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Biomedical subjects

D Mettler

Publications and source records attributed to D Mettler.

At least 19 recordsLinked to original sources
PubMed2001

Systemic and topical drug administration in the pig ureter: effect of phosphodiesterase inhibitors alpha1, beta and beta2-adrenergic receptor agonists and antagonists on the frequency and amplitude of ureteral contractions.

PURPOSE: We searched for compounds that are pharmacologically active on ureteral motility for treating ureteral colic to ease retrograde access into the ureter and improve the clearance of stones or stone particles from the ureter. The effects of the alpha1-adrenergic receptor agonist phenylephrine, the nonselective beta and beta2-adrenergic receptor agonists isoproterenol and fenoterol, and the phosphodiesterase inhibitors papaverine (nonspecific) and rolipram (type IV) on the frequency and amplitude of ureteral contractions when administered intravenously or topically were investigated in pigs. MATERIALS AND METHODS: A total of 52 pigs were anesthetized. A double lumen 6Fr catheter was inserted through each renal pelvis and into the ureter, allowing perfusion of saline or drug solution into the renal pelvis and the recording of contractions from the mid portion of the ureter. RESULTS: The alpha1 and beta-adrenergic receptors of the ureter are not tonically activated by endogenous epinephrine or norepinephrine. Phenylephrine administered intravenously at a dose of 0.01 to 3 mg./kg. and topically at 0.1 to 3 mg./ml. per minute increased contraction frequency 10 and 4-fold, respectively, and contraction amplitude 2-fold each in a dose dependent manner. Arterial blood pressure increased markedly during intravenous administration of phenylephrine but was minimally affected during topical application. The phenylephrine effects were reversed by the antagonist prazosin. Isoproterenol administered intravenously at a dose of 0.01 to 10 mg./kg. and topically at 0.1 to 200 microg./ml. per minute decreased contraction frequency to 13% and 31% of controls, respectively. Contraction amplitude was not affected by intravenous administration but decreased to 59% of controls when applied topically. These effects were also observed with a slight delay in the saline perfused contralateral ureter. The heart rate also increased, suggesting absorption of the drug by the urothelium. The isoproterenol effects were blocked by the antagonist propranolol. Fenoterol administered intravenously at a dose of 0.1 to 30 microg./kg. and topically at 0.003 to 1 mg./ml. per minute decreased contraction frequency to 14% and 10% of controls, and contraction amplitude to 84% and 65%, respectively. These effects on the drug perfused ureter were also observed on the contralateral saline perfused ureter but to a lesser extent. The fenoterol effects were blocked by the antagonist propranolol. Papaverine administered intravenously at a dose of 0.001 to 3 mg./kg. decreased contraction frequency to 33% of controls. Topically administered papaverine as well as intravenous and topically administered rolipram had no relevant effect on ureteral motility. CONCLUSIONS: Intravenous phenylephrine increases, and isoproterenol and fenoterol decrease the frequency and amplitude of ureteral contractions in the pig. The same effects are observed with the topical administration of phenylephrine, which causes a significant local but not systemic side effect. Topical administration of isoproterenol and fenoterol produced local as well as systemic effects, suggesting absorption by the urothelium. However, to our knowledge a drug that relaxes ureteral peristalsis in pigs without causing systemic side effects has not yet been identified.

Administration, Topical↗
PubMed2001

Ischaemia/reperfusion contributes to colonic injury following experimental aortic surgery.

OBJECTIVES: ischaemia of the colon is an important complication of abdominal aortic aneurysm (AAA) repair. The aim of this animal study was to investigate the effect of sequential ischaemia and reperfusion on sigmoid mucosal pO2 and its association with local ET-1 release. MATERIAL AND METHODS: twelve pigs underwent colonic ischaemia followed by complete reperfusion. Six other animals were sham controls. A Clark-type microcatheter was used for continuous mucosal pO2 measurements. Serial systemic and inferior mesenteric vein blood samples were obtained for determination of ET-1 concentration. Neutrophil extravasation was assessed by tissue myeloperoxidase (MPO) activity. RESULTS: arterial occlusion was associated with a gradual decrease of mucosal pO2 and local release of ET-1. After restoration of blood flow, mucosal pO2 returned to near baseline values, whereas ET-1 reached its maximum concentration during the reperfusion period. MPO activity was significantly increased. CONCLUSIONS: colonic ischaemia and reperfusion causes neutrophil extravasation and local ET-1.

