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A Comparison of the Direct Cerebral Vasodilating Potencies of Halothane and Isoflurane in the New Zealand White Rabbit. By Drummond JC, Todd MM, Scheller MS, and Shapiro HM. Anesthesiology 1986; 65:462–7. Reprinted with permission. Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent–induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMRO2) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMRO2 of 3.21 ± 0.17 (SEM) ml · 100 g–1 · min–1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMRO2 of 1.76 ± 0.16 ml · 100 g–1 · min–1. In rabbits receiving a background of morphine sulfate/N2O, halothane resulted in a significantly greater CBF (65 ± 10 ml · 100 g–1 · min–1) than did isoflurane (40 ± 5 ml · 100 g–1 · min–1). Both agents caused a reduction in CMRO2, but CMRO2 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane. With halothane, CBF increased from 22 ± 2 ml · 100 g–1 · min–1 in the control stage to 39 ± 3, and with isoflurane from 24 ± to 38 ± 2 ml · 100 g–1 · min–1. CMRO2 was not depressed further by either halothane or isoflurane. These results suggest that the relative effects of halothane and isoflurane on CBF are dependent on the CMR present prior to their administration. When the preexistent CMR is not markedly depressed, isoflurane decreases CMR and causes less cerebral vasodilation than does halothane. When initial CMR is depressed, halothane and isoflurane have similar vasodilating potencies.

PURPOSE This pilot study examines the rates of exposure and fibrovascular ingrowth of silicone-capped, porous, polyethylene orbital implants in the New Zealand white rabbit animal model. METHODS Unwrapped, silicone-capped, porous, polyethylene orbital spheres were implanted in 16 enucleated rabbit orbits. Four implants were removed at 3, 6, 9, and 12-month intervals and submitted for histopathologic analysis. A board-certified pathologist reviewed and graded vascular ingrowth, inflammation type, and severity for all specimens. RESULTS Fibrovascular ingrowth in the center of all implants occurred as early as 3 months. No fibrovascular ingrowth occurred at the interface between the silicone cap and the porous polyethylene implant. The overlying Tenon's and conjunctival tissues remained intact without significant host inflammatory response. No implant exposure occurred at any time point. CONCLUSIONS Silicone-capped porous polyethylene orbital implants appear to offer an inexpensive, easy-to-manufacture implant that resists exposure without the need for a wrapping material and achieves successful biointegration soon after implantation.

BACKGROUND: Cartilage graft is an effective method for reconstructing the bony framework of the face and covering the bony defect site. As a process method of cartilages, lyophilization has the advantages of long-term storage and easy handling. We hypothesized that the type of procedure used to sterilize lyophilized cartilage may affect outcomes after implantation into the body. We compared the effects of ethylene oxide (EO) gas, γ-irradiation, and autoclaving methods on cartilage grafts. METHODS: After sterilization, lyophilized human rib cartilage was inserted into subperiosteal pockets created in New Zealand white rabbit skulls. We assessed the weights and ratios of the remaining cartilage and examined histologic changes throughout the implantation period. RESULTS: Over a 5-week period, the γ-irradiated grafts remained more than the other grafts, but after more than 5 weeks, there were no significant differences between γ-irradiated and EO gas-sterilized cartilages. Autoclave-sterilized cartilages were totally resorbed at 10 weeks. CONCLUSIONS: Over 10 weeks of follow-up, based on persistence measurements and histologic appearance, there was little difference between γ-irradiated and EO gas-sterilized lyophilized cartilage used in experimental bone grafts.

STUDY DESIGN Posterolateral lumbar spine fusions in New Zealand white rabbits. OBJECTIVE To evaluate the efficacy of recombinant human growth and differentiation factor-5 (rhGDF-5) lyophilized to a Healos carrier (cross-linked type I collagen with hydroxyapatite coating; DePuy Spine, Inc., Raynham, MA) in inducing fusion. SUMMARY OF BACKGROUND DATA Bone graft substitutes have become an area of considerable interest. rhGDF-5 is one such product. Limited lumbar preclinical studies have been performed with this product. METHODS Single-level, intertransverse process fusions were performed in 67 rabbits using iliac crest autograft (n = 13), Healos alone (n = 13), or 0.5, 1.0, or 1.5 mg/cc rhGDF-5 lyophilized to Healos (n = 13 per group). At 8 weeks, the rabbits were euthanized. Fusion masses were assessed. RESULTS There were 2 animals (3%) lost to complication. Manual palpation revealed fusion rates for autograft of 38% (5/13), Healos alone of 0% (0/13), and each of the Healos/rhGDF-5 groups of 100% (13/13). Histologic analyses were 95% sensitive and 95% specific for confirming fusion. Histologic differences were found among the treatment groups. CONCLUSIONS In this rabbit fusion model, Healos/rhGDF-5 induced fusion in 100% of the rabbits studied. This rate was significantly higher than the fusion rate induced by autograft (38%). Overall, these results support continued research of Healos/rhGDF-5 as a potential bone graft alternative.

Purpose To investigate the cytotoxicity of triamcinolone acetonide (TA) suspensions to corneal endothelial cells (CECs). Setting Department of Ophthalmology, Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan. Methods New Zealand white rabbit CECs were exposed for 1 minute to balanced salt solution (BSS); commercial TA suspension (cTA); vehicle-removed TA (–vTA); pure vehicle (V); 1/10 dilutions of cTA, –vTA, or V in BSS; or benzyl alcohol (BA) (cTA preservative) 9 mg/mL. Corneal endothelial cell toxicity was assessed by light microscopy (trypan blue staining) and transmission electron microscopy. The effects of 3-, 10-, or 30-minute exposures to 1/10 cTA, 1/10 –vTA, or V were also investigated. Results One-minute exposures to –vTA or 1/10 –vTA did not damage CECs; however, cTA, V, or 1/10 dilutions of cTA or V caused damage and cells exposed to BA showed severe ultrastructural damage/lysis. A 30-minute exposure to 1/10 –vTA did not cause significant cell damage, whereas 3- to 30-minute exposures to 1/10 cTA or V showed significant time-dependent cytotoxicity. Conclusions Commercial TA suspension was cytotoxic to cultured rabbit CECs because of the preservative, BA, in the vehicle. Because 1/10 –vTA appeared to be safe for up to 30 minutes of exposure, use of 1/10 dilutions of vehicle-removed TA is suggested to help surgeons visualize prolapsed vitreous during anterior vitrectomy in complicated cataract surgeries.

