Advances in Regional Vascular Injection Techniques for the Delivery of Stem Cells to Musculoskeletal Injury Sites.

Vascular injections of stem cells are a pertinent alternative to direct intralesional injections when treating multiple or extensive lesions or with lesions impossible to reach directly. Extensive research using stem cell tracking has shown that intra-arterial injections without the use of a tourniquet should be preferred over venous or arterial regional limb perfusion techniques using a tourniquet. The median artery is used for the front limbs and the cranial tibial artery for the hind limbs. Proper efficacy studies are still lacking but early clinical work seems promising.

Pilot study comparing serum chemotherapy levels after intra-arterial and intravenous administration in dogs with naturally occurring urinary tract tumors.

The proposed advantages of intra-arterial chemotherapy (IAC) are based on the premises of local dose escalation to the tumor and reduced availability of systemic drugs. There is a lack of objective pharmacokinetic data to confirm the advantage of IAC in dogs with naturally occurring urogenital tumors. The objective of this study was to determine if IAC administration in urogenital tumors would result in decreased systemic drug exposure when compared to intravenous routes. Twenty-two dogs with naturally occurring urogenital tumors were enrolled in this prospective case-controlled study. Mitoxantrone, doxorubicin, or carboplatin were administered by IAC and intravenous routes [intravenous awake (intravenous chemotherapy - IVC) and under general anesthesia (IVGAC)] 3 weeks apart. Serum assays were used to determine the extent of systemic drug exposure. Dose-normalized peak systemic serum concentration (Cmax) and area under the serum drug concentration-time curve (AUC) were used to quantify systemic exposure. A total of 26 mitoxantrone treatments were administered to 10 dogs. While there was no significant difference in Cmax, the AUC was significantly lower after IAC compared with IVGAC. Ten doxorubicin treatments were administered to 5 dogs. There were no significant differences in Cmax or AUC. A total of 14 carboplatin treatments were administered to 7 dogs. The Cmax was significantly lower for IAC compared to IVC, while the AUC values were equivocal. This study demonstrates certain lower serum values may be achieved after IAC delivery of carboplatin and mitoxantrone. These chemotherapy agents may have a preferred pharmacological profile for regional chemotherapy delivery in dogs with urogenital tumors.

Les avantages proposés de la chimiothérapie intra-artérielle (CIA) sont basés sur les prémisses d'une escalade de la dose locale à la tumeur et d'une disponibilité réduite des drogues systémiques. Il y a un manque de données pharmacocinétiques objectives pour confirmer l'avantage de l'administration de CIA chez les chiens avec des tumeurs urogénitales se produisant naturellement. L'objectif de la présente étude était de déterminer si l'administration de CIA lors de tumeurs urogénitales résulterait en une diminution de l'exposition systémique aux drogues lorsque comparé aux voies intraveineuses. Vingt-deux chiens avec des tumeurs urogénitales d'occurrence naturelle participèrent à cette étude cas-témoin prospective. De la mitoxantrone, de la doxorubicine, ou de la carboplatine furent administrées par CIA et voies intraveineuses [intraveineuse éveillée (chimiothérapie intraveineuse ­ CIV) et sous anesthésie générale (CIVAG)] à 3 sem d'intervalle. Des analyses du sérum furent utilisées afin de déterminer l'étendue de l'exposition systémique aux drogues. Le pic de la concentration sérique systémique normalisé pour la dose (Cmax) et la surface sous la courbe de la concentration sérique de la drogue-temps (SSC) furent utilisés pour quantifier l'exposition systémique. Un total de 26 traitements à la mitoxantrone fut administré à 10 chiens. Bien qu'il n'y ait pas de différence significative dans le Cmax, la SSC était significativement plus basse après la CIA comparativement à la CIVAG. Dix traitements de doxorubicine furent administrés à cinq chiens. Il n'y avait pas de différence significative dans le Cmax ou ls SSC. Un total de 14 traitements de carboplatine fut administré à sept chiens. Le Cmax était significativement plus bas pour la CIA comparativement à la CIV, alors que les valeurs de SSC étaient équivoques. Cette étude démontre que certaines valeurs sériques plus faibles peuvent être obtenues après CIA avec la carboplatine et la mitoxantrone. Ces agents de chimiothérapie pourraient avoir un profil pharmacologique préférentiel pour livraison régionale de chimiothérapie chez les chiens avec des tumeurs urogénitales.(Traduit par Docteur Serge Messier).

