4,795,475 A 1/1989 Walker ............................ 623,66 4,814,470 A 3, 1989 Colin et al. .... ... 514,449 4,857,653 A 8, 1989 Colin et al. .... 549/511 4.942,184 A 7, 1990 Haugwitz et al. ............... 51/449 5,002.583 A 3/1991 Pitaru et al. ..................... 623,66 5,059,699 A 10/1991 Kingston et al. 549/511 5,200,534 A 4, 1993 Rao .................... 549/510 5,202,448 A 4/1993 Carver et al. .. 549/510 5,213,580 A 5/1993 Slepian et al. .................... 623, 1 (Continued)

The objective of this study was to investigate the short-term cardiovascular effects of intravenous (IV) medetomidine-midazolam-fentanyl (MMF) injections in the rabbit using vascular ultrasonography and echocardiography.Anesthesia with MMF was induced intramuscularly (IM) in 8 female New Zealand White rabbits before 3 defined bolus injections of MMF were given IV. Before and for 10 min after each MMF injection the following vascular variables [at the left common carotid artery (ACC) after the first injection and at the abdominal aorta (AA) after the second injection]: vessel diameter (D), peak systolic, minimum diastolic, end-diastolic and average blood flow velocities (psBFV, mdBFV, edBFV, Vave), average volumetric flow (VFave), resistance index (RI) and pulsatility index (PI) and other clinical variables: mean arterial pressure (MAP), heart rate (HR), peripheral arterial oxygen saturation and end-tidal CO₂ were recorded. Echocardiography was used after the third injection to investigate changes in cardiac parameters. Additionally, hemodynamic effects were observed at the ACC after complete subcutaneous antagonism of anesthesia by atipamezole-flumazenil-naloxone (AFN) until recovery of the animals.Medetomidine-midazolam-fentanyl IV caused a significant decrease of blood flow velocity in both investigated vessels which was associated with a significant decrease of HR and cardiac performance indicated by the decrease of FS and average volumetric blood flow. Mean arterial pressure significantly increased after each MMF injection; whereas, it significantly decreased after AFN injection. Therefore, MMF and AFN should be carefully used in rabbits and may not be suitable in patients with ventricular dysfunction.

The direct effects of ketamine-xylazine (KET-XYL) on vascular function have not been investigated in rabbits. The short-term cardiovascular effects of intravenous (IV) KET-XYL bolus injection, therefore, should be investigated using vascular ultrasonography.In this prospective experimental study, KET-XYL anesthesia was induced IV in 9 female New Zealand White rabbits before 3 defined test bolus injections of KET-XYL were given IV. Before and for 10 min after each KET-XYL injection vascular and hemodynamic variables were recorded at the left common carotid artery (ACC) after the 1st injection, and at the abdominal aorta (AA) after the 2nd injection. Echocardiography was performed after the 3rd injection to investigate changes in cardiac parameters.Ketamine-xylazine IV caused a significant increase in vessel diameter at the ACC and AA. Average volumetric flow significantly decreased at the ACC and pulsatility index significantly decreased at the AA. Fractional shortening (FS) and heart rate significantly decreased, while mean arterial blood pressure initially increased.Bolus injections of KET-XYL IV produced a transient vasodilatation at the ACC and AA. Despite central vasodilatation, bradycardia, and decrease of FS and average volumetric flow (VFave), mean arterial blood pressure did not significantly decrease indicating well-preserved cardiovascular compensatory mechanism after the ratio and doses of KET-XYL IV bolus injections used in this study.

Objective To evaluate the cardiovascular effects of intravenous propofol in rabbits.Study design Randomized, prospective, experimental study.Animals Thirty-one female New Zealand White rabbits.Methods Rabbits were allocated to one of two groups [propofol (P) or conscious (C)]. In C (n = 16) vascular dimensions were measured using ultrasound of the left common carotid artery (ACC) and the abdominal aorta (AA). Group P (n 15) received propofol 4.0-8.0 mg kg(-1) intravenously (IV). Anaesthesia was maintained with propofol at 1.2-1.3 mg kg(-1) minute(-1). Subsequently, three propofol injections (8 mg kg(-1)) were given. Before and for 10 minutes after each injection the following vascular and haemodynamic variables were recorded (a) at the ACC after the first injection; and (b) at the AA after the second injection: vessel diameter [D, (mm)], peak systolic, minimum diastolic, end-diastolic and average blood flow velocities [psBFV, mdBFV, edBFV, Vave (cm second(-1))], average volumetric flow [VFave (mL s(-1))], resistance index (RI) and pulsatility index (PI) mean arterial pressure (MAP), heart rate (HR), arterial oxygen saturation (SpO(2)) and end-tidal CO2 (PE'CO2). Echocardiography was performed after the third propofol bolus injection to investigate changes in cardiac parameters [fractional shortening, FS (%)].Results Intravenous propofol injections caused a significant decrease in vessel diameter, volumetric flow and edBFV, and significant increases in psBFV, RI and PI. Baseline levels for vessel diameter and psBFV were restored 6-8 minutes after injection. Propofol injection decreased FS significantly by 7 minutes after injection while MAP and HR were significantly reduced for 4 minutes.Conclusion and clinical relevance Injections of propofol (8 mg kg(-1)) produced an immediate, transient decrease in vascular diameters, a significant decrease in ventricular performance and an increase in peripheral vascular resistance (ACC and AA). Propofol should probably not be or only carefully used in rabbits with ventricular dysfunction.