Data from animals have revealed that osteogenic protein-1 induces solid intertransverse process fusion more reliably than autograft, and has motivated the question: What is the difference in the fusion bed environment engendered by the addition of osteogenic protein-1? To address this question, an established New Zealand White rabbit model of spinal arthrodesis was used to evaluate the effect of iliac crest autograft, and alternatively osteogenic protein-1, on cytokine gene expression in the developing spinal fusion mass. The autograft group and the osteogenic protein-1 group had a similar pattern of gene expression for most of the cytokines investigated, highlighting the finding that the application of one bone morphogenetic protein to the fusion bed results in nearly the same gene expression as that resulting from application of autologous bone. Some differences in cytokine expression were observed at the fusion bed with the addition of osteogenic protein-1. The increased level of expression of particular osteogenic, chondrogenic, and angiogenic growth factors at the later stages of fusion may be responsible for the improved rate of solid fusion with osteogenic protein-1 as compared with autograft alone. Sequences for bone morphogenetic protein-5 and bone morphogenetic protein-7 were determined, and their respective expression in the developing spinal fusion mass was observed for the first time.

Background— The mechanisms of thrombosis on plaque erosion are poorly understood. We examined the potential role of endothelial apoptosis in endothelial erosion and vessel thrombosis. Methods and Results— Segments of New Zealand White rabbit femoral arteries were temporarily isolated in vivo. One artery was incubated with staurosporin for 30 minutes, whereas the contralateral artery was incubated with saline and served as control. Three days later, thrombosis was evaluated angiographically and histologically. TUNEL score in the endothelial layer was significantly increased in staurosporin-treated arteries compared with controls (2.43±0.30 versus 0.93±0.44, respectively; P =0.001). Large areas of endothelial denudation were detectable in staurosporin-treated vessels, whereas endothelium integrity was almost preserved in the saline group. Vessel thrombosis occurred in 58% of staurosporin-treated arteries (7 of 12) but in only 8% of saline-treated segments ( P P =0.04). These results were confirmed in balloon-injured atheromatous arteries. Conclusions— In vivo induction of endothelial apoptosis leads to both vessel thrombosis and endothelial denudation. Endothelial apoptosis may be a critical step in the transition from a stable endothelialized plaque to plaque erosion and thrombosis.

Background— HMG-CoA reductase inhibitors reduce the incidence of cardiovascular disease predominantly by their LDL-lowering effect. Recently, there has been great interest in the pleiotropic effects of statins, which appear to differ among the various agents in this class. Unlike other statins, atorvastatin exhibits a decline in its HDL-raising effect at higher doses in humans. Whether atorvastatin-mediated alterations in HDL turnover in vivo contribute to this effect has not previously been investigated. We therefore studied the effect of atorvastatin on HDL apolipoprotein (apo) A-I production and clearance in normolipidemic male New Zealand White rabbits. Methods and Results— Kinetic studies of HDL-apoA-I radiolabeled with 131 I were performed in chow-fed rabbits after 3 weeks of atorvastatin treatment of 5 mg · kg −1 · d −1 (n=7) versus placebo-treated rabbits (n=7). Our results showed a significantly ( P −1 · h −1 , P =0.06). Accordingly, plasma apoA-I levels in atorvastatin-treated animals declined significantly ( P Conclusions— These data suggest that the effect on apoA-I levels observed with atorvastatin at higher drug doses in humans may be caused at least in part by enhanced HDL apoA-I catabolism, which is not entirely offset by a concomitant increase in apoA-I production. Whether this finding results from an effect of atorvastatin on HDL particle composition or on receptors involved in circulating HDL holoparticle clearance will require further study.

Purpose To correlate the observed fluorescence spectrum with the depth of ablation during 193 nm argon−fluoride excimer laser ablation of chemically damaged corneas. Setting Laser facility, Cedars-Sinai Medical Center, Los Angeles, California, USA. Methods Three cadaver New Zealand white rabbit corneas were exposed to 1 N hydrogen chloride for 10 seconds. The resultant opaque corneas were ablated to perforation using the excimer laser. Laser-induced fluorescence was collected at 45 degrees from incidence and channeled into an ultraviolet-visible spectrometer coupled to an optical multichannel analyzer reading a diode array detector. The detector recorded single-shot fluorescence spectra. The data were examined by principal component analysis, and the evolution of eigenvectors and their weighting coefficients were used to compare data among corneas. The results were correlated with histopathological sections. Results The eigenvalues of 3 principal components corresponded to 88.9%, 10.0%, and 0.4% of the data in acid-burned corneas. Compared to that in undamaged corneas, more information was stored in the first principal component and the third eigenvector was distinctly altered. Acid-scarred tissue blue shifted the dominant fluorescence peak compared to that in normal corneal tissue. Conclusions After severe hydrogen chloride burn to the rabbit corneal surface, monitoring the dominant peak wavelength shift of excimer-laser-induced fluorescence can detect the transition between severely acid-damaged and underlying tissue.

The aim of the present study was to evaluate the possibility of mobilizing calvarial bone with a fully implantable and bioresorbable device. The animal model used was the New Zealand white rabbit (n = 12). An island bone flap attached to the dura mater was created in the parietal region and amalgam markers were placed in this bone flap and in the ipsilateral frontal bone. In one group of six rabbits (group 1), a specially processed contractile 70L/ 30D,L polylactic acid plate, 15 X 6 X 0.6 mm, was attached to the island flap by one extremity, and to the fixed ipsilateral frontal bone by the other. In group 2 (control), no plate was added. Bone marker movement was followed with serial radiography. In group 1, there was a progressive reduction in mean marker distance over the first 48 hours, and stability thereafter. In group 2 (control), mean marker distance remained stable until the second postoperative week, after which time there was a slight increase until the end of the experimental period. At 4 weeks, the mean marker separation differed significantly between group 1 (mean, -3.62 mm; SD, 0.79 mm) and group 2 (mean, 0.34 mm; SD, 0.14 mm; p