Animals↗
PubMed2000

Hepatic artery embolisation with a novel radiopaque polymer causes extended liver necrosis in pigs due to occlusion of the concomitant portal vein.

BACKGROUND/AIM: In an attempt to overcome some of the problems encountered with the materials available for liver embolisation, we investigated a novel radiopaque polymer of the polyurethane family (Degra-Bloc). METHODS: Hepatic artery embolisation of one liver lobe using polyurethane was performed in 19 healthy pigs. Microcirculatory changes were assessed by laser Doppler flowmetry. Radiological and pathological examinations of the livers, hearts and lungs removed provided information about the extent and effect of the embolisation. RESULTS: None of the pigs died due to hepatic failure or toxicity of polyurethane. Microcirculation of embolised liver lobes significantly decreased from 106 (+/-15) perfusion units (PU) to 45 (+/-6) PU immediately after embolisation and further to 28 (+/-7) PU before euthanasia. At this time conventional and angiographic X-ray controls demonstrated the radiopaque casts extending up to the peripheral arteries with signs of degradation over time but without formation of collateral vessels. The main pathological findings consisted of destruction of the portal tract structures and also of large areas of liver necrosis. Polyurethane was encountered in arterioles as small as 10-20 microm, but not in liver sinusoids, hearts or lungs. CONCLUSIONS: The novel polymer called DegraBloc is a biocompatible, slowly degradable, radiopaque embolic agent. The occlusion of the arterial tree up to the smallest arteriolar diameter combined with concomitant portal vein occlusion leads to sharp segmental necrosis in pig livers without formation of significant collaterals and without systemic embolism. In the treatment of liver tumours polyurethane might provide a promising alternative to conventional embolic materials, provided that it is used with care in patients with advanced liver cirrhosis.

Animals↗
PubMed1999

Experimental study of neorectal physiology after formation of a transverse coloplasty pouch.

BACKGROUND: A novel transverse coloplasty pouch (TCP) with a larger neorectal volume than a straight coloanal anastomosis (CAA) but a smaller volume than a short colonic J pouch (CJP) may improve short-term function after rectal excision. METHODS: Twelve pigs were investigated 6 weeks after complete rectal excision followed by reconstruction with a CAA, CJP or TCP. The results were compared with findings in the normal pig rectum. RESULTS: The colonic transit times assessed by radio-opaque marker transit were 24 h for CAA, 60 h for CJP and 32 h for TCP. Non-operated control pigs had a mean transit time of 46 h. Pigs that had a CJP developed colonic dilatation and substantial faecal impaction. Colonic electrostimulation induced an adaptive relaxation in the normal rectum but a pressure increase in all neorecta, particularly after CAA. The neorectal longitudinal smooth muscle layer in pigs with a TCP was significantly thicker than that in pigs with a CAA or CJP; its thickness was closest to that of the normal pig rectum. Colonic smooth muscle layers 10 cm proximal to the coloanal anastomosis, above the neorecta, were significantly thicker after CJP than after CAA or TCP formation. No significant difference in microcirculation was observed between the three restorative procedures. CONCLUSION: Accelerated colonic transit and a lack of adequate relaxation upon endoluminal pressure increase was associated with urgency and incontinence after CAA. Delayed colonic transit, faecal impaction and ineffective muscular hypertrophy due to pouch dilatation and constipation indicated evacuation problems after CJP construction. Functional and morphometric data for TCPs suggested almost normal defaecation. Of the three restorative procedures, the data for TCPs were most similar to those obtained in the normal pig rectum at short-term follow-up.

Animals↗
PubMed1999

A novel colon pouch and its comparison with a straight coloanal and colon J-pouch--anal anastomosis: preliminary results in pigs.