Scintigraphic Tracking of Allogeneic Mesenchymal Stem Cells in the Distal Limb After Intra-Arterial Injection in Standing Horses.

OBJECTIVE: To assess the feasibility of intra-arterial administration of allogeneic mesenchymal stem cells (MSC) in the median artery of standing horses and evaluate the distribution and retention of radiolabeled cells. STUDY DESIGN: In vivo experimental study. ANIMALS: Six research horses. METHODS: Technetium(99m) -HexaMethyl-Propylene-Amine Oxime-labeled MSC were injected under ultrasound guidance in the median artery of 6 front limbs of 3 horses, standing under sedation. Scintigraphic images were obtained at the time of injection, and at 1, 6, and 24 hours postinjection. Six additional limbs from 3 horses were similarly injected with unlabeled MSC. Ultrasound was performed the following day for assessment of vascular changes. RESULTS: Intra-arterial injection was performed successfully in 11 of 12 limbs. In 1 limb, partial periarterial injection compromised the success of the procedure. Homogeneous distribution of radiolabeled MSC was observed through the entire distal limb, including within the hoof. Partial venous thrombosis was found in both groups of horses, but was subjectively less severe in horses injected with unlabeled MSC. No lameness was observed. Transient swelling of the distal limb occurred in only 1 limb. CONCLUSION: Intra-arterial injection of MSC can be performed in standing horses under sedation and successfully distribute MSC to the distal limb. A risk of periarterial injection was identified but can be reduced with proper sedation, local anesthesia, and increased experience. Partial venous thrombosis was observed as a complication, but did not cause changes of clinical importance, other than rare transient swelling.

FEASIBILITY AND SAFETY OF CONTRAST-ENHANCED ULTRASOUND IN THE DISTAL LIMB OF SIX HORSES.

Vascular alterations play important roles in many orthopedic diseases such as osteoarthritis, tendonitis, and synovitis in both human and equine athletes. Understanding these alterations could enhance diagnosis, prognosis, and treatment. Contrast-enhanced ultrasound (CEUS) could be a valuable method for evaluation of blood flow and perfusion of these processes in the equine distal limb, however no reports were found describing feasibility or safety of the technique. The goal of this prospective, experimental study was to describe the feasibility and safety of distal limb CEUS in a sample of six horses. For each horse, CEUS of the distal limb was performed after intravenous injections of 5 and 10 ml, as well as intra-arterial injections of 0.5 and 1 ml contrast medium. Vital parameters were monitored and CEUS images were assessed qualitatively and quantitatively for degree of contrast enhancement. None of the horses had clinically significant changes in their vital parameters after contrast medium injection. One horse had a transient increase in respiratory rate, and several horses had mild increases of systolic blood pressure of short duration after intravenous, but not after intra-arterial injections. Intra-arterial injection was possible in all horses and resulted in significantly improved contrast enhancement both quantitatively (P = 0.027) and qualitatively (P = 0.019). Findings from this study indicated that CEUS is a feasible and safe diagnostic test for evaluation of the equine distal limb. Future studies are needed to assess the clinical utility of this test for horses with musculoskeletal diseases.

Ultrasound-guided injection of the median artery in the standing sedated horse.

REASONS FOR PERFORMING STUDY: Injection of the median artery of horses leads to better distribution and persistence of mesenchymal stem cells than i.v. regional limb perfusion. Due to technical difficulties, intra-arterial injections thus far have only been performed under general anaesthesia. OBJECTIVES: To assess the feasibility of injection of the median artery in standing sedated horses. STUDY DESIGN: Experimental study. METHODS: Six horses were included in the study. After median and ulnar regional analgesia, radiographic contrast material was injected in the median artery of both front limbs, using a catheter in one limb and a direct needle injection in the other. Ultrasound guidance was used for catheter and needle placement. Radiographs were obtained for confirmation of successful injection. Post procedural ultrasound examination was performed to assess vascular compromise. RESULTS: Catheter placement was successful in all 6 limbs, but in one limb injection was not possible due to arterial spasm. Movement of the limbs after the initial injection resulted in loss of functionality of the catheter in 2 other horses. Direct needle injection was successful on all 6 limbs, with periarterial extravasation observed in 2 limbs. No clinical complications were observed. CONCLUSIONS: Injection of the median artery can be performed in standing horses under sedation. Direct needle injection is a more practical technique than catheterisation, as it is easier to perform and less likely to induce arterial spasm. Periarterial extravasation remains a possible limitation of the technique. Intra-arterial injections may be useful for administration of therapeutic agents such as mesenchymal stem cells on standing sedated horses.