OBJECTIVE: To develop a method by which a single impact force of controlled magnitude and rate could be applied uniformly to an area on the posterior aspect of the medial femoral condyle of adult rabbits. DESIGN: An in-vivo animal model using a pendulum device, designed and manufactured to supply the kinetic energy necessary to apply different impact loads to the posterior aspect of the medial femoral condyle of a rabbit. SETTING: Biomechanical laboratory, University Medical Center. SUBJECTS: A total of thirty-six femoral condyles from 3-kilogram New Zealand White (NZW) rabbits were used during this evaluation. INTERVENTION: An aluminum impactor was made based on the sagittal and coronal radii of curvature of six matched pairs (n = 12) of femurs from three-kilogram NZW rabbits. This impactor was coupled with the pendulum and used to apply different impact loads to both of the medial femoral condyle of the knees of NZW rabbits (n = 24). MAIN OUTCOME MEASUREMENTS: Peak impact force, time to peak impact force, and average contact area between impactor and medial femoral condyle, were measured for each group of animals tested. RESULTS: The pendulum delivered a consistent impact force to the rabbit condyle of 120.0 N (+/-18.1; coefficient of variance, 15 percent) with 400 grams attached to the pendulum arm, at an average time to peak force of 0.021 seconds (+/-0.001, co. var. 4.8 percent). The peak impact force was significantly different for each of the three impact mass groups of animals (p < 0.001). By contrast, time to peak force for each mass group averaged approximately 0.020 seconds and the average contact area was 6.26 mm2 (+/-0.51). Quantitative assessment of the exposed medium pressure-sensitive film confirmed uniform impact force intensity within each specimen. CONCLUSIONS: An in-vivo animal model was developed to deliver a controlled and rapid impact force to a specific area of the weight-bearing surface of the adult rabbit knee. These loads were applied at a rate comparable to the clinical setting of falling onto an outstretched hand, thus simulating a common clinical scenario by which cartilage is often injured. This model can be used in future experiments to investigate mechanism by which posttraumatic arthritis develops after articular injuries.

The precise biochemical mechanisms underlying the reduction of HDL levels in hypertriglyceridemic states are currently not known. In humans, we showed that triglyceride (TG) enrichment of HDL, as occurs in hypertriglyceridemic states, enhances the clearance of HDL-associated apolipoprotein A-I (apoA-I) from the circulation. In the New Zealand White rabbit (an animal model naturally deficient in hepatic lipase [HL]), however, TG enrichment of HDL is not sufficient to alter the clearance of either the protein or lipid moieties of HDL. In the present study, therefore, we determined in the New Zealand White rabbit the combined effects of ex vivo TG enrichment and lipolytic transformation of HDL by HL on the subsequent metabolic clearance of HDL apoA-I. Results of the in vivo kinetic studies (n=18 animals) showed that apoA-I associated with TG-enriched rabbit HDL modified ex vivo by catalytically active HL was cleared 22% more rapidly versus TG-enriched HDL incubated with heat-inactivated HL, and 26% more rapidly than fasting (TG-poor) HDL incubated with active HL ( P P

Background: Histologic delineation of the events involved in the development of long bones and the developmental age at which these events occur is needed to elucidate the genetic and molecular mechanisms associated with these events. This report describes the sequence of histologic events involved in the formation of long bones and their epiphyses in the New Zealand White rabbit. Methods: Prenatal studies were performed on twelve, fourteen, fifteen, sixteen, eighteen, twenty-one, twenty-four, and twenty-seven-day-old rabbit embryos, and postnatal studies were performed on newborn rabbits and on three-to-four-day-old; one, two, four, and six-week-old; and two, three, four, six, and eight-month-old rabbits. Histologic specimens from embryos were embedded in plastic and stained with toluidine blue or safranin O-fast green, and specimens from postnatal rabbits were embedded in paraffin and stained with hematoxylin and eosin or safranin O-fast green. Results: Studies of twelve-day-old embryos demonstrated upper and lower limb buds filled with undifferentiated mesenchymal cells, and studies of fourteen-day-old embryos showed mesenchymal condensation and beginning cartilage formation outlining major long bones. Long-bone and epiphyseal development progressed through sixteen structural stages, and the developmental age at which these stages occurred was determined. These stages included limb-bud formation with uniform distribution of mesenchymal cells and formation of an apical ectodermal ridge (stage 1); mesenchymal condensation (stage 2); cartilage differentiation (stage 3); formation of a primary center of ossification (stage 4a); epiphyseal cartilage vascularization with formation of cartilage canals (stage 7); vascular invasion of the developing secondary ossification center (stage 9); bone formation and marrow cavitation in the secondary ossification center with formation of hematopoietic marrow (stage 10); fullest relative extent of secondary-ossification-center development in epiphyseal cartilage (stage 14); thinning of the physis (stage 15); and resorption of the physis with establishment of continuity between epiphyseal and metaphyseal circulations (stage 16). Clinical Relevance: The detailed classification system presented here will allow for correlations between genetic and molecular mechanisms and histologic events in normal and abnormal development of long bones and their epiphyses. Many of the nonosseous structures formed during long-bone and epiphyseal development in the fetus, infant, and child are amenable to assessment with sonography and magnetic resonance imaging. An understanding of the histopathological features of developmental abnormalities of the long bones and their epiphyses revealed with newer imaging techniques should greatly improve management by allowing earlier diagnosis.

Study design Biomechanics of posterolateral spinal fusion were studied in an in vivo rabbit model. Objectives To determine the extent of stabilization produced by posterolateral lumbar fusion and to test the hypothesis that motions are not completely eliminated after successful fusion. Summary of background data Previous human cadaveric studies, clinical studies, and animal studies have attempted to characterize the biomechanics of posterolateral fusion. Such studies have been limited by either methods of fusion modeling or methods of stability testing. No previous study has examined biologic fusion with a physiologic biomechanical testing technique. Methods Ten adult New Zealand white rabbits underwent L5-L6 intertransverse process fusion using autogenous iliac crest bone graft. Rabbits were killed 5 weeks after surgery. Only one time point was studied. This time point was chosen because previous pull-apart studies have shown plateauing of rabbit fusion mass strength and stiffness around this time. Spines were then harvested and evaluated with manual palpation and an established flexibility testing protocol. Resulting data were compared with previously acquired, nonoperative spine flexibility data. Results Two animals were excluded because of complications. Of those that were fused (n = 5), biomechanical testing revealed significant decreases in flexion (81%), extension (61%), and right and left lateral bending (67% and 83%, respectively) (P Conclusions These findings define the amount of motion reduction that can be expected with posterolateral fusions in the rabbit model at 5 weeks. These results suggest that motion was significantly decreased but was not eliminated.

Purpose: The rabbit urinary bladder’s early response to partial outlet obstruction includes bladder wall remodeling with marked urothelial and fibroblast hyperplasia (1 day) and smooth muscle hypertrophy (3–5 days) resulting in a 4–5 fold increase in bladder mass within 7 days. In this study, we examined the effect of partial outlet obstruction on bladder blood flow during the initial period of rapid growth (1–7 days).Materials and Methods: Each New Zealand White rabbit was partially obstructed by tying a 2-0 silk ligature loosely around the vesical outlet. After 0 (unoperated), 4 hours, 1, 3, or 7 days of obstruction, 5 rabbits per group were anesthetized and the carotid and femoral arteries cannulated with polyethylene tubing. Additional rabbits receiving sham surgeries were treated like obstructed animals at 4 hours and 1 day post-obstruction (5/group). Using standard methods, fluorescent microspheres were infused through the right carotid artery. Bladder and right kidney were rapidly removed upon comp...