BACKGROUND: Early functional results after complete rectal resection and straight coloanal anastomosis are often characterized by frequent bowel movements, urgency, and varying degrees of stool incontinence. The formation of a colon reservoir improves early and long-term function. We evaluated the feasibility of a novel, modified design of a colon pouch--anal anastomosis in pigs and compared the results with those of pigs with straight coloanal anastomosis and colon J-pouch. METHODS: Complete rectal resection followed by either a straight coloanal anastomosis, a colon J-pouch, or a novel design of a colon pouch was performed in equal numbers in 15 pigs. By transversely closing a longitudinal colotomy, the new, technically simpler pouch is formed. Functional results were assessed during a period of 6 weeks. RESULTS: All 15 procedures were successful. The novel colon pouch required less surgical time than the colon J-pouch, and the formation of the pouches did not reduce tissue perfusion as assessed by laser Doppler flowmetry. The mean volume of the novel colon pouch was significantly smaller than the volume of the colon J-pouch. All the pigs with the novel colon pouch had normal stool frequency and consistency during a period of 6 weeks. In the group with straight coloanal anastomosis, two pigs had increased frequency of defecation, one pig showed signs of urgency and perianal dermatitis, and three had substantially reduced stool consistency. Of the four pigs with colon J-pouch, three had signs of impaired pouch evacuation and two had reduced stool frequency. CONCLUSIONS: The novel colon pouch is feasible in pigs and technically simpler than the colon J-pouch. These preliminary results indicate that the smaller capacity of this pouch seems sufficient for normal defecation. Its short-term functional results were better than those after reconstruction with a colon J-pouch or a straight coloanal anastomosis.

Anal Canal↗
PubMed1998

Experimental transplantation of size-reduced, adult kidneys into pediatric recipients.

BACKGROUND: Renal transplantation in infants is frequently complicated by graft thrombosis and accelerated rejection reactions. We herein tested the hypothesis that the amount of blood required to sustain normal perfusion of an adult renal allograft transplanted into a pediatric recipient would surpass the cardiac output and aortic blood flow of the recipient and that the ensuing low flow in full-size grafts (FSG) would induce a release of thrombogenic substances. METHODS: In a porcine renal transplant model, adult FSG were transplanted into pediatric recipients. Macro- and microhemodynamic as well as metabolic data were recorded. Surgically size-reduced grafts (RSG) served as controls. RESULTS: Donor weight was 55.1+/-4.8 kg and 9.6+/-0.9 kg for recipients. FSG weight was 122+/-16 g and 65+/-14 g for RSG. Blood flow in donor kidneys was 20% higher than the infrarenal aortic blood flow of recipients. After reperfusion, mean arterial pressure in recipients of FSG but not RSG dropped to 64 mmHg, despite an increase in cardiac output by 60%. FSG but not RSG were polyuric and proteinuric. The release of endothelin and thromboxane B2 into the circulation was higher from FSG when compared with RSG (P<0.05 for endothelin after 60 min; NS for thromboxane B2). CONCLUSIONS: After transplantation of FSG into pediatric recipients, the macrohemodynamic limitations of the recipient cause microcirculatory disturbances in the graft, which contribute to the release of vasoconstrictive and prothrombotic substances and an impaired early graft function. Some of those effects can be ameliorated by surgically size reducing the renal graft.

Animals↗
PubMed1998

Endobronchial photodynamic therapy: comparison of mTHPC and polyethylene glycol-derived mTHPC on human tumor xenografts and tumor-free bronchi of minipigs.

BACKGROUND AND OBJECTIVE: Photodynamic therapy (PDT) with mTHPC and polyethylene glycol-derived mTHPC (pegylated mTHPC) was compared on nude mice bearing human squamous cell carcinoma and adenocarcinoma xenografts. The same treatment regimens were applied to the bronchi of tumor-free minipigs to assess injury to normal tissue. STUDY DESIGN/MATERIALS AND METHODS: Laser light (652 nm, 20 J/cm2) was delivered as surface radiation to the xenografts 4 days after intraperitoneal administration of 0.1 mg/kg mTHPC or an equimolar dose of pegylated mTHPC, respectively. The extent of tumor necrosis was assessed by histomorphometry. Endobronchial PDT was performed on the bronchi of minipigs with the same drug and light doses at drug-light intervals ranging from 12-96 hr. RESULTS: Both sensitizers produced larger necrosis of squamous cell carcinoma and adenocarcinoma xenografts than was observed in untreated controls (P < 0.005). Pegylated mTHPC led to larger tumor necrosis than mTHPC in squamous cell carcinoma (P < 0.001), but not in adenocarcinoma xenografts. mTHPC-PDT resulted in ulceration and necrosis of bronchial mucosa in minipigs at drug-light intervals ranging from 12-48 hr, which was not observed after use of pegylated mTHPC. CONCLUSIONS: In this setting, pegylated mTHPC had advantages as a photosensitiser compared to mTHPC.

