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ABSTRACT: To evaluate the cardiorespiratory effects and plasma concentrations of medetomidine-midazolam-ketamine (MMK) combinations administered by intramuscular (IM) or subcutaneous (SC) injection in sable ferrets (Mustela putorius furo).
Prospective randomized experimental study.
Eighteen adult ferrets: weight median 1.19 (range 0.81-1.60) kg.
Animals were allocated to one of three groups: group IM07 received 20 μg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 7 mg kg(-1) ketamine IM; group IM10 20 μg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 10 mg kg(-1) ketamine IM; and group SC10 20 μg kg(-1) medetomidine, 0.5 mg kg(-1) midazolam and 10 mg kg(-1) ketamine SC. Following instrumentation, cardiorespiratory parameters and plasma drug concentrations were measured every 5 minutes (T5-T30) for 30 minutes Ferrets were then euthanased. Data were analysed using anova for repeated measures. p<0.05 was considered significant.
Results are mean ± SD. Induction of anaesthesia (minutes) in IM07 and IM10 [2 (1)] was significantly faster than in SC10 [5 (2)]. All groups demonstrated the following: results given as groups IM07, IM10 and SC10 respectively. Mean arterial blood pressures (mmHg) were initially high [186 (13); 174 (33) and 174 (9) at T5] but decreased steadily. Pulse rates were initially 202 (20), 213 (17) and 207 (33) beats minute(-1) , decreasing with time. PaO(2) (mmHg) was low [54.0 (8), 47.7 (10) and 38.5 (1)] at T5, although in groups IM07 and IM10 it increased over time. Plasma concentrations of all drugs were highest at T5 (36, 794 and 8264 nmol L(-1) for medetomidine, midazolam and ketamine, respectively) and decreased thereafter: for both midazolam and ketamine, concentrations in IM07 and IM10 were higher than SC10.
MMK combinations containing either 7 or 10 mg kg(-1) ketamine and given IM are suitable combinations for anaesthetising ferrets, although the observed degree of hypoxaemia indicates that oxygen administration is vital.
Veterinary Anaesthesia and Analgesia 09/2011; 38(5):439-50. · 0.94 Impact Factor
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Laboratory Animals 02/2011; 45(2):127-8. · 1.21 Impact Factor
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ABSTRACT: 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.
Canadian journal of veterinary research = Revue canadienne de recherche vétérinaire 10/2010; 74(4):286-98. · 0.94 Impact Factor
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ABSTRACT: To evaluate the short-term cardiovascular effects of IV administration of dipyrone (metamizole) as an intraoperative analgesic during total IV anesthesia with propofol.
6 healthy female New Zealand White rabbits.
Anesthesia was induced with propofol (4.0 to 8.0 mg/kg, IV) and maintained with the same drug (1.2 to 1.3 mg/kg/min, IV). After induction, 3 doses of dipyrone (65 mg/kg each) were administered IV at 25-minute intervals. Before and for 10 minutes after each dipyrone injection, the following vascular and hemodynamic variables were recorded at the left common carotid artery every minute after the first injection: vessel diameter; peak systolic, minimum diastolic, end-diastolic, and mean blood flow velocities; mean volumetric flow; resistance and pulsatility indices; mean arterial blood pressure (MAP); heart rate; arterial oxygen saturation (SpO(2)); and end-tidal partial pressure of CO(2) (PETCO(2)). Echocardiography was performed after the second injection. The same variables were measured at the abdominal aorta (AA) after the third injection.
Dipyrone injections caused a significant, transient decrease in the resistance index at the AA. Also detected were a minor decrease in pulsatility index at the left common carotid artery and a minor increase in end-diastolic blood flow velocity at the AA. The MAP, heart rate, SpO(2), and PETCO(2) did not significantly change after injections. A comparison of HR and MAP after the first and third bolus injections revealed only minor changes.
Dipyrone used with propofol anesthesia in rabbits appeared not to significantly impair cardiovascular and hemodynamic function.