Background —These studies were initiated to confirm that high-level thrombomodulin overexpression is sufficient to limit neointima formation after mechanical overdilation injury. Methods and Results —An adenoviral construct expressing thrombomodulin (Adv/RSV-THM) was created and functionally characterized in vitro and in vivo. The impact of local overexpression of thrombomodulin on neointima formation 28 days after mechanical overdilation injury was evaluated. New Zealand White rabbit common femoral arteries were treated with buffer, viral control, or Adv/RSV-THM and subjected to mechanical overdilation injury. The treated vessels (n=4 per treatment) were harvested after 28 days and evaluated to determine intima-to-media (I/M) ratios. Additional experiments were performed to determine early (7-day) changes in extracellular elastin and collagen content; local macrophage, T-cell, and neutrophil infiltration; and local thrombus formation as potential contributors to the observed impact on 28-day neointima formation. The construct significantly decreased neointima formation after mechanical dilation injury in this model. By histological analysis, buffer controls exhibited mean I/M ratios of 0.76±0.06%, whereas viral controls reached 0.77±0.08%; in contrast, Adv/RSV-THM reduced I/M ratios to 0.47±0.06%. Local inflammatory infiltrate decreased in the Adv/RSV-THM group relative to controls, whereas matrix remained relatively preserved. Rates of early thrombus formation also decreased in Adv/RSV-THM animals. Conclusions —This construct thus offers a viable technique for promoting a locally neointima-resistant small-caliber artery via decreased thrombus bulk, normal matrix preservation, and decreased local inflammation without the inflammatory damage that has limited many other adenoviral applications.

PURPOSE To improve the surface visibility of perfluoroperhydrophenanthrene, we added various percentages of perfluoro-n-octane. METHODS Twenty New Zealand white rabbit eyes underwent gas vitrectomy. One milliliter of balanced salt solution was injected into each Group 1 eye as control. Perfluoro-n-octane was added to perfluoroperhydrophenanthrene in ratios of 15:85, 25:75, and 50:50; 1 mL of each mixture was injected into the vitreous cavities of Groups 2, 3, and 4, respectively. Eyes were examined clinically and electroretinograms were performed before and 4 and 8 weeks after injection, when the rabbits were killed. Eyes were processed for light and transmission electron microscopy (TEM). RESULTS The indices of refraction of the 15:85, 25:75, and 50:50 mixtures were 1.3275, 1.3191, and 1.3026, respectively, and the mixtures were visible in the vitreous cavity. Emulsification and mild-to-moderate dust-like opacities were observed in eyes from Groups 2 through 4; vitreous strands formed in four of the Group 4 eyes. The retinae were attached. Electroretinographic responses were normal, except in one eye with cataract. Light microscopy showed normal retinal architecture, with some macrophages with intracytoplasmic vacuoles on the surface of the inferior retina or in the vitreous cavity. Fingerprint disfigurement of photoreceptor outer segments was seen in some Group 3 and 4 eyes under TEM. CONCLUSIONS Minimal changes were induced by the 15:85 mixture in the rabbit eye. The mixtures of 25:75 and 50:50 produced some ultrastructural changes of the retina. The mixtures were visible under water.

Study Design. This study was designed to characterize the effects of phospholipase A 2 on the neural response of dorsal root and dorsal root ganglion in the anesthetized New Zealand White rabbit. Objectives. To examine the effects of phospholipase A? on the neural response of somatosensory neurons at the dorsal root ganglion level. of Background Data. Phospholipase A 2 may be an irritating component of disc tissue that is present in high concentration in painful herniated discs, in synovial fluids, and in sera of rheumatoid arthritis patients. Phospholipase A 2 is inflammatory; however, its effects on dorsal roots and dorsal root ganglion response have never Deen demonstrated. Methods. Surgically isolated dorsal roots and dorsal root ganglia from New Zealand White rabbits were investigated by electrophysiologic techniques. Phospholipase A 2 doses ranging from 100 to 400 U were applied on the mechanicallv sensitive segments of the dorsal root ganglia, and responses to varying doses were evaluated in relation to elapsed time. Results. The application of phospholipase A 2 on the dorsal root ganglion resulted in possible neurotoxicity at doses more than 375 U, with no significant effect at lower doses except for recruitment of silent units at doses ranging from 200 to 340 U. Conclusions. Phospholipase A 2 doses comparable to serum concentrations in human rheumatoid arthritis appeared to be neurotoxic when applied to dorsal root ganglia. At lower doses, silent units become activated that were not active before the phospholipase A 2 application. These results suggest that dorsal roots and dorsai root ganglion may be impaired by phospholipase A 2 , leading to sciatica and low back pain.

OBJECTIVE To determine regional cerebral water content in vivo by magnetic resonance imaging (MRI) after the administration of 7.5% saline in brain-lesioned rabbits. DESIGN Randomized, controlled, intervention trial. SETTING University animal laboratory. SUBJECTS Eighteen male New Zealand white rabbits, randomly assigned to one of three groups. INTERVENTIONS The animals were anesthetized (1% halothane), intubated, and mechanically ventilated to maintain end-tidal CO2 tension between 30 and 35 mm Hg (4 and 4.7 kPa). Arterial and central venous catheters were inserted and arterial blood samples were serially obtained during the experiment. Serum osmolality was measured. A cryogenic cerebral lesion was produced by pouring liquid nitrogen for 1 min into a funnel placed on the intact skull over the right hemisphere. One group of animals received 20 mL of 7.5% saline intravenously 150 mins after the cerebral lesion was generated (7.5% saline group, n = 7). A second group of animals received the same volume of 0.9% saline intravenously (0.9% saline group, n = 7). In a third group of animals (control group, n = 4) no lesion was created and no fluid administered. MEASUREMENTS AND MAIN RESULTS Five spin-echo T2-weighted MRIs of the brain were acquired at 90 mins (Baseline 1), 120 mins (Baseline 2), 150 mins (Infusion), 180 mins (Infusion + 30 mins), and 210 mins (Infusion + 60 mins) after the generation of the cerebral lesion. In the control group, two scans separated by a time interval of 120 mins were performed. The percent changes in signal intensity between the first and the four following scans of a coronal slice of the central region were determined. Analysis of variance and the Mann-Whitney U test were used for statistical analysis. Data are presented as mean +/- SD; p < .05 was considered significant. Serum osmolality increased significantly from 308 +/- 13 mosm/L to 349 +/- 19 mosm/L after the infusion of 20 mL of 7.5% saline, but did not change after the administration of 0.9% saline. Signal intensity in the area between the caudal edge of the core of the lesion and the basal ganglia was 9 +/- 8% higher on the injured side than in the corresponding area on the contralateral side (p < .05). Compared with Baseline 1, signal intensity at Infusion + 60 mins decreased by 26.3 +/- 13.7% in the 7.5% saline group, whereas it decreased by 10.4 +/- 8.6% in the 0.9% saline group (p < .05 between groups). Signal intensity decreased only slightly and nonsignificantly by 0.6 +/- 4.4% between the two scans in the control group. CONCLUSIONS The administration of a 7.5% saline solution causes a prompt and substantial decrease in cerebral water content as assessed by spin-echo T2-weighted MRI. Magnetic resonance imaging offers the opportunity for repeated, noninvasive in vivo determinations of cerebral water content.