Adenocarcinoma↗
PubMed1998

Isolated lung perfusion: single-pass system versus recirculating blood perfusion in pigs.

BACKGROUND: Cytostatic isolated lung perfusion has been advocated for treating pulmonary metastasis of soft tissue sarcoma. Different techniques of isolated lung perfusion have been developed. METHODS: Isolated lung perfusion with and without doxorubicin was performed on white pigs during 15 minutes either by a single-pass system (n = 7) or by a recirculating-blood perfusion system (n = 7). Three animals with endovenous drug application served as controls. Leakage was assessed using isotopic tracers. Perfusion-induced lung tissue injury was determined by postperfusion chest radiographs, by angiotensin-converting enzyme-to-protein ratio in the plasma and in the bronchioalveolar lavage fluid, and by wet-to-dry weight ratio and histologic examination of lung biopsy specimens at 20 and 50 minutes. Doxorubicin concentration in lung tissue and plasma was compared between the three study groups. RESULTS: All isolated lung perfusion studies were successfully performed without significant systemic leakage (< 0.6%). Wet-to-dry weight ratio was significantly lower after single-pass as compared with recirculating-blood perfusion and endovenous drug application at both time points (5.0 +/- 1.1 and 5.3 +/- 0.8 for single-pass versus 6.6 +/- 1.1 and 6.9 +/- 0.5 for recirculating-blood versus 6.6 +/- 0.2 and 5.9 +/- 0.7 for the control group, respectively; p < 0.05). Angiotensin-converting enzyme-to-protein plasma ratio in the single-pass group was significantly lower only at 20 minutes (6.3 +/- 2.4 versus 9.3 +/- 1.0 versus 9.7 +/- 1.9, respectively; p < 0.05) but not at 50 minutes. Angiotensin-converting enzyme-to-protein ratio in bronchoalveolar lavage fluid, histology of lung biopsy specimens, and chest radiographs did not differ significantly between the three groups. Doxorubicin lung tissue concentration was not significantly different after single-pass (17.5 micrograms/g) and recirculating-blood perfusion (21.9 micrograms/g), but was significantly higher than after endovenous drug application (3.0 micrograms/g; p < 0.01). CONCLUSIONS: Both isolated lung perfusion techniques resulted in a sixfold to sevenfold higher doxorubicin lung tissue concentration than after endovenous application. Isolated lung perfusion-induced lung injury was similar for both techniques, but recirculating-blood perfusion appeared to result in more acute lung injury and was technically more demanding than single-pass perfusion.

Animals↗
PubMed1998

Cytostatic lung perfusion by use of an endovascular blood flow occlusion technique.

BACKGROUND: Different modalities of cytostatic lung perfusion were compared regarding plasma and tissue drug concentrations to assess the efficacy of an endovascular blood flow occlusion technique. METHODS: A cytostatic lung perfusion study with doxorubicin hydrochloride was performed on large white pigs (n = 12). Plasma and tissue concentrations of doxorubicin were compared for isolated lung perfusion with open cannulation (ILP), blood flow occlusion perfusion with open cannulation of the pulmonary artery alone (BFO), and intravenous drug administration (i.v.). In a fourth group, thoracotomy-free BFO perfusion was performed by endovascular balloon catheterization of the pulmonary artery (endovascular BFO). The 3 animals in this group were used to compare the doxorubicin-perfused pulmonary tissue with the contralateral nonperfused lobes after 1 month. RESULTS: The mean lung tissue doxorubicin concentration at the end of perfusion was 19.8 +/- 1.6 microg/g after ILP, 27.6 +/- 2.2 microg/g after BFO (p = not significant), and 3.0 +/- 0.8 microg/g after i.v. perfusion (p < 0.01). Whereas doxorubicin was not detectable in the plasma in the ILP group, concentrations ranged from not detectable to 0.44 microg/mL in the BFO group and from 0.31 to 0.84 microg/mL in the i.v. group (p < 0.05). Mean myocardial tissue concentration was not significantly different after BFO than i.v. perfusion (1.1 +/- 0.5 microg/g and 1.8 +/- 0.1 microg/g, respectively). In the endovascular BFO group, balloon-blocked pulmonary artery perfusion was successfully performed in all animals, and after 1 month, lung tissue showed no cytostatic-induced histologic changes. CONCLUSIONS: Compared with ILP, BFO cytostatic lung perfusion produced an insignificantly higher lung-tissue concentration, corresponding to a sixfold to ninefold higher level than after i.v. perfusion. Plasma drug levels during BFO perfusion were lower than during i.v. perfusion. Endovascular BFO may be a promising technique for repeated cytostatic lung perfusion.