Administración intrarterial de un magnetofluido termoterapéutico en un modelo experimental de metástasis hepáticas. Estudio de distribución con resonancia magnética y espectrometría / Magnetic resonance imaging and spectrometric study of the distribution of thermotherapeutic magnetofluid after intra-arterial administration in an experimental model of liver metastases

Objetivo. Valorar la distribución vascular de un magnetofluido por técnicas de imagen y laboratorio, en un modelo de metástasis hepáticas. Material y métodos. El hígado de 33 ratas WAG/RijCrl fue diseminado con células de carcinoma colorrectal CC-531. Tras comprobar desarrollo tumoral, diez ratas recibieron infusiones intrarteriales hepáticas de Lipiodol® con nanopartículas de Fe3O4 en suspensión, y cinco se reservaron como controles. Posteriormente, en RM de 1,5 T se practicaron secuencias axiales STIR (TR: 3.600ms/TE: 29ms/TI: 130ms) y eco de gradiente (EG) (120/4 y 120/14). Tras necropsia, según desarrollo tumoral, las ratas se clasificaron en dos estadios: precoz (< 10 metástasis, de < 3mm), avanzado (> 10 metástasis, de>3mm). De los 15 animales se tomaron muestras de hígado y metástasis, para cuantificar mediante espectrometría (ICP-MS) las concentraciones de hierro. En el análisis estadístico se emplearon pruebas no paramétricas. Se consideraron significativos valores de p < 0,05. Resultados. Cinco animales presentaron afectación precoz y cinco, avanzada. En secuencias EG, las metástasis en estadio precoz mostraron disminución homogénea de señal atribuible a presencia de magnetofluido. La espectrometría demostró diferencias significativas entre la concentración de hierro determinado en metástasis de ratas en estadio precoz y control (p=0,002), y entre animales en estadio precoz y avanzado (p=0,001). La razón entre hierro exógeno metastásico y hepático en ratas en estadio precoz fue 2,6:1. La concentración de hierro exógeno hepático y tumoral mostró diferencias significativas sólo en animales en estadio precoz (p=0,043). Conclusiones. RM y Espectrometría permitieron evaluar la distribución vascular hepática del magnetofluido, y revelaron su desigual afinidad por metástasis en diferentes estadios (AU)

Objective. To use imaging and laboratory techniques to evaluate the vascular distribution of magnetofluid in a rat model of liver metastases. Material and methods. The livers of 33 WAG/Rij Crl rats were seeded with CC-531 colorectal cancer cells. After we checked tumor development, 10 rats received hepatic intra-arterial infusions of Lipiodol® with nanoparticles of Fe3O4 in suspension, and 5 were reserved as controls. Axial STIR (TR: 3,600ms/TE: 29ms/TI: 130ms) and gradient-echo (GE) (120/4 and 120/14) MRI sequences were acquired on a 1.5 T scanner. After necropsy, rats were classified into one of two stages according to tumor development: early (< 10 metastases, each < 3mm) or advanced (> 10 metastases, each > 3mm). Samples of liver and of metastases were taken from the 15 animals for quantification of iron concentrations by inductively coupled plasma mass spectrometry (ICP-MS). The data were analyzed using nonparametric tests; values of p < 0.05 were considered significant. Results. Five animals had early tumor development and five had advanced tumor development. In the GE sequences, early stage metastases showed homogeneous signal reduction attributable to the presence of magnetofluid. Spectrometry found significant differences between the iron concentration in rats with early stage metastases and controls (p=0.002) as well as between rats with early stage metastases and those with late stage metastases (p=0.001). The ratio of exogenous iron in metastases and in liver in early stage rats was 2.6:1. The concentration of exogenous iron in the liver was significantly different from that in tumors only in early stage animals (p=0.043). Conclusions. MRI and spectrometry made it possible to evaluate the vascular distribution of magnetofluid in the liver and revealed the differences in its affinity for metastases in different stages of disease (AU)

Novel microcatheters for selective intra-arterial injection of fluid in the rat brain.