Abstract Following our report that administration of 4-diethoxyphosphorylmethyl-N-(4-bromo-2-cyanophenyl) benzamide (NO-1886) to rats elevated postheparin lipoprotein lipase (LPL) activity through an increase in the enzyme mass, we now investigate antiatherogenic effects of NO-1886 in cholesterol-fed New Zealand White rabbits. For 20 weeks, four groups of male rabbits received regular rabbit chow (the normal control), 0.25% cholesterol-containing chow (the control), and cholesterol chow supplemented with 0.5% and 1.0% NO-1886, respectively. Postheparin LPL activity at week 10 was raised by 30% in 0.5% of the NO-1886 group and 40% in 1.0% of the NO-1886 group compared with those in the control. The area under the curve of plasma cholesterol level was not different in three cholesterol-fed groups whereas the area under the curve of HDL cholesterol was approximately twofold greater in the two NO- 1886 groups than in the control, and the area under the curve of plasma triglyceride was reduced to the level of the normal control. LPL activity was correlated with HDL cholesterol ( r =.764, n=18) and triglyceride ( r =−.627, n=18). Relative atheromatous area, aortic cholesterol, and triglyceride contents were reduced to approximately 25%, 60%, and 55%, respectively, of the control values by NO-1886 ingestion. Multiple regression analysis of LPL, HDL cholesterol, and triglyceride indicated that HDL cholesterol was the most powerful protector against aortic cholesterol accumulation, and triglyceride was the one to protect against the atheromatous area. We concluded that NO-1886 prevented the development of atherosclerosis through increasing LPL activity with a consequent increase in HDL cholesterol and a decrease in triglyceride without a significant influence of plasma cholesterol level.

Hypoxic injury is a major cause of tubular necrosis in the corticomedullary junction of isolated perfused kidneys, and is ameliorated by inhibitors of active reabsorption, such as frusemide. Our objective was to determine whether frusemide has a similar effect on hypothermically stored transplanted kidneys and whether this effect is modulated by impermeant solutes included in the preservation solution. The effect of frusemide on cytochrome oxidase (cyt aa3) oxidation, renal hemodynamics, and morphology was investigated in the New Zealand White rabbit renal autograft model using near-infrared spectroscopy and light microscopy. A total of 30 kidneys were autografted in six groups. Kidneys were transplanted with or without frusemide either (1) without storage (groups 1 and 2) or after 72 hr of storage in: (2) hypertonic citrate containing mannitol (groups 3 and 4); and (3) hypertonic citrate containing polyethylene glycol (PEG) (groups 5 and 6). In unstored transplanted kidneys, frusemide infusion stimulated a significant (P < 0.05) increase in hemoglobin oxygenation, compared with untreated controls. There was a tendency for cyt aa3 to become reduced, but there were no significant differences between groups 1 and 2. After 72 hr of storage, frusemide infusion stimulated a significant increase in hemoglobin oxygenation in kidneys stored in mannitol (P < 0.005), but there was no significant change in the kidneys stored in PEG. There was a corresponding reduction in cyt aa3 in kidneys stored in mannitol (P < 0.05) but no change in those stored in PEG. These results suggest that frusemide has a significant effect on cortical hemoglobin oxygenation in transplanted kidneys and on active reabsorption in the corticomedullary junction. The selection of impermeant is important and mannitol is significantly superior to PEG in this model.

Purpose: The aim of this study was to explore the possible etiologic relationship of hypercholesterolemia and atherosclerosis to corporal veno-occlusive dysfunction.Materials and Methods: In the New Zealand White rabbit, the competence of the corporal veno-occlusive mechanism was examined at various intervals after exposure to control diet, high cholesterol diet, or aortoiliac atherosclerosis.Results: Initially, all animals showed normal erectile function and corporal veno-occlusion. After 8 weeks and 16 weeks, the control animals preserved normal erection and corporal veno-occlusion, while most of the hypercholesterolemic and atherosclerotic animals developed corporal veno-occlusive dysfunction. The incidence of corporal veno-occlusive dysfunction in the hypercholesterolemia and atherosclerotic animals increased with time.Conclusions: This study suggests that a close relationship exists between prolonged atherosclerotic occlusion of major penile arteries and the development of corporal veno-occlu...

The significance of poor medullary reperfusion in the etiology of acute tubular necrosis during renal transplantation is poorly understood. Our objective was to determine the kinetics of renal hemoglobin oxygenation using near-infrared spectroscopy during renal transplantation, to provide a framework against which the timing of mitochondrial dysfunction could be considered. New Zealand White rabbit kidneys were flushed with hypertonic citrate solution (0-2 degrees C and autografted immediately (group 1) or stored at 0-2 degrees C for 72 hours before autografting (group 2). Changes in oxyhemoglobin (HbO2) and deoxyhemoglobin (Hb) were monitored by near-infrared spectroscopy for 3 hours of reperfusion. Intrarenal perfusion was evaluated separately by barium sulfate angiography. Reperfusion resulted in rapid increases in HbO2 within 1 minute in both groups. Group 1 HbO2 fell sharply to a minimum at 3 minutes but recovered by 20 minutes; group 2 changes were similar, but there was no recovery (P