Animals↗
PubMed1998

Pulmonary function after one-lung ventilation in newborns: the basis for neonatal thoracoscopy.

BACKGROUND: To maintain good exposure during major video-assisted thoracic surgery it is necessary to deflate completely the ipsilateral lung. However, little is known about the effects of one-lung ventilation (OLV) on pulmonary function in newborn patients. METHODS: Ten neonatal domestic pigs with a mean age of 6+/-0.6 days were intubated and ventilated in pressure-controlled mode (inspired oxygen fraction=1.0). One-lung ventilation was maintained for 120 minutes. Serial measurements of hemodynamics and gas exchange were done before, during, and until 90 minutes after OLV. Pulmonary function testing was performed before and after OLV for each lung separately. RESULTS: With the inspired oxygen fraction set at 1.0, arterial oxygen saturation remained stable at 100% during OLV. Venous admixture and alveolar-arterial oxygen tension gradient increased slightly from the baseline value of 2.6% +/-0.3% to 3.8%+/-0.3% during OLV (mean+/-standard error of the mean; p=0.02), and from 358+/-28 to 407+/-18 mm Hg (not significant), respectively. Both values returned to baseline during the subsequent ventilation of both lungs. Static compliance and resistance of the ventilated lung did not change. Compliance of the collapsed lung decreased after reexpansion from 0.42+/-0.07 to 0.29+/-0.06 mL x cm H2O(-1) x kg(-1), p=0.008). Resistance remained unchanged (0.22+/-0.02 versus 0.25+/-0.05 cm H2O x L(-1) x s(-1); not significant). CONCLUSIONS: There were only minor effects on pulmonary function during and after OLV in the neonatal piglet. Alterations in gas exchange during OLV were minimal. Prolonged collapse of the lung with subsequent reexpansion was associated with a slight decrease in compliance, indicating some mild lung injury.

Animals↗
PubMed1998

Evaluation of filling materials in membrane--protected bone defects. A comparative histomorphometric study in the mandible of miniature pigs.

In recent years, bone grafts and bone substitutes have been increasingly utilized underneath barrier membranes to optimize the treatment outcome of bone reconstructive therapy for defects in the alveolar process. In the present study, 4 different filling materials were evaluated in bone defects of similar dimensions in the mandible of miniature pigs. Blood clots and autografts were used as controls. The defects were covered with barrier membranes and allowed to heal for 4, 12 or 24 weeks. Histologic examination demonstrated that bone repair progressed through a programmed sequence of maturation steps closely resembling the pattern of bone development and growth regardless of whether bone grafts or substitutes were present or not. Histomorphometric analysis showed that autologous bone grafts (autografts) had the best osteoconductive properties during the initial healing period, with 39% of newly formed bone inside the membrane-covered defects at 4 weeks of healing. In addition, 87% of the graft surfaces were already covered by bone at this time. Both values were significantly higher for autografts than for the 4 alternative bone fillers (P < or = 0.05). At 12 weeks, these differences were no longer apparent, with all 5 filling materials showing similar values. Among the tested bone substitutes, tricalcium phosphate (TCP) showed a significantly higher percentage of bone fill at 24 weeks of healing. It can be concluded that sites filled with autografts clearly demonstrated the best results underneath barrier membranes in the early phase of healing. As far as degradation and substitution are concerned, TCP showed the most promising results. This filler, however, needs to be tested further in a more demanding animal model. Less favorable results were obtained for coral-derived hydroxyapatite granules and for demineralized freeze-dried bone allografts.

Alveolar Bone Loss↗
PubMed1998

Left heart bypass in the pig with a centrifugal pump using cannulae prepared for percutaneous placement.