American Journal of Veterinary Research 11/2009; 70(11):1407-15. · 1.27 Impact Factor
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ABSTRACT: To evaluate short-term cardiovascular effects after IV administration of boluses of fentanyl in rabbits.
6 healthy New Zealand White rabbits.
Each rabbit was anesthetized with propofol (4.0 to 8.0 mg/kg, IV); anesthesia was maintained by administration of propofol (1.2 to 1.3 mg/kg/min, IV). Subsequently, 3 injections of fentanyl (0.0053 mg/kg) were administered. Before and for 10 minutes after injections, the following variables were measured: vessel diameter, peak systolic blood flow velocity, minimum diastolic blood flow velocity, end-diastolic blood flow velocity, time-average blood flow velocity, mean volumetric flow (VFmean), resistance index (RI), and pulsatility index for the left common carotid artery after the first injection and abdominal aorta after the third injection; mean arterial pressure (MAP); heart rate (HR); arterial oxygen saturation; end-tidal partial pressure of carbon dioxide; and body temperature. Echocardiography was performed after the second injection.
Fentanyl injections caused a transient and significant decrease in diameter and VFmean of the abdominal aorta and end-diastolic blood flow velocity of the left common carotid artery and an increase in peak systolic blood flow velocity and RI of the left common carotid artery. Also, MAP, HR, and body temperature decreased significantly after injections.
Fentanyl injections induced a short-term decrease of vessel diameter in the abdominal aorta and increased resistance in the distal distribution area of the left common carotid artery. Results revealed decreases in MAP, HR, and body temperature, with an increasing effect after the third bolus injection, which indicated a cumulative drug effect.
American Journal of Veterinary Research 04/2009; 70(3):409-17. · 1.27 Impact Factor
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ABSTRACT: To evaluate the cardiovascular effects of intravenous propofol in rabbits.
Randomized, prospective, experimental study.
Thirty-one female New Zealand White rabbits.
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 CO(2) (Pe'CO(2)). Echocardiography was performed after the third propofol bolus injection to investigate changes in cardiac parameters [fractional shortening, FS (%)].
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.
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.
Veterinary Anaesthesia and Analgesia 04/2008; 35(2):100-12. · 0.94 Impact Factor
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ABSTRACT: Tirapazamine (TPZ) reportedly enhances the tumor cell killing effect of cisplatin up to fivefold and it is an attractive drug for combination with radiotherapy. We evaluated the toxicity of a fractionated combined treatment.
Murine RIF-1 fibrosarcomas growing on the right hind foot of C3-H mice were used. Within 2 weeks, animals were treated with six i.p. injections of TPZ (43.2-172.8 mg/kg total), and/or cisplatin (24 mg/kg total) and ten fractions of 2 Gy to the tumor. All treatments were carried out under anesthesia. Maximum follow-up was 35 days. The local tumor control was determined by calculating the tumor doubling time t (2vo). In addition to standard toxicity assessment, the major inner organs were examined histologically.
The administration of low TPZ doses to the cisplatin/radiotherapy treatment caused only little changes in tumor doubling time (t (2vo)) and led to a lethality rate of 15-30%. Higher TPZ doses caused an increase in t (2vo), but also a further increase in lethality and toxicity in particular to the heart, liver, kidney and stomach. Cisplatin/radiotherapy treatment without TPZ produced no severe toxicity.
This is a detailed study of both the acute and delayed toxicities of combined TPZ treatment in a mouse model. In our study the addition of TPZ to the cisplatin/radiotherapy treatment caused a significant increase in toxicity with only moderate effect on the tumor.
Journal of Cancer Research and Clinical Oncology 03/2008; 134(2):137-46. · 2.56 Impact Factor
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Ajit S Mallik,
Max A Fichter,
Susanne Rieder,
Grozdana Bilic,
Sofia Stergioula, Julia Henke,
Karl-Theo M Schneider,
Juozas Kurmanavicius,
Edgar Biemer,
Roland Zimmermann,
Andreas H Zisch,
Nikolaos A Papadopulos
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ABSTRACT: To explore a surgical plug formed from decellularized term human amnion membrane for fetoscopic closure of iatrogenic defects in fetal membranes in a rabbit model.