Tirapazamine (TPZ) ist eine Substanz mit selektiver Zytotoxizität für hypoxische (Tumor-)Zellen und wird deswegen zusammen mit Strahlentherapie angewendet. TPZ hat darüber hinaus die Eigenschaft, die Wirkung von Cisplatin zu steigern. Bisher gibt es nur wenige detaillierte Daten zur Toxizität der Kombinationstherapie. Die Autoren untersuchten Allgemeinbefinden und histologische Organveränderungen nach Gabe von TPZ plus Cisplatin im Mausmodell.

Background and Objectives: We report first results of animal trials using an improved laser osteotomy technique. This technique allows effective bone cutting without the usual thermal tissue damage.Study Design/Materials and Methods: A comparative in vivo study on mandibles of seven canines was done with a mechanical saw and a CO2 laser based osteotome with a pulse duration of 80 microseconds. The laser incisions were performed in a multipass mode using a PC-controlled galvanic beam scanner and an assisting water spray.Results: A complete healing through a whole bony rearrangement of the osteotomy gap with newly build lamellar Haversian bone was observed 22 days after the laser operations under optimal irradiation conditions.Conclusions: An effective CO2 laser osteotomy without aggravating thermal side effects and healing delay is possible using the described irradiation technique. It allows an arbitrary cut geometry and may result in new advantageous bone surgery procedures.

Background: Performing radiobiological experiments under general anesthesia is, in many cases, superior to treatment in unanesthetized animals or with intraperitoneal (i.p.) anesthesia. This is especially true for experiments where highly fractionated treatment schedules are used. Materials and Methods: An anesthesia system was employed to overcome several of the limitations associated with the use of pentobarbital and other i.p.-administered anesthetics in experimental radiotherapy. Results: Several different experiments with a total of 152 mice were performed. The total of all anesthesia exposures amounted to approximately 1,520. The duration of anesthesia ranged from 3 to 5 min per session. No complications related to the anesthetic procedure were observed. Conclusion: The present anesthesia/irradiation setup is a simple, safe and perfectly reproducible system where even multiple fractionated treatments can be performed under anesthesia with excellent tolerance. Our system allows easy and fast handling and immobilization and thus reduces experimental times.

