Anesthetic synergy between two n-alkanes.

OBJECTIVE: N-butane and n-pentane can both produce general anesthesia. Both compounds potentiate γ-aminobutyric acid type A (GABAA) receptor function, but only butane inhibits N-methyl-d-aspartate (NMDA) receptors. It was hypothesized that butane and pentane would exhibit anesthetic synergy due to their different actions on ligand-gated ion channels. STUDY DESIGN: Prospective experimental study. ANIMALS: A total of four Xenopus laevis frogs and 43 Sprague-Dawley rats. METHODS: Alkane concentrations for all studies were determined via gas chromatography. Using a Xenopus oocyte expression model, standard two-electrode voltage clamp techniques were used to measure NMDA and GABAA receptor responses in vitro as a function of butane and pentane concentrations relevant to anesthesia. The minimum alveolar concentrations (MAC) of butane and pentane were measured separately in rats, and then pentane MAC was measured during coadministration of 0.25, 0.50 or 0.75 times MAC of butane. An isobole with 95% confidence intervals was constructed using regression analysis. A sum of butane and pentane that was statistically less than the lower-end confidence bound isobole indicated a synergistic interaction. RESULTS: Both butane and pentane dose-dependently potentiated GABAA receptor currents over the study concentration range. Butane dose-dependently inhibited NMDA receptor currents, but pentane did not modulate NMDA receptors. Butane and pentane MAC in rats was 39.4±0.7 and 13.7±0.4 %, respectively. A small but significant (p<0.03) synergistic anesthetic effect with pentane was observed during administration of either 0.50 or 0.75×MAC butane. CONCLUSIONS: Butane and pentane show synergistic anesthetic effects in vivo consistent with their different in vitro receptor effects. CLINICAL RELEVANCE: Findings support the relevance of NMDA receptors in mediating anesthetic actions for some, but not all, inhaled agents.

Effects of methylprednisolone, dantrolene, and their combination on experimental spinal cord injury.

This study aimed to evaluate the effect of methylprednisolone sodium succinate, dantrolene sodium, and their combination on experimental spinal cord injury. We used 25 rats (Rattus norvegicus) that were divided into five groups. The negative control group (NC) consisted of animals without spinal cord trauma. In the groups with spinal cord trauma, the positive control group (PC) was given no treatment, the MS group was treated with methylprednisolone, the MS/DS group was treated with methylprednisolone and dantrolene, and the DS group was treated with dantrolene alone. The animals' motor function was evaluated daily, as measured with the open field test. Eight days after surgery, the animals were euthanized for spinal cord collection. Descriptive morphological evaluation, anti-NeuN immunohistochemistry, TUNEL, and anti-Bax immunofluorescence were performed. There was no significant difference between the PC, MS, MS/DS and DS groups with respect to BBB scores, neuronal and glial staining, or Bax expression (P < 0.05). Therefore, we conclude that methylprednisolone sodium succinate, dantrolene sodium, or the combination of these drugs did not reduce neuronal and glial loss, intrinsic pathway apoptosis, or promote functional recovery.

Omega-conotoxin MVIIC attenuates neuronal apoptosis in vitro and improves significant recovery after spinal cord injury in vivo in rats.

Excessive accumulation of intracellular calcium is the most critical step after spinal cord injury (SCI). Reducing the calcium influx should result in a better recovery from SCI. Calcium channel blockers have been shown a great potential in reducing brain and spinal cord injury. In this study, we first tested the neuroprotective effect of MVIIC on slices of spinal cord subjected to ischemia evaluating cell death and caspase-3 activation. Thereafter, we evaluated the efficacy of MVIIC in ameliorating damage following SCI in rats, for the first time in vivo. The spinal cord slices subjected a pretreatment with MVIIC showed a cell protection with a reduction of dead cells in 24.34% and of caspase-3-specific protease activation. In the in vivo experiment, Wistar rats were subjected to extradural compression of the spinal cord at the T12 vertebral level using a weigh of 70 g/cm, following intralesional treatment with either placebo or MVIIC in different doses (15, 30 and 60 pmol) five minutes after injury. Behavioral testing of hindlimb function was done using the Basso Beattie Bresnahan locomotor rating scale, and revealed significant recovery with 15 pmol (G15) compared to other trauma groups. Also, histological bladder structural revealed significant outcome in G15, with no morphological alterations, and anti-NeuN and TUNEL staining showed that G15 provided neuron preservation and indicated that this group had fewer neuron cell death, similar to sham. These results showed the neuroprotective effects of MVIIC in in vitro and in vivo model of SCI with neuronal integrity, bladder and behavioral improvements.

Systemic effects induced by intralesional injection of ω-conotoxin MVIIC after spinal cord injury in rats.