BACKGROUND AND PURPOSE: The internal carotid artery (ICA) in the rat has a single extracranial branch, which supplies the muscles of mastication. The rat ICA also has multiple intracranial branches including (from proximal to distal): multiple small perforating arteries which supply the hypothalamus and the anterior choroidal artery which supplies the choroid plexus and part of the basal ganglia. At the ICA terminus, the vessel bifurcates into the anterior and middle cerebral arteries. The purpose of this study was to demonstrate selective injection of ICA branches in the rat. MATERIALS AND METHODS: Microcatheters (mucath1 and mucath2) were fabricated by plugging the tip of 169-mum outer diameter polyimide tubing and perforating the sidewalls. A 450-mum polydimethyl-siloxane cylinder was affixed to the distal tip of mucath2 but not mucath1. We evaluated the territory of mucath1 injection ex vivo using magnetization-prepared rapid acquisition of gradient echo MR imaging of brain specimens injected at necropsy. Territories of mucath1 and mucath2 injection were evaluated in vivo with dynamic susceptibility-weighted contrast-enhanced MR imaging. The territory of mucath2 also was evaluated in vivo with fused static microPET/T1 MR images performed after [(18)F] fluorodeoxyglucose ((18)FDG) injection. We evaluated additional catheterized and injected animals at 48 hours using physical examination, T2 MR images, and postmortem brain histologic specimens. RESULTS: Gadolinium-diethylene-triamine pentaacetic acid (Gd-DTPA) and (18)FDG injected through mucath1 selectively opacified the ipsilateral cerebral hemisphere, with no contralateral opacification. Gd-DTPA injected through mucath2 selectively opacified the territories of the hypothalamic perforating arteries, and anterior choroidal artery. There was no iatrogenic complication 48 hours after 20- to 25-minute injections performed with mucath1 or mucath2. CONCLUSIONS: We have developed 2 microcatheters which can be placed in the ICA for selective injection of its branches. One microcatheter selectively injects the ipsilateral cerebral hemisphere. The other selectively injects only the hypothalamus and lateral thalamus.

Cerebral injury from intracarotid injection in an alpaca (Vicugna pacos).

A mixture of ketamine, xylazine, and butorphanol was inadvertently injected into the right carotid artery of a 1-year-old alpaca. Injection was followed by a brief period of recumbency and seizure activity. The alpaca recovered, but was euthanatized 72 hr later because of development of progressive neurologic deficits. Pathologic findings were confined to the right cerebrum, meninges, thalamus, and hippocampus. Cerebrocortical edema with astrocytic reaction, perivascular hemorrhage and neutrophilic infiltration, and fibrinoid necrosis of vasculature within the meninges and thalamus were the most prominent lesions. Neuronal necrosis was mild. Astrocytic reaction within the right cerebral cortex was confirmed with immunohistochemistry for glial fibrillary acidic protein.

Study on cranial and caudal mesenteric arteries in opossum (Didelphis albiventris) / Estudio de las arterias mesentéricas craneal y caudal del zorrillo (Didelphis albiventris)

The objective of this study is to describe the cranial and caudal mesenteric arteries in 10 opossuns after Neoprene latex injection. The cranial mesenteric artery arises from the abdominal aorta, caudally to the celiac trunk, originating the caudal duodenal pancreatic artery, middle and right colic, jejunal and ileocecocolic arteries. The caudal mesenteric artery arises from the aorta, cranially to the external iliac arteries, originating the cranial rectal and left colic arteries.

El objetivo de este estudio fue describir las arterias mesentéricas craneal y caudal de 10 zorrillos después de la inyección de látex Neoprene. La arteria mesentérica craneal tiene origen en la aorta abdominal, caudalmente al tronco celíaco y da origen a las arterias: pacreáticoduodenal caudal, cólica media derecha, yeyunales e ileocecocólica. La arteria mesentérica caudal con origen en la aorta, cranealmente a las arterias ilíacas externas, da origen a las arterias rectal craneal y cólica izquierda.

Comparison of perioperative analgesic protocols for dogs undergoing tibial plateau leveling osteotomy.