Study Design. The present study was designed to characterize the effect of phospholipase A 2 on the discharge of perispinal sensory nerves in the anesthetized New Zealand white rabbit. Objectives. To examine the effects of phospholipase A 2 on the neural response of somatosensory neurons innervating the lumbar facet joint and surrounding tissues. Summary of Background Data. An irritating component of disc tissue may be phospholipase A 2 , which has been found at extraordinarily high levels in herniated and painful discs. Phospholipase A 2 has been shown to be inflammatory, but its effect on nerve response has never been shown. Methods. Surgically isolated facet joint capsules from rabbits were investigated by means of electrophysiologic and histologic techniques. Phospholipase A 2 was injected into the characterized nerve receptive field, and responses were evaluated over time with varying doses. Results. The injection of phospholipase A 2 into the nerve receptive fields produced neurotoxicity with a 1500-U dose, sensitization of the nerves and recruitment of silent units with a 750-U dose, and no electrophysiologic effect with a 400-U dose. The tissues injected with phospholipase A 2 and control solutions were examined histologically using a hematoxylin and eosin staining technique. In all three doses, the inflammatory changes were observed as soon as 2 hours after the injections. In control subjects, no changes were observed. Conclusions. After phospholipase A 2 injection, the discharge rate of the units showed dose and time dependent patterns. Regardless of the different doses, histologic changes were observed as soon as 2 hours after the phospholipase A 2 injections.

As a model system, rabbits are particularly useful in transplantation studies because of their size and accessibility. However, inbred rabbits of known MHC haplotype are not commercially available, and there are few monoclonal antibody reagents available to permit serological typing of experimental animals prior to transplant. Here we present a rapid and reliable method to distinguish rabbits that differ at their MHC class I and class II loci, and present 34 class I and 16 class II haplotypes determined by restriction fragment-length polymorphism analysis of outbred heterozygous rabbits. The applicability of this molecular typing system to transplantation experiments in the New Zealand White rabbit is discussed.

Various materials have been used for reconstruction of both acquired and congenital calvarial defects. Unfortunately, each has its limitations. Autologous bone grafts have irregular rates of resorption that may require secondary corrective surgery, and individual harvest sites have limited stores that can necessitate additional donor locations. Alloplastic materials have unlimited quantities and volume stability but they may not become incorporated and are associated with a higher incidence of infection. The optimal bone substitute should stimulate new bone formation and permanently supplant the temporary space filler, thereby reconstituting the surgical defect. We evaluated 2 newly available bone substitutes, resorbable natural bone mineral (Bio-Oss particles) and a combination of collagen and natural bone mineral collagen combination (Bio-Oss sponges), to repair calvarial defects in an adult, male, New Zealand white rabbit model. We found that the particulate Bio-Oss material resorbed and then underwent the normal physiological stages of bone remodeling. The collagen and Bio-Oss combination was replaced by new bone ingrowth. These materials may have potential for use in the reconstruction of skull defects.

We developed a new animal model to recreate the condition of an open fracture in communication with the maxillary sinus. We then studied wound healing of the sinus wall structures following fracture in the presence of an alloplastic implant. This model is designed to simulate the alloplastic repair of an orbital floor fracture in humans. The New Zealand White rabbit was used as the animal model. Standardized 8-mm defects were made bilaterally in the maxillary sinuses to include bone and mucosa in 21 rabbits. Two different implants were placed in the soft-tissue pockets to obturate the defects, exposing one surface of the implant to the open sinus. Medpor porous polyethylene and silicone implants were compared. Animals were killed at 1, 2, 3, and 4 weeks and at 2, 4, and 5 months after implantation. Gross examination of the specimens for the amount of mucosal closure and implant tissue fixation was performed. Histological sections were evaluated for bone and soft-tissue morphology juxtaposed to the implant. Complete closure of the mucosal defect was demonstrated with both types of implants. Medpor implants showed both vascular and soft-tissue ingrowth into its pores by week 1. Bone ingrowth was seen by week 3. Closure of the Medpor obturated defects occurred more rapidly than in the silicone group (p < 0.004 at week 4). The Medpor implants demonstrated bone and soft-tissue fixation, and mature overlying mucosa was reconstituted over the defects. Silicone implants demonstrated a fibrous tissue reaction within 1 week of implantation and they never became fixed to bone or soft tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of alloxan-induced diabetes on the reactivity of corporeal nerves, endothelium and smooth muscle was studied in the New Zealand white rabbit. Fifteen rabbits were randomly divided into treated (n = 6) and control (n = 9) groups. The treated group was maintained for 6 weeks. Two control groups were studied. One control group (n = 3) was maintained for 6 weeks as littermate controls for diabetic group. The second control group (n = 6) was not maintained but was weight matched with the 6 week diabetic group. The reactivity of corpus cavernosum tissue from the diabetic animals and the control animals was studied in organ chambers. When tissue contraction was produced with phenylephrine for the study of relaxation to various stimuli, the tension induced was similar in the diabetic and the control groups. Relaxation of corpus cavernosum tissue to electrical stimulation of autonomic nerves as well as relaxation to the endothelium-dependent vasodilator acetylcholine were comparably unaffected in the weight matched and littermate control groups while significantly inhibited in the diabetic group. Treatment of the corporeal tissue with the cyclooxygenase inhibitor indomethacin enhanced the relaxation to electrical stimulation and to acetylcholine in the control and in the diabetic groups but did not improve the significant difference in relaxation between the two groups. Relaxation of corporeal tissue to endothelium-independent vasodilators, papaverine and nitroprusside was similar in the control groups and the diabetic groups. It is concluded that diabetes impairs neurogenic and endothelium-mediated relaxation of rabbit corpus cavernosum smooth muscle. These findings are comparable to those described in corpus cavernosum tissue from diabetic men, showing the validity of this experimental animal model. The mechanism for the nerve or endothelial dysfunction does not appear to involve alteration in cyclooxygenase products of arachidonate or the ability of the corporeal smooth muscle to relax via a cGMP-dependent mechanism. Since nitric oxide has been shown to act as the nonadrenergic noncholinergic neurotransmitter as well as endothelium-derived relaxing factor (EDRF) of the trabecular smooth muscle, it is possible that impairment of neurogenic and endothelium-dependent relaxation due to diabetes is mediated by alteration in the synthesis or availability of nitric oxide in corporeal tissue.