The study was performed in eight rabbit does. Punctures were created at midgestational day 23 by 14-gauge needle fetoscopy on surgically exposed rabbit amniotic sacs. The entry sites were fetoscopically plugged either with decellularized term human amnion membrane (n=10) or previously successful commercial collagen matrix foil (n=10), followed by their primary fixation with fibrin glue and myometrial suturing. Seven punctured sacs without any plugging and 31 sacs without any manipulation served as two reference groups. Amniotic integrity and fetal parameters were assessed at gestational day 30.
We established a facile method to prepare sheets of decellularized term human amnion membrane and verified its nontoxicity and cell compatibility in vitro. Decellularized term human amnion membrane sheets could be delivered precisely and controlled by fetoscopy as compact plugs into amniotic defects. The surgical handling characteristics of decellularized term human amnion membrane were better than the commercial collagen matrix foil. Treatment with human decellularized term human amnion membrane was comparable to treatment with the collagen matrix with regard to efficiency in restoring amniotic integrity. Seventy-five percent and 71.4% of amniotic sacs treated with decellularized term human amnion membrane or the commercial collagen matrix foil, respectively, showed amniotic integrity, compared with 25% in the left-open study group. Histology at the 1 week experimental endpoint showed no evidence for inflammation or beginning of anatomic healing of grafted, decellularized term human amnion membrane.
Fetoscopic delivery of plugs made of decellularized term human amnion membrane presents a potentially practical surgical method to restore amniotic integrity of punctured fetal membranes.
III.
Obstetrics and Gynecology 12/2007; 110(5):1121-9. · 4.73 Impact Factor
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Bettina Wagner,
Martina Anton,
Stephan G Nekolla,
Sybille Reder, Julia Henke,
Stefan Seidl,
Renate Hegenloh,
Masao Miyagawa,
Roland Haubner,
Markus Schwaiger,
Frank M Bengel
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ABSTRACT: We sought to investigate the usefulness of integrated positron emission tomography (PET) and computed tomography (CT) for in vivo characterization of an angiogenesis-directed molecular intervention.
Controversies about the effectiveness of molecular therapies for cardiovascular disease have prompted the need for more powerful noninvasive imaging techniques.
In a model of regional adenoviral transfer of the VEGF(121) gene to myocardium of healthy pigs, PET-CT using multiple molecular-directed radiotracers was employed.
Two days after gene transfer, successful transgene expression was noninvasively confirmed by a reporter probe targeting co-expressed HSV1-sr39tk reporter gene. The CT-derived ventricular function and morphology remained unaltered (left ventricular ejection fraction 57 +/- 5% in adenovirus-injected animals vs. 53 +/- 5% in controls; p = 0.36). Increased regional perfusion was identified in areas overexpressing VEGF (myocardial blood flow during adenosine-induced vasodilation 1.47 +/- 0.49 vs. 1.14 +/- 0.27 ml/g/min in remote areas; p = 0.01), corroborating in vivo effects on microvascular tone and permeability. Finally, regional angiogenesis-associated alpha(v)beta3 integrin expression was not enhanced, suggesting little contribution to the perfusion increase. Fusion of CT morphology and tracer-derived molecular signals allowed for accurate regional localization of biologic signals. Findings were validated by control vectors, sham-operated animals, and ex vivo tissue analysis.
Integrated PET-CT has the potential to dissect cardiovascular biologic mechanisms from gene expression to physiologic function and morphology. The VEGF overexpression in healthy myocardium increases myocardial perfusion without significant up-regulation of alpha(v)beta3 integrin adhesion molecules early after the intervention.
Journal of the American College of Cardiology 12/2006; 48(10):2107-15. · 14.16 Impact Factor
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ABSTRACT: To evaluate maxillary growth following in utero repair of surgically created cleft lip and alveolar (CLA)-like defects by means of three-dimensional (3D) computer tomographic (CT) cephalometric analysis in the mid-gestational sheep model.