A rapid and efficient circulatory support system may save a patient in cardiogenic shock. Left heart bypass with percutaneous and trans-septal placement of the aspiration cannula simplifies the circuit and eliminates the need for an oxygenator. In this pre-clinical study we assessed left heart bypass support with a centrifugal pump using new cannulae prepared for percutaneous placement (14 F arterial catheter and 16 F left atrial aspiration line) in 5 anaesthetized pigs. Animals were supported for two hours at a mean flow of 3.2 l/min (4,033 rpm), a mean haematocrit of 29% and low heparinisation (ACT double baseline). Hemodynamic measurements and blood samples were taken at baseline (A), 10 minutes (B), one hour (C) and 2 hours (D) on support. Results show maintenance of hemodynamic parameters throughout the 2 hour support period. Only systolic arterial and left ventricular pressure decreased by 12% and 20% respectively from baseline to the end of the support period with a 13% increase in cardiac output. When the pump was turned on (0-3 l/min) there was usually a decrease in heart rate, systolic pressure and left ventricular pressure, with unchanged cardiac output (non failing model). Potassium increased from 3.9 to 4.2 mmol/l (ns), and plasma hemoglobin from 6.0 to 18.2 mg/dl (p<0.05). Thrombocytes decreased from 187 to 155 10(9)/l (ns). In conclusion, this preclinical study demonstrated the feasibility of an efficient left heart bypass of short duration with a centrifugal pump using cannulae prepared for percutaneous placement. Left heart bypass was well tolerated hemodynamically and no significant laboratory change occurred within the two hours of support. This opens several possibilities for the short term support of patients in cardiogenic shock and eventually also for patients submitted to minimally invasive cardiac surgery.

Animals↗
PubMed1997

VATS-guided epicardial pacemaker implantation. Hand-sutured fixation of atrioventricular leads in an experimental setting.

BACKGROUND: In neonates and infants epicardial stimulation may be preferred to endocardial stimulation because of growth-associated lead problems and the risk of vascular complications associated with transvenous electrodes. This study analyzes the feasibility of atrioventricular implantation of a new epicardial lead using the video-assisted thoracic surgical (VATS) technique in an animal model. METHODS: Bipolar steroid-eluting epicardial leads were implanted in seven young white pigs. In five animals bipolar atrial and ventricular pacing leads (n = 10) were inserted and fixed by the VATS technique, while two animals served as controls and underwent implantation through anterolateral thoracotomy. Surgical feasibility, pacing, and sensing thresholds of the leads as well as hemodynamic parameters during pacing were studied. Histological changes beneath the electrodes were evaluated 1 week after the implantation. RESULTS: All animals survived the pacemaker lead implantation. One animal which underwent thoracotomy died because of irreversible ventricular fibrillation induced by rapid ventricular pacing. One animal in the VATS group exhibited intraoperative herniation of the heart through the pericardial window. All animals with left-sided VATS implantations demonstrated good individual pacing and sensing threshold values. The mean cardiac output was 1.6 times higher during AAI-mode pacing as compared to VVI-mode pacing at a heart rate of 140/min. One animal died postoperatively due to respiratory failure. No displacements of the pacemaker leads were observed in the survivors. CONCLUSION: While VATS-guided implantation of epicardial, atrial, and ventricular leads is feasible, technical improvements of the system are mandatory for safe clinical application.

Animals↗
PubMed1997

Experimental assessment of photodynamic therapy with chlorins for malignant mesothelioma.

OBJECTIVE: Photodynamic therapy (PDT) with two chlorin sensitisers was assessed on nude mice bearing human mesothelioma xenografts, and on intrathoracic tissues of minipigs with the same drug-light conditions to optimise the antitumour activity of PDT while preventing photosensitising injury to normal tissues. METHODS: Laser light (20 J/cm2) at 652 nm was delivered to the xenografts 1-4 days after i.p. administration of 0.1 mg/kg m-tetrahydroxyphenyl-chlorin (mTHPC) or an equimolar dose of polyethylene glycol-derived mTHPC (pegylated mTHPC), respectively. The extent of tumour necrosis was assessed by histomorphometry. Intraoperative PDT was then performed to the thoracic cavity of minipigs through a sternotomy with the same drug-light conditions at drug-light intervals ranging from 12 h to 6 days after i.v. administration of mTHPC and pegylated mTHPC, respectively. RESULTS: Both, mTHPC and pegylated mTHPC, resulted in photosensitised necrosis of mesothelioma xenografts at drug-light intervals from 1 to 4 days but the extent of necrosis was significantly larger by use of pegylated mTHPC instead of mTHPC at a drug-light interval of 3 and 4 days. The optimal tumourcidal effect was achieved with pegylated mTHPC at a drug-light interval of 4 days. The photosensitising effect of mTHPC on intrathoracic tissues of minipigs revealed severe damage of virtually all tissues except nerves at short drug-light intervals. Tissue damage gradually became less at longer drug-light intervals and was absent at intervals of 3 days and longer. In contrast, pegylated mTHPC resulted in no obvious change to any structure at any drug-light interval assessed. CONCLUSIONS: PDT with pegylated mTHPC reveals the potential of selective tumour destruction in this experimental setting and deserves further evaluation for intraoperative application in patients with malignant mesothelioma.