Trazodone hydrochloride is an oral antidepressant agent which has been associated with the improvement of erections in impotent men and the development of prolonged erections or priapism in potent men. An in vivo study in animal and human subjects was performed to gain experience with the effect of intracavernosal trazodone. In the anesthetized New Zealand White rabbit, intracavernosal trazodone or its major metabolite m-chlorophenylpiperazine (m-CPP) produced full penile erection in 76% and 84% of animals studied respectively with doses ranging from one to 15 mg. On the other hand, intracavernosal administration of five mg. papaverine resulted in a prolonged erection in 90% of animals studied. In 13 selected volunteer patients, intracavernosal trazodone caused tumescence but not full penile erection with corporal body pressures of 28.2 +/- 5.8 mm. Hg. Intracavernosal papaverine or papaverine and phentolamine in these subjects resulted in significantly higher corporal body pressures of 58 +/- 18 mm. Hg (p less than .05). Intracavernosal administration of alpha adrenoceptor agonists but not normal saline resulted in complete detumescence of trazodone- or m-CPP-induced prolonged erection in the animal studies. Intracavernosal trazodone results in erectile activity that appears in part based on its local alpha blocking activity but like other intracavernosal alpha-blocking agents is not as effective in initiating penile erections as are intracavernosal agents that directly induce smooth muscle relaxation.

PURPOSE The Baerveldt glaucoma implant is an aqueous shunting device with large surface area that is installed through a single-quadrant conjunctival incision. A rabbit model of the Baerveldt implant was created to obtain serial histology and clinical information over 1 year. METHODS Modified versions of the Baerveldt implant (110 or 160 mm2) were implanted in 18 normal New Zealand white rabbit eyes. The rabbits were examined periodically and their intraocular pressures (IOPs) recorded. They were killed at monthly intervals to obtain histology of the bleb capsules. RESULTS Thin capsules were present at 1 month, which consisted of lamellar collagen deposition surrounded by a granulomatous reaction with multinucleate giant cells. Inflammatory cells (probably macrophages) were scattered on the inner bleb surface. The granulomatous reaction resolved after 4 months. Subsequently, capsule thickness and cellularity remained relatively stable, although the collagen stroma became less compact over time. Sixteen rabbit eyes had initial IOP reductions of > or = 3 mm Hg compared with fellow eyes, which persisted up to 4 weeks postoperatively. Seven eyes (39%) exhibited a hypertensive phase (IOP exceeded that of fellow eye by > or = 3 mm Hg) from 2 weeks to 3 months postoperatively. CONCLUSION The Baerveldt explant is surrounded by a fibrous capsule that matures over time. The bleb histology in the rabbit model is similar to that described with the Molteno implant in primates and humans, except for the eventual development of a fibroblastic inner lining in the rabbit model. This contrasts with primate and human models, in which the inner lining remains an open mesh.

The purpose of this study was to determine the optimal method of stimulating multiple motor points in a muscle in an attempt to improve fatigue resistance. The long head of triceps, which has 2 to 3 motor points, in an adult New Zealand white rabbit was used as the muscle model. The fatigue index, defined as the percentage of maximum force at time t, was compared during the fatigue tests. Five test groups were defined based on the stimulation pattern of the muscle : (1) Group Al : The proximal motor point was stimulated at 20 Hz ; (2) Group A2 : The distal motor point was stimulated at 20 Hz ; (3) Group B : Both motor points were stimulated simultaneously at 20 Hz ; (4) Group C : Both proximal and distal motor points were stimulated at alternate intervals of 10 seconds at 20 Hz ; and (5) Group D : Both motor points were stimulated sequentially at 10 Hz. Each test was conducted for 6 minutes. In sequential stimulation (Group D), the fatigue index was significantly higher when compared with the other test groups at Minutes 4, 5, and 6. In groups Al, A2, B, and C, there were no significant differences in the fatigue indices. For optimal control of muscle contraction in functional electrical stimulation, electrodes should be inserted into all motor points for a given muscle. Sequential stimulation of these points can improve fatigue resistance.

Indirect skeletal muscle injuries have been found to occur exclusively near the myotendinous junction (MTJ). Although muscle cells are syncytial and extend far into the muscle belly, the response to this injury has been shown to be limited to a focal area near the MTJ. This study examined single muscle fibers near their site of rupture in order to document structural changes that may help to explain this limited injury response. A partial, nondisruptive strain injury was created in a New Zealand white rabbit extensor digitorum longus muscle. The muscles were left in vivo for 60 min or 6 h before harvesting. The specimens were divided into four groups of single fibers: ruptured fibers (60 min) attached to muscle belly (group I); ruptured fibers (60 min) attached to tendon (group II); ruptured fibers (6 h) attached to muscle belly (group III); and normal, unstretched fibers (60 min) at the MTJ (group IV) (N = 10 for each group). Sarcomeres closest to the site of fiber rupture in the three injured groups (I, II, and III) were hypercontracted, with lengths well below the physiologic range (I: 0.86 +/- 0.08 microns, II: 0.96 +/- 0.09 microns, III: 0.96 +/- 0.21 microns). There was a progressive increase in sarcomere length, which became normal by 300-500 microns away from the site of rupture (I: 2.17 +/- 0.48 microns, II: 2.69 +/- 0.42 microns, III: 2.08 +/- 0.48 microns). The 6-h fibers in group III showed evidence of necrosis before the transition to normal sarcomere spacing occurred.(ABSTRACT TRUNCATED AT 250 WORDS)

The vascular repair of a lower tibial transverse osteotomy in the New Zealand white rabbit held in an external fixator was studied in three groups. In the first group, composed of 18 animals, the osteotomy gap was maintained throughout repair. Three animals were killed every two weeks up to 12 weeks postoperatively. In the second group, composed of three animals killed at six weeks, the fragments were brought into contact. In a third and similar group, the osteotomy was compressed. Plain roentgenograms were taken weekly, and intraarterial perfusion with Micropaque was performed when the animals were killed. Roentgenography using fine-grain film, microradiography, and histology were carried out on a midsagittal tibial slice. The results showed that following transverse osteotomy in which the gap was maintained, vascular union of the proximal and distal cortices and associated external callus masses had usually occurred by ten weeks postoperatively. However, an occasional hypovascular zone at the osteotomy site at 12 weeks was associated with fibrous delayed union. In contrast, when apposition or compression of the fragments was used, repair was accelerated, and cortical bone union was established at six weeks. Vascular union of the fragments occurred predominantly through the medullary vessels. The results emphasize the overriding clinical importance of abolition of a fracture gap to achieve rapid revascularization of a fracture and its union by bone.

