Intracranial pressure monitoring in normal dogs using subdural and intraparenchymal miniature strain-gauge transducers.

BACKGROUND: Monitoring of intracranial pressure (ICP) is a critical component in the management of intracranial hypertension. Safety, efficacy, and optimal location of microsensor devices have not been defined in dogs. HYPOTHESIS/OBJECTIVE: Assessment of ICP using a microsensor transducer is feasible in anesthetized and conscious animals and is independent of transducer location. Intraparenchymal transducer placement is associated with more adverse effects. ANIMALS: Seven adult, bred-for-research dogs. METHODS: In a prospective investigational study, microsensor ICP transducers were inserted into subdural and intraparenchymal locations at defined rostral or caudal locations within the rostrotentorial compartment under general anesthesia. Mean arterial pressure and ICP were measured continuously during physiological maneuvers, and for 20 hours after anesthesia. RESULTS: Baseline mean ± SD values for ICP and cerebral perfusion pressure were 7.2 ± 2.3 and 78.9 ± 7.6 mm Hg, respectively. Catheter position did not have a significant effect on ICP measurements. There was significant variation from baseline ICP accompanying physiological maneuvers (P < .001) and with normal activities, especially with changes in head position (P < .001). Pathological sequelae were more evident after intraparenchymal versus subdural placement. CONCLUSIONS AND CLINICAL IMPORTANCE: Use of a microsensor ICP transducer was technically straightforward and provided ICP measurements within previously reported reference ranges. Results support the use of an accessible dorsal location and subdural positioning. Transient fluctuations in ICP are normal events in conscious dogs and large variations associated with head position should be accounted for when evaluating animals with intracranial hypertension.

Effect of transdermally administered fentanyl on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine the effect of two doses of fentanyl, administered transdermally, on the minimum alveolar concentration (MAC) of isoflurane in cats. STUDY DESIGN: Prospective, randomized study. ANIMALS: Five healthy, spayed, female cats. METHODS: Each cat was studied thrice with at least 2 weeks between each study. In study 1, the baseline isoflurane MAC was determined in triplicate for each cat. In studies 2 and 3, isoflurane MAC was determined 24 hours after placement of either a 25 or 50 microg hour(-1) fentanyl patch. In each MAC study, cats were instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Twenty-four hours prior to studies 2 and 3, a catheter was placed and secured in the jugular vein and either a 25 or 50 microg hour(-1) fentanyl patch was placed in random order on the left thorax. Blood samples for plasma fentanyl determination were collected prior to patch placement and at regular intervals up to 144 hours. After determination of MAC in studies 2 and 3, naloxone was administered as a bolus dose (0.1 mg kg(-1)) followed by an infusion (1 mg kg(-1) hour(-1)) and MAC redetermined. RESULTS: The baseline isoflurane MAC was 1.51 +/- 0.21% (mean +/- SD). Fentanyl (25 and 50 micro g hour(-1)) administered transdermally significantly reduced MAC to 1.25 +/- 0.26 and 1.22 +/- 0.16%, respectively. These MAC reductions were not significantly different from each other. Isoflurane MAC determined during administration of fentanyl 25 micro g hour(-1) and naloxone (1.44 +/- 0.16%) and fentanyl 50 micro g hour(-1) and naloxone (1.51 +/- 0.19%) was not significantly different from baseline MAC (1.51 +/- 0.21%). CONCLUSIONS AND CLINICAL RELEVANCE: Fentanyl patches are placed to provide long-lasting analgesia. In order to be effective postoperatively, fentanyl patches must be placed prior to surgery. Plasma fentanyl concentrations achieved intraoperatively decrease the need for potent inhalant anesthetics in cats.

Growth inhibition of an orthotopic glioblastoma in immunocompetent mice by cationic lipid-DNA complexes.

The effect of a cationic liposome non-coding plasmid DNA complex on the growth of an intracerebral glioblastoma in an immunocompetent syngeneic mouse strain was evaluated. Previous studies of extraneural tumors in mice have demonstrated that such complexes containing plasmid DNA are capable of stimulating a potent Th-1 cytokine immune-mediated response with a dramatic inhibition of tumor growth. A DOTIM-cholesterol cationic liposome complexed to non-coding plasmid DNA (EV-CLDC) was administered intravenously (i.v.) at weekly intervals to 6-week-old male mice of the B6D2F1 strain at either 3, 10 or 17 days post-inoculation (DPI) of 4C8 glioblastoma cells. Tumor growth was monitored by volumetric image analysis obtained from sequential weekly magnetic resonance imaging studies of the brain. Experiments were terminated between 30 to 38 DPI. Terminal tumor volumes calculated from histological sections directly correlated with tumor volumes from corresponding MR images. The EV-CLDC administered at 3 DPI resulted in a statistically significant (P<0.0001) sustained inhibition of tumor growth compared with tumors in mice administered only individual components of the EV-CLDC. The EV-CLDC similarly inhibited growth of longer established glioblastomas. Histopathologic evaluation of terminal tumors did not find any hemorrhage, edema or necrosis in either the EV-CLDC-treated or control tumors. The results indicate that an i.v.-administered EV-CLDC can significantly inhibit the growth of a brain tumor in immunocompetent syngeneic mice.