OBJECTIVE To compare the quality of surgical anaesthesia and cardiorespiratory effects of three intramuscular (IM) anaesthetic combinations in rabbits. STUDY DESIGN Prospective randomized cross-over experimental study. ANIMALS Nineteen adult female chinchilla mixed-bred rabbits weighing 3.9 +/- 0.8 kg. METHODS Rabbits were given one of three IM anaesthetic combinations: 0.25 mg kg(-1) medetomidine and 35.0 mg kg(-1) ketamine (M-K), 0.20 mg kg(-1) medetomidine and 0.02 mg kg(-1) fentanyl and 1.0 mg kg(-1) midazolam (M-F-Mz) and 4.0 mg kg(-1) xylazine and 50 mg kg(-1) ketamine (X-K). The effects of anaesthesia on nociceptive reflexes, circulatory and respiratory function were recorded. Statistical analyses involved repeated measures anova with paired Student's t-test applied post hoc. P-values <0.05 were considered as significant. RESULTS Reflex loss was most rapid and complete in M-K recipients, whereas animals receiving M-F-Mz showed the longest tolerance of endotracheal intubation (78.1 +/- 36.5 minutes). Loss of righting reflex was significantly most rapid (p < 0.05) in the X-K group (114.7 +/- 24.0 minutes). Surgical anaesthesia was achieved in 16 of 19 animals receiving M-K, in 14 animals receiving M-F-Mz, and in seven animals with X-K, but only for a short period (7.1 +/- 11.6 minutes). This was significantly (p < 0.001) shorter than with M-K (38.7 +/- 30.0 minutes) and M-F-Mz (31.6 +/- 26.6 minutes). Heart rates were greatest in X-K recipients; lowest HR were seen in animals receiving M-F-Mz. Mean arterial blood pressure was significantly higher (about 88 mmHg) during the first hour in the M-K group. During recovery, the greatest hypotension was encountered in the X-K group; minimum values were 53 +/- 12 mmHg. Six of 19 animals in the M-F-Mz group showed a short period of apnoea (30 seconds) immediately after endotracheal intubation. Respiratory frequency was significantly lower in this group (p < 0.001). Highest values for arterial carbon dioxide partial pressures (PaCO(2)) (6.90 +/- 0.87 kPa; 52.5 +/- 6.5 mmHg) occurred after induction of anaesthesia in group M-F-Mz animals. There was a marked decrease in PaO(2) in all three groups (the minimum value 5.28 +/- 0.65 kPa [39.7 +/- 4.9 mmHg] was observed with M-K immediately after injection). Arterial PO(2) was between 26.0 and 43.0 kPa (196 and 324 mmHg) in all groups during O(2) delivery and decreased - but not <7.98 kPa - on its withdrawal. Immediately after drug injection, pH(a) values fell in all groups, with lowest values after 30 minutes (7.23 +/- 0.03 with M-K, 7.28 +/- 0.05 with M-F-Mz, and 7.36 +/- 0.04 with X-K). The X-K animals showed significantly (p < 0.001) higher pH values than medetomidine recipients. During 1 hour of anaesthesia pH values in the medetomidine groups remained below those of the X-K group. CONCLUSIONS Surgical anaesthesia was induced in most animals receiving medetomidine-based combinations. Arterial blood pressure was maintained at baseline values for about 1 hour after M-K. Transient apnoea occurred with M-F-Mz and mandates respiratory function monitoring. Oxygen enrichment of inspired gases is necessary with all three combinations. Endotracheal intubation is essential in rabbits receiving M-F-Mz. CLINICAL RELEVANCE The quality of surgical anaesthesia was greatest with M-K. All combinations allowed recoveries of similar duration. It is theoretically possible to antagonize each component of the M-F-Mz combination.

Within the framework of liver transplantation, arterialisation of the portal vein in the case of non-recanalisable thrombosis has been reactivated. However, one of the consequences of this vascular reconstruction is the development of hepatic fibrosis. Clinical experience has shown that the development of fibrosis can be avoided by reducing portal inflow. We present, as a model for the induction of hepatic fibrosis, techniques of PVA, including transplantation. For PVA, several different techniques were used: the first with reduction of the portal inflow over a stent inserted in the right renal artery (PVA-B), the second with unrestricted flow using an aortic-portal segment (PVA-APS). The third technique was orthotopic liver transplantation with unrestricted portal arterialisation (OLTx-APS). Portal blood flow was measured with an ultrasonic flow probe. To determine the degree of hepatic fibrosis the amount of hydroxyproline was measured. Quantification of relative transcript levels of procollagen I was effected with real-time PCR using the TaqMan technology on a lightcycler instrument. The extracellular matrix was visualised with picro-sirius staining. Measurements with the ultrasonic probe showed a significant increase in flow rates, both with reduced (PVA-B) and unrestricted inflow (PVA-APS; OLTx-APS). The lowest survival rate (58%) was found in the group with unrestricted portal inflow. The reason for this was a high rate of thrombosis in the in the portal vascular tree (4 out of 12). In the OLTx-APS group four animals died within the first 3 postoperative days (69%), as a result of protracted postoperative shock. The overall survival rate was the highest (85%) in the group undergoing PVA with reduction of the portal inflow. PVA with unrestricted inflow was followed by a significant increase in extracellular collagen, which showed a clear correlation with the increase in the amount of hydroxyproline, the level of the mRNA for procollagen I and picro-sirius staining. With the operative PVA techniques presented herein, different arterial flow rates in the portal vein can be investigated. In our opinion these techniques represent an excellent animal model for studying the genesis of fibrosis and antifibrotic substances. By regulating the blood flow in the arterialised portal vein hepatic fibrosis can be reduced or even avoided. After a brief period of learning the microsurgical techniques, the surgeon can limit clamping times and achieve good results with these techniques.

The objective of this study was a comparison of the volatile anaesthetics isoflurane and sevoflurane in terms of their clinical effects in gerbils (Meriones unguiculatus) (n=12 each). Induction of anaesthesia was performed in a body chamber with an anaesthetic concentration of 4.0 Vol.% at an oxygen flow of 500 ml/min for isoflurane and 8.0 Vol.% at an oxygen flow of 1000 ml/min for sevoflurane, respectively. Anaesthesia was maintained via nose cone with an anaesthetic concentration of 2.8 to 3.2 Vol.% at an oxygen flow of 200 ml/min for isoflurane and 5.0 to 5.2 Vol.% at an oxygen flow of 400 ml/min for sevoflurane. Those anaesthetic concentrations ensured reflex status conform with surgical tolerance. In spite of its higher blood-gas coefficient induction time was slightly faster for isoflurane. Recovery time was significantly longer in the isoflurane group than it was in the sevoflurane group. Both inhalants caused respiratory depression. Respiratory rate was lower in sevoflurane animals compared to isoflurane. The animals were positioned on a heating pad immediately after induction, thus a decrease of the body temperature could be prevented. Both inhalants can be recommended for usage in gerbils. Sevoflurane showed no clinical benefit compared to isoflurane.