Halothane is commonly viewed as a more potent cerebral vasodilator than isoflurane. It was speculated that the lesser vasodilation caused by isoflurane might be the result of the greater reduction in cerebral metabolic rate (CMR) that it causes, and that the relative vasodilating potencies of halothane and isoflurane would be similar if the two agents were administered in a situation that precluded volatile-agent-induced depression of CMR. To test this hypothesis, cerebral blood flow (CBF) and the cerebral metabolic rate for oxygen (CMR01) were measured in two groups of rabbits before and after the administration of 0.75 MAC halothane or isoflurane. One group received a background anesthetic of morphine and N2O, which resulted in an initial CMR01 of 3.21 ± 0.17 (SEM) ml · 100 g−1 · min−1; second group received a background anesthetic of high-dose pentobarbital, which resulted in an initial CMR01 of 1.76 ± 0.16 ml · 100 g−1 · min−1. In rabbits receiving a background of morphine sulfate/ N2O, halothane resulted in a significantly greater CBF (65 ± 10 ml · 100 g−1 · min−1) than did isoflurane (40 ± 5 ml · 100 g−1 · min−1). Both agents caused a reduction in CMRO1, but CMRO1 was significantly less during isoflurane administration. By contrast, with a background of pentobarbital anesthesia, CBF increased by significant and similar amounts with both halothane and isoflurane. With halothane, CBF increased from 22 ± 2 ml · 100 g−1 · min−1 in the control state to 39 ± 3, and with isoflurane from 24 ± 2 to 38 ± 2 ml · 100 g−1 · min−1. CMR01 was not depressed further by either halothane or isoflurane. These results suggest that the relative effects of halothane and isoflurane on CBF are dependent on the CMR present prior to their administration. When the preexistent CMR is not markedly depressed, isoflurane decreases CMR and causes less cerebral vasodilation than does halothane. When initial CMR is depressed, halothane and isoflurane have similar vasodilating potencies.

The growth of vascularized onlay bone (autogenous) transfers on the skulls of 27 newborn New Zealand white rabbits was studied. Freeze-dried bone weight in control newborns and control adults (group 1) was compared with that in experimental adult animals (group 2). In the experimental group, the bone was transferred on the auricularis anterior muscle and neurovascular pedicle. The flap was deliberately maintained without osseous contact or functional-myogenic stress. The myoosseous bone transfers (group 2) exhibited statistically significant osseous enlargement when compared with the control newborns (p = 0.006); however, the weights were significantly less than those of the adult matched controls (group 1, p less than 0.001). Representative histological sections were also studied. Skeletal unit growth of a portion of the New Zealand white rabbit's skull was achieved despite marked alteration in the "functional matrix." The study demonstrated that vascular supply is the other independent factor affecting bone growth. Generally neglected as a variable in the literature of the subject, vascular supply should be considered within the functional matrix concept of craniofacial growth.

The rationale for the design of surgical models of microvascular thrombosis is discussed, and a new model, the arterial inversion graft (AIG), is described and evaluated in the New Zealand white rabbit. Femoral artery segments of predetermined length are excised, gently turned inside-out, and resutured into their native position. Blood flow is restored, and at varying time intervals, vessel patency is assessed through the direct "milking test." In this study, three groups of 20 arterial inversion grafts of 2, 5, and 10 mm in length are created and evaluated for patency at 1 hour and again at 7 days. The incidence of femoral artery occlusion in this model appears to be an increasing function of arterial inversion graft length both at 1 hour--30 percent (2 mm), 80 percent (5 mm), and 100 percent (10 mm)--and at 7 days--65 percent (2 mm), 90 percent (5 mm), and 100 percent (10 mm). This proportionality suggests the arterial inversion graft may be adjusted in length to provide an incidence of vessel occlusion best suited to the needs of any particular experiment.

An animal model of partial hepatic artery occlusion and radiofrequency (RF)-induced hepatic hyperthermia was developed in the New Zealand white rabbit. Seventy-seven percent (10/13) of animals survived partial hepatic artery occlusion, 82% (41/50) survived RF-induced hepatic hyperthermia, and 66% (24/36) survived combined occlusion-hyperthermia. Mesenteric infarction secondary to inadvertent embolization of intestinal arteries was the principal cause of death in animals undergoing partial hepatic artery occlusion. Extrahepatic thermal toxicity appeared to be the major cause of death in animals subjected to hepatic hyperthermia or occlusion hyperthermia although some animals showed evidence of hepatic necrosis as well. Recent developments in our laboratory hold the promise that extrahepatic thermal toxicity can be eliminated by selectively focusing heat into the liver allowing exploration of the efficacy of occlusion-hyperthermia in controlling VX-2 tumors implanted in the rabbit liver.

MAC determinations for halothane, enflurane, and isoflurane were performed in New Zealand white rabbits (n = 8, approximate age 6 months). The MAC values (+/-SD) were as follows: halothane 1.39 +/- 0.23%, enflurane 2.86 +/- 0.18%, and isoflurane 2.05 +/- 0.18%. Comparison of these results with published MAC values for other species suggests that the ratio of the potencies for any pairing of these three agents is constant from species to species. This observation provides a means for assessing the validity of preexisting or newly determined MAC values.

The effect of nitrous oxide on cortical cerebral blood flow (CBF) was examined during a varying background anesthetic state in the New Zealand White rabbit. Seventy percent nitrous oxide resulted in significant and similar increases in CBF during anesthesia with both 0.5 MAC of halothane (44 +/- 14 to 63 +/- 17 ml.100 g-1.min-1) (mean +/- SD) and anesthesia with isoflurane (34 +/- 9 to 41 +/- 11 ml.100 g-1.min-1). During anesthesia with 1.0 MAC halothane or isoflurane, N2O also increased CBF, but the increments (halothane, 73 +/- 34 to 111 +/- 54 ml.100 g-1 min-1; isoflurane 34 +/- 13 to 69 +/- 34 ml.100 g-1.min-1) were significantly greater than those observed at 0.5 MAC. When 0.5 MAC halothane or isoflurane was supplemented with morphine (10 mg/kg followed by an infusion of 2 mg.kg-1.min-1), the CBF effect of N2O was not significantly different from that observed with 0.5 MAC alone. It was concluded that, in the rabbit, the effects of N2O on cortical CBF vary with the background anesthetic state and that the increase in CBF caused by N2O becomes greater as the end-tidal concentration of halothane or isoflurane increases from 0.5 to 1.0 MAC. Morphine, when added to 0.5 MAC of halothane or isoflurane, does not alter the effect of 70% N2O on cortical CBF.

The effect of external skeletal fixation on blood supply and healing of the tibia was investigated in the New Zealand white rabbit. Bilateral osteotomies were made in ten rabbits. One osteotomy was stabilized with a small unilateral external fixator and the other with a conventional long-leg cast. The animals were killed at various intervals from one to ten weeks. Microsphere infusions indicated a greater blood supply in the cast-treated osteotomies after five weeks. Histologic examination showed that external fixation alters the proportions of periosteal and medullary ossification in the healing process. External fixation decreased the periosteal response but seemed to enhance both the endochondral ossification of callus and medullary ossification.