaccharide, despite reduced contractile responses in aortic rings and the lack of effect on cardiac function. Vasopressin (3, 10, and 30 pmol/kg, IV) produced increased reduction in renal blood flow in endotoxemic rats. In perfused kidneys from lipopolysaccharide groups, administration of Y-27632 reverted the hyperreactivity to vasopressin. Treatment with Y-27632 partially inhibited the effects of vasopressin on mean arterial pressure and significantly reduced the effects of vasopressin on renal blood flow in control but not in endotoxemic rats. Although the protein levels of Rho-A and Rho-kinase I and II had not been impaired, the levels of phosphorylated myosin phosphatase-targeting subunit 1, the regulatory subunit of myosin phosphatase that is inhibited by Rho-kinase, were increased in both the renal cortex and the renal medulla of endotoxemic rats. CONCLUSION: Our data suggest that activation of Rho-kinase potentiates the vascular effects of vasopressin in the kidneys, contributing to the maintenance of the hypertensive effects of this agent during septic shock.