OBJECTIVE: To compare effects of 3 commonly used perioperative analgesic protocols (epidural injection, intra-articular injection, and intravenous [IV] injection) for management of postoperative pain in dogs after tibial plateau leveling osteotomy (TPLO). STUDY DESIGN: Prospective, randomized clinical trial. ANIMALS: Fifty-six healthy dogs with naturally occurring cranial cruciate ligament rupture. METHODS: Dogs were premedicated with IV hydromorphone and acepromazine and were randomly assigned to receive either E (preoperative epidural injection with morphine and bupivacaine), IA (pre- and postoperative intra-articular injections of bupivacaine), or C (neither epidural morphine and bupivacaine, nor intra-articular bupivacaine). All dogs were administered hydromorphone (0.05 mg/kg IV) at extubation and as needed to maintain comfort postoperatively. Patients were observed and monitored continuously for 24 hours and discomfort was assessed using visual analog pain scores (VASs), multifactorial pain scores (MPSs), and response to a pressure nociceptive threshold (PNT) measuring device. Time to 1st dose and the total doses of hydromorphone required to achieve adequate comfort for each dog were recorded. RESULTS: No differences in measured indices of postoperative pain were observed between dogs of each treatment group; VAS (P=.190), MPS (P=.371), and PNT (P=.160). Time to 1st analgesic intervention was longer for Group E compared with Group C (P=.005) and longer for Group IA compared with Group C (P=.032). Although time to 1st intervention between Groups E and IA were longer for Group E, differences were not significant. To provide an adequate level of comfort, more analgesic interventions were administered to dogs in Group C compared with dogs in group E (P=.015). On average, more hydromorphone was administered to Group C compared with Group IA (P=.072) and to Group IA compared with Group E (P=.168), but statistical significance was not reached for these data. CONCLUSIONS: In this study population, significant differences were seen in time to 1st hydromorphone dose between Groups E and IA compared with Group C. As well, more supplemental analgesia was administered to Group C compared with Group E to maintain the same level of postoperative comfort. Although differences between Groups E and IA tended to favor the epidural group, differences were minimal and not statistically significant. CLINICAL RELEVANCE: Our results suggest that regardless of analgesic protocol, measured indices of pain in dogs after TPLO can be minimized if dogs are continuously observed and appropriately supplemented with parenteral opioids. However, the frequency of postoperative opioid dosing can be minimized and may be a factor when contemplating supplementary use of epidural or intra-articular injections as part of a balanced analgesic approach.

Evaluation of two combinations of Domitor, Zoletil 100, and Euthatal to obtain long-term nonrecovery anesthesia in Sprague-Dawley rats.

We sought to evaluate a new protocol designed to maintain long-term, nonrecovery, surgical anesthesia in Sprague-Dawley rats. In the first phase, two groups of rats were anesthetized with two different dose combinations of Domitor (medetomidine) and Zoletil 100 (tiletamine-zolazepam) to investigate their efficacy in induction of anesthesia. One combination comprised Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg, whereas the other comprised Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg. Both combinations effectively induced deep anesthesia and caused no mortality, but the duration of anesthesia differed statistically. In the second phase, we induced anesthesia with both Domitor-Zoletil 100 dose combinations then investigated the possibility of maintaining anesthesia for 5 h by administering Euthatal (pentobarbitone) intra-arterially at 10 mg/kg hourly. Depth of anesthesia, mortality, physiological parameters, blood gas analysis, hematology, clinical chemistry, and postmortem histopathology were recorded. Euthatal provided stable long-term anesthesia with both dose combinations of Domitor-Zoletil 100. Seven of 8 (88%) animals anesthetized with Domitor at 50 microg/kg and Zoletil 100 at 20 mg/kg successfully were maintained under deep anesthesia for 5 h. Higher mortality (36% versus 12%) occurred in group of animals treated with Domitor at 35 microg/kg and Zoletil 100 at 40 mg/kg. This difference may be linked to dose-related respiratory depression, as alterations of arterial gas levels were noted. Our findings suggest that, when long-term nonrecovery anesthesia is required, doses of 50 microg/kg Domitor and 20 mg/kg Zoletil 100 are preferable when given with Euthatal to maintain physiological conditions in animals.

Cardiovascular actions of rattlesnake bradykinin ([Val1,Thr6]bradykinin) in the anesthetized South American rattlesnake Crotalus durissus terrificus.