In 12 sheep fetuses a unilateral CLA-like defect was created in utero (untreated control group: 4 fetuses). Four different bone grafts were used for the alveolar defect closure. After euthanasia, CT scans of the skulls of the fetuses, 3D reconstructions, and a 3D-CT cephalometric analysis were performed.
The comparisons between the operated and nonoperated skull sides as well as of the maxillary asymmetry among the experimental groups revealed no statistically significant differences of the 12 variables used.
None of the surgical approaches used for the in utero correction of CLA-like defects seem to affect significantly postsurgical maxillary growth; however, when bone graft healing takes place, a tendency for almost normal maxillary growth can be observed.
Fetal Diagnosis and Therapy 02/2006; 21(1):105-14. · 1.05 Impact Factor
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ABSTRACT: In this study we aimed to set up an in vitro culture of the rabbit amnion in order to support in vivo fetal membrane healing capacity following fetoscopy. Fetal membranes were collected from a mid-gestational rabbit, and cultured on collagen support material for 14 days. 34 rabbits at 22-23 days gestational age (GA) underwent fetoscopy. The entry site was randomly allocated to 4 closure technique study groups: group I, human amnion membrane (n = 23); group II, collagen foil (n = 16); group III, collagen plug (n = 19), and group IV, collagen plug with cultured amnion cells (n = 19). In all groups membrane access sites were additionally sealed with fibrin sealant, and the myometrium was closed with sutures. Fetal survival, amnion membrane integrity, and the presence of amniotic fluid were evaluated at 30 days GA. Cultures showed good survival in the collagen support material. Increased cellularity, survival and proliferations were observed. The amnion at the access site resealed in 58-64% of cases in groups II-IV, but none of the tested techniques was significantly better than the other. Histological examination indirectly revealed the anatomic repair of the membranes, since no entrapment of the membranes could be demonstrated in the myometrial wound.
Fetal Diagnosis and Therapy 02/2006; 21(6):494-500. · 1.05 Impact Factor
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ABSTRACT: To develop a 3D CT cephalometric analysis for maxillary growth evaluation of sheep fetuses operated in utero, and to evaluate the reliability of this analysis by comparing it with a direct cephalometric analysis on dry skulls.
Five skulls of operated sheep fetuses were used, which after preparation were CT scanned and a 3D reconstruction was performed. A cephalometric analysis was performed directly on the dry skulls as well as on the reconstructed 3D CT images. In total, 56 linear distances were measured. In order to access the error of the method, the procedure was repeated after a 2 week interval.
The comparison between the direct cephalometric and the 3D CT analysis revealed that only 5 variables were significantly different. The evaluation of the error of method revealed that 7 variables of the direct cephalometric analysis and none of the 3D CT analysis differed significantly.
According to the results of this study, it can be concluded that a cephalometric analysis on 3D CT reconstructed images of the skulls includes fewer identification errors and seems to be an accurate and reliable method that could be regarded at least as equivalent to conventional cephalometry.
Journal of Cranio-Maxillofacial Surgery 09/2005; 33(4):229-37. · 1.64 Impact Factor
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ABSTRACT: To compare the quality of surgical anaesthesia and cardiorespiratory effects of three intramuscular (IM) anaesthetic combinations in rabbits.
Prospective randomized cross-over experimental study.
Nineteen adult female chinchilla mixed-bred rabbits weighing 3.9 +/- 0.8 kg.
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.
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.
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.
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.
Veterinary Anaesthesia and Analgesia 09/2005; 32(5):261-70. · 0.94 Impact Factor
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ABSTRACT: 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.
Transplant International 06/2005; 17(12):822-33. · 2.92 Impact Factor
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Martina Anton,
Constanze Wittermann,
Roland Haubner,
Marcus Simoes,
Sybille Reder,
Bryan Essien,
Bettina Wagner, Julia Henke,
Wolf Erhardt,
Steffi Noll,
Neil R Hackett,
Ronald G Crystal,
Markus Schwaiger,
Bernd Gansbacher,
Frank M Bengel
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ABSTRACT: Coexpression of a reporter gene and a therapeutic gene may allow for noninvasive monitoring of cardiac gene therapy. We sought to evaluate the usefulness of an adenoviral vector expressing mutant herpesviral thymidine kinase reporter gene (HSV1-sr39tk) and vascular endothelial growth factor (VEGF) 121 in independent expression cassettes (Ad4tk).