Animals↗
PubMed1997

Effects of one-lung ventilation on pulmonary hemodynamics and gas exchange in the newborn.

For major thoracoscopic surgery, one-lung ventilation is mandatory. This is reasonably well tolerated in adults and children. The effects of one-lung ventilation on hemodynamics and gas exchange in newborns, however, are not known yet. Eight neonatal domestic pigs with a median age of 6 days (range: 3-9 days), and a mean body weight of 2.3 kg (1.7-2.8 kg) were intubated and ventilated in pressure-controlled mode (FIO2 = 1). Anesthesia was maintained with i.v. fentanyl/metomidate. After tracheotomy an endotracheal tube was positioned in the trachea, and a second tube in the left mainstem bronchus. One-lung ventilation was maintained for 120 min. Serial measurements were done before, during, and until 90 min. after one-lung ventilation. During one-lung ventilation, pulmonary artery pressure and intrapulmonary shunt increased from 15 +/- 1 to 18 +/- 1 mmHg (p = 0.004), and from 2.6 +/- 0.3 to 3.7 +/- 0.4% (p = 0.02), respectively. Arterial oxygen saturation remained unchanged at 100%. A slight increase in arterial PCO2 could easily be treated by increasing the respiratory rate. In conclusion, one-lung ventilation was not associated with major side effects in regard to hemodynamics and gas exchange in the neonatal pig.

Adult↗
PubMed1996

Video-assisted mediastinal lymph node dissection assessed in an experimental setting.

BACKGROUND: Feasibility, completeness, and morbidity of videoscopic-assisted mediastinal lymph node dissection (VATS MLND) were compared to the standard surgical technique in an experimental study. METHODS: Right upper MLND--together with upper lobectomy in half of the cases--was performed in ten large white pigs. Six animals were operated using VATS (group 1), four using conventional open techniques (group 2). After 1 week, the animals were sacrificed and the mediastinum was assessed for remaining lymph nodes. RESULTS: All animals survived without intra- or post-operative complications. There was no significant difference in the operation time between the two groups (3.2 +/- 0.8 vs 3.2 +/- 0.2 h). The number of mediastinal lymph nodes harvested was 9.5 +/- 2.7 in group 1 and 11.5 +/- 0.5 in group 2 (n.s.). The post-mortem assessment of the mediastinum showed in two animals of group 1 and in two animals of group 2 that one lymph node was left behind. In addition, in one animal of group 1 four small retrotracheal lymph nodes were found. CONCLUSIONS: VATS MLND can be accomplished without morbidity and is as radical as that achieved with conventional surgery in the paratracheal and peribronchial areas in this experimental setting. However, retrotracheal lymph node dissection might not be as complete as achieved by conventional surgery.

Animals↗
PubMed1995

Renal pathology after arterial yttrium-90 microsphere administration in pigs. A model for superselective radioembolization therapy.

RATIONALE AND OBJECTIVES: To test the selectivity of tissue damage in radioembolization, the authors performed an experimental study using superselective administration of yttrium-90 particles to deliver up to 100 Gy to the porcine kidney. Patterns and severity of damage in test organs were compared with controls, and the feasibility of this model is discussed. METHODS: Eight sows were included in the study. Bio-Rex 70 particles were applied via selective catheterization of the renal artery. Four pigs received inactive particles and four pigs received active particles. Organ distribution and shunting of yttrium-90 were determined, and kidney damage patterns were histologically analyzed. RESULTS AND CONCLUSIONS: The model demonstrates that yttrium-90-labeled resin particles can superselectively be applied. Retention of beta activity in the target organ was more than 95%. In addition to tissue shrinkage from mechanical obstruction, considerable damage ensued mainly by radiation-induced arterial necrosis and arteritis.

Animals↗