Effect of variable-dose propofol alone and in combination with two fixed doses of ketamine for total intravenous anesthesia in cats.

OBJECTIVE: To determine the minimum infusion rate (MIR50) for propofol alone and in combination with ketamine required to attenuate reflexes commonly used in the assessment of anesthetic depth in cats. ANIMALS: 6 cats. PROCEDURE: Propofol infusion started at 0.05 to 0.1 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine (low-dose ILD] constant rate infusion [CRI] of 23 microg/kg/min or high-dose [HD] CRI of 46 microg/kg/min), and after 15 minutes, responses of different reflexes were tested. Following a response, the propofol dose was increased by 0.05 mg/kg/min for propofol alone or 0.025 mg/kg/min for propofol and ketamine, and after 15 minutes, reflexes were retested. RESULTS: The MIR50 for propofol alone required to attenuate blinking in response to touching the medial canthus or eyelashes; swallowing in response to placement of a finger or laryngoscope in the pharynx; and to toe pinch, tetanus, and tail-clamp stimuli were determined. Addition of LD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, finger, toe pinch, and tetanus stimuli but did not change those for laryngoscope or tail-clamp stimuli. Addition of HD ketamine to propofol significantly decreased MIR50, compared with propofol alone, for medial canthus, eyelash, toe pinch, tetanus, and tail-clamp stimuli but did not change finger or laryngoscope responses. CONCLUSIONS AND CLINICAL RELEVANCE: Propofol alone or combined with ketamine may be used for total IV anesthesia in healthy cats at the infusion rates determined in this study for attenuation of specific reflex activity.

Technical parameters affecting image characteristics in in vivo MR microscopy of the mouse.

The aim of the study was to assess the effects of changing acquisition parameters used for high-resolution in vivo magnetic resonance (MR) microscopy on image quality and scan time. The head or abdomen of 11 normal and 1 glioblastoma-bearing anesthetized BALB/c mice were imaged using a high-resolution 7.0-Tesla magnet. Scan parameters such as matrix size (MTX), slice thickness (ST), number of excitations (NEX), pulse sequence type including repetition time (TR) and echo time (TE), respiratory gating, and intraperitoneal contrast medium administration were altered to assess their actual effect on signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) as compared to calculated effects. As expected, SNR increased with increasing ST or NEX and with decreasing MTX. However, although the empirical increase in SNR was similar to that expected for increased ST, it was less than that anticipated for increasing NEX or decreasing MTX. Increasing NEX and applying respiratory gating both increased SNR and reduced the image degradation associated with respiratory motion in images of the abdomen. Intraperitoneal contrast medium administration produced a marked increase in CNR in the subject with the implanted glioblastoma, suggesting that this route is satisfactory for the enhancement of lesions disrupting the blood-brain barrier. The consequence of improving image quality in terms of spatial and contrast resolution is increased scan time. However, the actual increase in SNR when altering acquisition parameters may not be as much as predicted by theory.

Effects of morphine, butorphanol, buprenorphine, and U50488H on the minimum alveolar concentration of isoflurane in cats.

OBJECTIVE: To determine whether opioids with varying interactions at receptors induce a reduction in minimum alveolar concentration (MAC) of isoflurane in cats. ANIMALS: 12 healthy, female, spayed cats. PROCEDURE: Cats were anesthetized with isoflurane and instrumented to allow collection of arterial blood and measurement of arterial blood pressure. Each drug was studied separately, and for each drug cats were randomly allocated to receive 2 doses. The drugs studied were morphine (0.1 or 1.0 mg/kg), butorphanol (0.08 or 0.8 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg). All drugs were diluted in 5 ml of saline (0.9% NaCl) solution and infused IV for 5 minutes. The MAC of isoflurane was determined in triplicate, the drug administered, and the MAC of isoflurane redetermined for a period of 3 hours. RESULTS: All drugs had a significant effect on MAC over time. With morphine only, the effect on MAC over time was different between doses. The greatest mean (+/- SD) reductions in MAC of isoflurane in response to morphine, butorphanol, buprenorphine, and U50488H administration were 28 +/- 9, 19 +/- 3, 14 +/- 7, and 11 +/- 7%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Morphine (1.0 mg/kg) and butorphanol (0.08 and 0.8 mg/kg) induced significant reductions in MAC of isoflurane that were considered clinically important. Although significant, reductions in MAC of isoflurane induced by morphine (0.1 mg/kg), buprenorphine (0.005 and 0.05 mg/kg), and U50488H (0.02 and 0.2 mg/kg) were not considered clinically relevant because they fell within the error of the measurement technique. Administration of morphine or butorphanol decreases the need for potent inhalant anesthetics in cats and could potentially be beneficial in combination with inhalants.