Accumulation of 14C-2'-fluoro-5-methyl-1-beta-D-arabinofuranosyluracil (FIAU) and 9-(4-18F-fluoro-3-hydroxymethylbutyl)guanine (FHBG) as reporter probes, and secretion of VEGF into medium, were determined for Ad4tk-infected H9c2 rat cardiac cells in vitro.
In vitro tracer uptake increased with increasing vector concentration and over time. It was comparable to cells infected with adenovirus expressing only wild-type HSV1-tk (reporter probe: 14C-FIAU) or mutant HSV1-sr39tk (reporter probe: 18F-FHBG). No significant uptake was observed in cells infected with adenovirus expressing VEGF alone. With increasing vector concentration, Ad4tk-infected cells increasingly released VEGF into medium. VEGF production correlated significantly with cellular reporter probe uptake (r = 0.93; P = 0.0003).
The usefulness of a vector coexpressing HSV1-tk and VEGF for noninvasive imaging of expression of a therapeutic transgene has been demonstrated in vitro. This approach may allow for future in vivo monitoring of cardiac angiogenesis gene therapy.
Journal of Nuclear Medicine 11/2004; 45(10):1743-6. · 6.38 Impact Factor
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Volker Müller,
Daniela Brummer,
Hermann Kissler,
Süleyman Yedibela,
Michael Bauer,
Wolf Erhardt, Julia Henke,
Kerstin Amann,
Andrea Tannapfel,
Werner Hohenberger,
Rudolf Ott
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ABSTRACT: Portal vein arterialization (PVA) has been proposed as a technical variant in liver transplantation in the case of non-recanalizable thrombosis. The present study investigates the effects of the arterialized portal vein on the function, morphology, and regenerative behavior of the liver.
Different PVA techniques, including orthotopic liver transplantation, were used in a rat model. Portal blood flow was measured using a ultrasonic flowmeter. The regeneration capacity was determined on the basis of the increase of liver weight and the proliferating cell nuclear antigen index. The amount of hydroxyproline and the transcript levels of procollagen I were measured to determine the degree of fibrosis. The extracellular matrix was visualized with Picro-Sirius staining.
The measurements obtained with an ultrasonic probe revealed a significant increase in portal blood flow after PVA. The regeneration capacity in the groups after PVA with no flow reduction was comparable to that of the control. Liver transplantation and PVA with no flow reduction was followed by a significant increase (four- to sixfold) in the amount of hydroxyproline and the level of the mRNA for procollagen I. In the Picro-Sirius staining, periportal and perivascular fibrosis with incipient formation of septa was seen. After reduction of the portal blood flow, these effects were significantly less pronounced.
These operative techniques represent an excellent small animal model for studying the mechanism of liver regeneration and the genesis of fibrosis in liver and vessel tissue. The presenting findings indicate that the negative effects of "overarterialization" may be largely avoided by reducing portal blood flow. This implies that permanent PVA in clinical liver transplantation should be performed only in conjunction with a down-regulation of portal flow.
Transplantation 11/2004; 78(8):1159-65. · 4.00 Impact Factor
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ABSTRACT: The volatile anesthetic isoflurane was tested for its effect on cochlear function by means of measuring distortion product otoacoustic emissions (DPOAE) and spontaneous otoacoustic emissions (SOAE) in the mustached bat (Pteronotus parnellii parnellii). Averaged growth functions of DPOAE and spontaneous otoacoustic emissions were assessed and compared between the control group (no isoflurane application) and the isoflurane group (application of isoflurane at vaporizer settings sof about 1.5-2%). Isoflurane significantly increases the DPOAE amplitude, e.g. at a primary tone level l2 of 40 dB SPL by 10.7 dB. Additionally, the incidence of SOAEs was highly increased during application of isoflurane. The sound-evoked efferent effect on the generation of otoacoustic emissions was significantly reduced in the isoflurane group. We suggest that isoflurane might affect the postsynaptic action of acetylcholine (ACh) released by the efferent terminals of outer hair cells (OHCs). This could lead to the observed decrease of efferent suppression and to a disinhibition of cochlear amplification.