Incubation of heat-denatured plasma from the rattlesnake Crotalus atrox with trypsin generated a bradykinin (BK) that contained two amino acid substitutions (Arg1 --> Val and Ser6 --> Thr) compared with mammalian BK. Bolus intra-arterial injections of synthetic rattlesnake BK (0.01-10 nmol/kg) into the anesthetized rattlesnake, Crotalus durissus terrificus, produced a pronounced and concentration-dependent increase in systemic vascular conductance (Gsys). This caused a fall in systemic arterial blood pressure (Psys) and an increase in blood flow. Heart rate and stroke volume also increased. This primary response was followed by a significant rise in Psys and pronounced tachycardia (secondary response). Pretreatment with N(G)-nitro-L-arginine methyl ester reduced the NK-induced systemic vasodilatation, indicating that the effect is mediated through increased NO synthesis. The tachycardia associated with the late primary and secondary response to BK was abolished with propranolol and the systemic vasodilatation produced in the primary phase was also significantly attenuated by pretreatment, indicating that the responses are caused, at least in part, by release of cathecholamines and subsequent stimulation of beta-adrenergic receptors. In contrast, the pulmonary circulation was relatively unresponsive to BK.

Effect of injecting collagenase into the uterine artery during a caesarean section on the placental separation of cows induced to calve with dexamethasone.

A caesarean section was performed on 30 cows before normal term and 16 to 20 hours after the induction of parturition with dexamethasone. During the surgical procedure, 20,000 U of bacterial collagenase was injected into the uterine artery of 15 of the cows. The average periods of retention of the fetal membranes were 40 hours in the treated cows and 114 hours in the control cows (P<0.001). At 36 hours after the surgery six of the treated cows (40 per cent) but all 15 of the control cows had retained fetal membranes. The collagenase-treated cows showed no abnormal clinical signs during the 10 days after the operation.

Review: reticuloruminal motility--a pharmacological target with a difference?

The vagal sensory inputs to and motor outputs from the hindbrain gastric centres required for reticuloruminal motility were sampled directly in anaesthetized sheep using electrophysiological 'single fibre' techniques and indirectly in conscious, surgically prepared sheep. Drugs were administered by close-arterial injection into a carotid artery to observe central effects and into the coeliac artery to observe peripheral effects on the reticulorumen. Escherichia coli lipopolysaccharide produced intermediates responsible for the smooth muscle relaxation in the first phase of reticuloruminal stasis and for gastric centre depression in the second phase. Adrenergic influences on reticuloruminal motility comprise (a) an alpha1 adrenoreceptor-induced contracture and raised tension receptor sensitivity, (b) an alpha2 adrenoreceptor-mediated depression of the gastric centres causing stasis, excitation of epithelial receptors evoking rumination, and interference with acetylcholine release in the parasympathetic pathway, (c) abeta1 adrenoreceptor-mediated inhibition of the gastric centres, and (d) abeta2 adrenoreceptor-mediated inhibition of intrinsic and extrinsic motility.

Injection technique and scanning electron microscopic study of the arterial pattern of the 20 gestation days (G20) rat fetus.

A technique to obtain microvascular corrosion casts of the G20 rat fetus and the normal pattern of the main arteries of the G20 rat fetus are described. The casts were studied by means of scanning electron microscopy (SEM). The arterial pattern is similar to that described in the adult; however, several variations have been found. It is concluded that the use of vascular corrosion casts studied by SEM may be particularly helpful to observe the extremely small arteries of rat fetuses. Moreover, we suggest that this technique may be useful in practical teratological studies.

Disposition of enrofloxacin (Baytril) into the udder after intravenous and intra-arterial injections into dairy cows.

Enrofloxacin (Baytril) was injected into arteries supplying the udder of dairy cows. The idea was to avoid primary distribution, metabolism and elimination and thus to deliver the drug to the target organ at higher concentration. Enrofloxacin injected into the abdominal aorta or the external iliac artery resulted in high initial enrofloxacin retention by the udder and high milk concentrations. Injection of enrofloxacin into the abdominal aorta resulted in 2.2 times higher milk peak concentration of the drug than intravenous injection into the jugular vein. Injection of the drug into one of the two external iliac arteries allowed drug concentrations of milk from the udder halves to be compared: when enrofloxacin was injected into the right external iliac artery, the peak milk enrofloxacin concentration from the right udder half was 4.8 times that of the left udder half. The bulk of enrofloxacin was absorbed from the milk compartment of the udder before the next regular milking 6.5 h later. By this time, the metabolite ciprofloxacin had accumulated in milk. Pharmacokinetic values for enrofloxacin and its metabolite ciprofloxacin are given separately for serum and milk whey following three intravascular dosing routes.