BACKGROUND: Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes. RESULTS: The clinical, hematologic and biochemical evaluation revealed no significant abnormalities in all groups, even in high doses. There was no significant alteration in organs, except for degenerative changes in kidneys at a dose of 120 pmol. CONCLUSIONS: These findings suggest that MVIIC at 15, 30 and 60 pmol are safe for intralesional administration after spinal cord injury and could be further investigated in relation to its neuroprotective effects. However, 120 pmol doses of MVIIC may provoke adverse effects on kidney tissue.

Systemic effects induced by intralesional injection of ?-conotoxin MVIIC after spinal cord injury in rats

Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.

Systemic effects induced by intralesional injection of ?-conotoxin MVIIC after spinal cord injury in rats

Calcium channel blockers such as conotoxins have shown a great potential to reduce brain and spinal cord injury. MVIIC neuroprotective effects analyzed in in vitro models of brain and spinal cord ischemia suggest a potential role of this toxin in preventing injury after spinal cord trauma. However, previous clinical studies with MVIIC demonstrated that clinical side effects might limit the usefulness of this drug and there is no research on its systemic effects. Therefore, the present study aimed to investigate the potential toxic effects of MVIIC on organs and to evaluate clinical and blood profiles of rats submitted to spinal cord injury and treated with this marine toxin. Rats were treated with placebo or MVIIC (at doses of 15, 30, 60 or 120 pmol) intralesionally following spinal cord injury. Seven days after the toxin administration, kidney, brain, lung, heart, liver, adrenal, muscles, pancreas, spleen, stomach, and intestine were histopathologically investigated. In addition, blood samples collected from the rats were tested for any hematologic or biochemical changes.

Head trauma as a possible cause of central diabetes insipidus in a cat.

A 13-month-old female domestic shorthair cat presented with a 10-month history of polyuria and polydipsia that began after having been hit by a car. Neurological examination revealed visual deficits and an absent bilateral menace response. Hematological and serum biochemical analyses were within reference values, but hyposthenuria was identified. Failure to concentrate urine during the water deprivation test followed by an increase in urine specific gravity after administration of synthetic antidiuretic hormone (ADH) suggested a diagnosis of central diabetes insipidus. Subcutaneous or oral administration of synthetic ADH was effective in central diabetes insipidus treatment during the 19-month follow-up.

Solubility of haloether anesthetics in human and animal blood.

BACKGROUND: Anesthetic blood solubility predicts pharmacokinetics for inhaled agents and is essential for determination of blood anesthetic concentrations from end-tidal gas concentrations using Henry's Law. Though used to model anesthetic effects in humans, there are limited interspecies solubility comparisons that include modern haloethers. This study aimed to measure hematocrit-adjusted blood:gas anesthetic partition coefficients (λ B:G) for desflurane, sevoflurane, isoflurane, and methoxyflurane in humans and animals. METHODS: Whole blood was collected from 20 rats, 8 horses, and 4 each of cats, cattle, humans, dogs, goats, pigs, rabbits, and sheep. Plasma or cell volume was removed to adjust all samples to a packed cell volume of 40%. A single-agent calibration gas headspace was added to blood in a glass syringe and was mixed and equilibrated at 37°C for 2 h. Agent concentrations in the calibration gas and syringe headspace were measured using gas chromatography. Anesthetic solubility in saline, citrate-phosphate-dextrose-adenine, and olive oil were similarly measured. RESULTS: Except for goats, all animal species had at least one λ B:G measurement that differed significantly from humans. For each agent, λ B:G positively correlated with serum triglyceride concentrations, but this only explained 25% of interspecies variability. Desflurane was significantly less soluble in blood than sevoflurane in some species (e.g., humans) but not in others (e.g., rabbits). CONCLUSIONS: Anesthetic partition coefficients differ significantly between humans and most animals for haloether anesthetics. Because of their similar λ B:G values, goats may be a better animal model for inhaled anesthetic pharmacokinetics in people.

Cardiorespiratory and blood gas alterations during laparoscopic surgery for intra-uterine artificial insemination in dogs.

Cardiorespiratory and blood gas alterations were evaluated in 6 healthy dogs that underwent a laparoscopic procedure using isoflurane anesthesia and carbon dioxide (CO(2)) pneumoperitoneum for 30 min. Heart rate, respiratory rate, body temperature, venous blood pH, partial pressure of CO(2) and oxygen, oxygen saturation, total carbon dioxide (TCO(2)) and bicarbonate were monitored. Significant alterations were hypercapnia, hypoventilation, and respiratory acidosis.

Idiopathic hypertrophic osteopathy in a cat.

This report describes the first case of idiopathic hypertrophic osteopathy (HO) in a cat. No causes for the bone pathology were found following evaluation of the physical and laboratory examinations (complete blood count, albumin, creatinine, urea, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase and urinalysis), and after histopathological evaluation of organs at necropsy. Based on the radiographic, clinical and anatomopathological findings, idiopathic HO was diagnosed.