Hearing Research 09/2004; 194(1-2):135-42. · 2.70 Impact Factor
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ABSTRACT: The success of intrauterine surgery in treating non-life-threatening malformations such as myelomeningocoele, has also renewed strong interest in using this technique for treating craniofacial malformations. Nevertheless, the only experimental cleft-like defect models known, are those concerning wound healing of soft tissues.
Attempts were made to repair artificial cleft-like defects including transplantation of 11 autogenous foetal bone grafts from the iliac crest or ulna, and were randomly assigned to three study groups, using the mid-gestational sheep model. In a 4th study group, lyophilized collagen, a bone-regenerating bioresorbable implant material, was used to fill the alveolar defect.
In all groups, there was a slight degree of asymmetry and thinning of the lip. Radiological studies demonstrated a variable degree of abnormality of the maxilla, ranging from none to a mild deviation. Three-dimensional computer tomography, two-dimensional maximal intensity projection findings, and histological analysis confirmed bony healing of the alveolar cleft-like defect.
Intrauterine autogenous foetal bone transplantation for the repair of cleft-like defects in the sheep is feasible. This is a reliable and valuable model toward a possible clinical application for intrauterine treatment of clefts.
Journal of Cranio-Maxillofacial Surgery 09/2004; 32(4):199-210. · 1.64 Impact Factor
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Frank M Bengel,
Martina Anton,
Thomas Richter,
Marcus V Simoes,
Roland Haubner, Julia Henke,
Wolf Erhardt,
Sybille Reder,
Terry Lehner,
Wolfgang Brandau,
Peter Boekstegers,
Stephan G Nekolla,
Bernd Gansbacher,
Markus Schwaiger
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ABSTRACT: Radionuclide imaging of reporter gene expression may be useful for noninvasive monitoring of clinical cardiac gene therapy. Experience until now, however, has been limited to small animals.
To evaluate feasibility in a clinically applicable setting, pigs were studied by conventional positron emission tomography (PET) 2 days after regional intramyocardial injection of control adenovirus or adenovirus carrying herpesviral thymidine kinase reporter gene (HSV1-tk). Myocardial blood flow was quantified by use of [13N]ammonia. Subsequently, kinetics of the reporter substrate [124I]-2'-fluoro-2'-deoxy-5-iodo-1-beta-d-arabino-furanosyluracil (FIAU) were assessed over a period of 2 hours. Areas infected with adenovirus expressing HSV1-tk showed significantly elevated FIAU retention during the first 30 minutes after injection. At later times, washout was observed, and retention was not different from that in areas infected with control virus or remote myocardium. Early in vivo FIAU uptake correlated with ex vivo images, autoradiography, and immunohistochemistry for reporter gene product after euthanasia. After intramyocardial injection of both adenoviruses, myocardial blood flow was mildly elevated compared with that in remote areas, consistent with histological signs of regional inflammation.
In vivo quantification of regional myocardial transgene expression is feasible with clinical PET methodology, the radioiodinated reporter probe FIAU, and the HSV1-tk reporter gene. Radioactivity efflux after specific initial uptake was not observed previously in tumor studies, suggesting that tissue-specific differences in nucleoside metabolism influence reporter probe kinetics. By coregistering reporter gene expression with additional biological parameters such as myocardial blood flow, PET allows for noninvasive characterization of the success of cardiac gene transfer along with its functional correlates.
Circulation 11/2003; 108(17):2127-33. · 14.74 Impact Factor
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ABSTRACT: 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.
Urological Research 08/2003; 31(3):152-8. · 1.23 Impact Factor