The effects of intracoeliac injections of alpha-adrenergic agonists and veratridine on reticuloruminal motility and the evocation of rumination in sheep.

The ability of alpha-2 adrenoreceptor agonists and veratridine to evoke rumination and to modify reticular motility in adult Suffolk-cross sheep when injected by close-arterial injection into the forestomach was investigated. The specific alpha-2 adrenoreceptor agonists, xylazine and medetomidine, evoked rumination and increased reticular motility. The Na+ channel activator veratridine also evoked rumination and dramatically increased reticular motility. In contrast, injection of the alpha-1 adrenoreceptor agonist, phenylephrine, was ineffectual in evoking rumination and resulted in reduced reticular motility. It is concluded that the evocation of rumination by alpha-2 adrenergic agonists and veratridine is probably due to the activation of sensory nervous receptors (epithelial receptors) located in the reticulorumen.

Successful treatment of retained placenta with umbilical cord injections of collagenase in cows.

Fetal membranes usually are released from the uterus between 2 and 6 postpartum hours. However, in a substantial percentage of cows (11%), fetal membranes are retained for several days. In part, failure of collagen breakdown seems to be related to retention of fetal membranes. Injections of 200,000 U of bacterial collagenase in 1,000 ml of physiologic saline solution via umbilical arteries (1 or 2) between 24 and 72 hours of retention caused release of retained fetal membranes in 23 of 27 cows (85%) with noninduced retained fetal membranes and in 10 of 14 cows (71%) with experimentally induced retained fetal membranes, within 36 hours after injection. Controls (n = 36) did not release retained fetal membranes within this time. Injections of collagenase via a jugular vein (2.2 x 10(6) U in 1,000 ml of physiologic saline solution), administered over a 30-minute period, caused release of retained fetal membranes within 36 hours in 3 of 6 cows with experimentally induced retained fetal membranes. Clinical complications did not follow treatments with collagenase. Umbilical injections of bacterial collagenase were highly effective in the treatment of retained fetal membranes in cows. The procedure is simple, safe, affordable, and can be completed in 25 minutes.

Intra-arterial cisplatin with or without radiation in limb-sparing for canine osteosarcoma.

METHODS: Forty-nine dogs with spontaneously occurring osteosarcoma underwent limb-sparing surgery after preoperative therapy consisting of intra-arterial cisplatin alone or intra-arterial cisplatin in combination with doses of radiation from 20-40 Gy in 10 fractions. All resections were marginal, and the defect was repaired with a cortical allograft. RESULTS: Local tumor control was strongly influenced by the percent necrosis in the excised specimen. Overall, the estimated 1-year local recurrence rate was approximately 32% (by life-table estimate). Dogs with less than 75% necrosis had an estimated 1-year recurrence rate of 65%; those with greater than 75% necrosis had an estimated 1-year recurrence rate of 15% (P = 0.004, by log-rank test). Local recurrence was influenced by the radiation dose. Dogs receiving 28 Gy or less had an estimated 50% 1-year recurrence rate, and those receiving 32 Gy or more had an estimated 8% 1-year recurrence rate (P = 0.03, by log-rank test). Normal host bone more frequently became necrotic at doses of 36 Gy or more. CONCLUSIONS: Intra-arterial cisplatin in combination with moderate doses of radiation (32 Gy) can achieve a high percent tumor necrosis while maintaining host bone viability. Survival was limited by distant metastasis but was lengthened by treatment compared with some earlier findings.

[The arthrographic presentation of the hip, knee and tarsal joints of the cat]. / Beitrag zur arthrographischen Darstellung von Hüft-, Knie- und Tarsalgelenk der Katze.

The purpose of the present paper was to find out the most suitable localizations to puncture of hip, stifle and hock joints of the domestic cat. These joints are arthrographically presented. Further six contrast mediums in normal commercial usage were tested with regard to there contrast intensity. The only recommendable localization to arthrocentesis of the hip joint is at the cranial border of the greater trochanter of the femur. The stifle joint is approachable either at the medial or lateral border of the Lig. patellae. To puncture the proximal row of the hock joint the recommendable puncture site was found distal of the lateral malleolus between the tendons of the lateral digital extensor muscle and m. extensor digitorum longus. Any arthrocentesis of the distal row of the hock joint isn't recommendable. Contrast mediums with a iodine concentration below 300 mg/ml were not sufficient for arthrography.