At present there are neither clinical nor experimental data available on the influence of technical details on the quality and reproducibility of prostate lymphoscintigraphy. Six adult fox hounds received repeated transrectal ultrasound guided intraprostatic injections of a technetium 99m labeled nanocolloid to prove the influence of different techniques of injection (one central injection in both prostate lobes vs two peripheral injections in both lobes) on tracer accumulation in sentinel lymph nodes (SLN) and other organs. The reproducibility of the favored technique was examined and in a last step it was subject to scrutiny following a reduction of the injected volume to 1% of the prostate volume. The number of scintigraphically visualized SLN varied between four and seven. They were located in the region of the internal and external iliac vessels, presacrally, paravesically, and directly paraprostatically. In five of six cases, the localization was reproducible both with the central application of an identical volume as well as with the volume reduced central injection. Tracer accumulation of SLNs and other organs varied enormously. We expect that with the combination of both injection techniques, even with the reduced injection volume, an optimized prostate lymphoscintigraphy will be the outcome.

Als Beitrag zur Ermittlung der richtigen Werte der Chromgehalte von menschlichen und tierischen Geweben und Körperflüssigkeiten wurde der Chromgehalt von Laboratoriumskaninchen-Skelettmuskel neutronenaktivierungsanalytisch bestimmt. Bisherige Angaben anderer Autoren: <7,1–121 ng/g. Die Verbesserung einer in der Literatur angegebenen 51Cr-Abtrennung durch Chromylchloriddestillation und die erforderlichen Maßnahmen zur Minimierung des Chromblindwertes werden beschrieben. Dessen Hauptanteil wird durch die Restverunreinigung der Bestrahlungsampullen-Oberfläche mit Chrom bedingt und beträgt 0,049 ng Cr (ohne Gefriertrocknung) bzw. 0.12 ng Cr (mit Gefriertrocknung). Analysen von Standardreferenzmaterialien (SRM) ergaben Chromgehaltswerte, die bei NBS-Citrus Leaves mit dem Zertifikatswert, bei IAEA animal muscle (H-4) mit dem neuesten Literaturwert von 9,2±2,5 ng/g übereinstimmen. Im Falle von NBS-Orchard Leaves erwies sich, daß dieses SRM für die Überprüfung der Methode ungeeignet ist. In Analysen von Oberschenkelmuskel-Proben von Bastardkaninchen resultierten Chromgehalte von 6,2–22,9 ng/g (bezogen auf Frischgewicht). Aus dem Vergleich dieser Daten mit dem früher gefundenen Wert von 1,2 ng/g, dem Literaturwert <7,1 ng/g und dem auf Frischgewicht berechneten H-4-Wert von 2,5 ng/g folgt, daß die Chromgehalte von Säugetier-Skelettmuskel innerhalb eines breiten Bereiches liegen dürften, auch die von Muskel einer Subspecies.

Instrumental neutron-activation analysis was used for the determination of Ca, Cr, Fe, Co, Ni, Zn, Mo, Ag, Sb, and Hg. Blood and tissue samples of 70 mg each were analysed and, from these, changes in the concentrations of calcium, iron, and zinc in affected tissue were established. In this article the results of the behaviour of calcium and iron are reported. The calcium concentration of the fracture haematoma blood (FHB) is about 20 times higher than that of arterial or venous blood (rabbits). The level and the change with time of the calcium concentration in FHB-deposits (rabbits) can be explained by the participation of calcium in the haemolysis of the erythrocytes of the FHB which has been injected for the formation of the deposits. The behaviour of the iron in the FHB-deposits is in agreement with this explanation. The change in calcium concentration in the crust of punch-hole wounds in the skin (rats) can be attributed to the mobilization of calcium for fibrin formation. As a reason for the level and the change with time of the iron concentration in the tissue in the area of fascia and muscle incision wounds (rabbits) the participation of iron in the formation of collagen is discussed. From comparison of the behavoiur of the iron in the FHB-deposits with that in the area of incision wounds it follows that iron enrichments in the area of a complication-free wound are not predominantly caused by a wound haematoma.

Die verschiedentlich aufgeworfene und zum Teil positiv beantwortete Frage nach der Entstehung eines Lungenkrebses durch inhaliertes Eisenoxyd wurde durch Versuche mit dem Peritonealtest an Mäusen überprüft.