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Biomedical subjects

H Siegl

Publications and source records attributed to H Siegl.

At least 19 recordsLinked to original sources

Recorticalization after bifocal internal bone transport in the double-plated sheep femur.

Distraction osteogenesis and bone remodelling after the end of bone transport were investigated in one femur each of six adult male sheep. A newly designed internal distraction device was used. A custom-made osteosynthesis plate was fixed on the lateral side of the femur, and two transporting plates driven by a transcutaneously inserted screwdriver moved two bone cylinders simultaneously over a 40 mm defect. An additional plate was applied ventrally to stabilize the device. Bone transport was begun 2 weeks postoperatively at 1 mm/day at each transporting plate until they came into contact. New bone formation within the distraction gaps was evaluated by computed tomography scans and was quantified at 4 and 6 months by dual energy x-ray absorptiometry as well as histomorphometry on polyfluorochrome-labelled undecalcified ground sections and microradiographs. At 4 months, all distraction gaps were bridged by abundant newly formed bone trabeculae, which were reduced and condensed to cortex-like layers of new bone at 6 months. Less new bone was always found under the lateral device than in the unplated medical and dorsal segments, but the amount of new bone under the ventral plate was comparable with that in the unplated regions. The results of this pilot study show that distraction osteogenesis can be achieved with an internal device such as this one and that recorticalization and restoration of a medullary canal occur despite the relatively rigid internal stabilization by the plates.

Animals

A physical analog of the failing left ventricle for in vitro studies of mechanical wall actuation.

Mechanical repowering of a failing heart with devices or skeletal muscle could circumvent blood-pump lining problems. Requirements are complex: indefinite support with preservation of valve competence and coronary flow, avoidance of wall coaptation, and allowance of both rapid low impedance refilling and independent left and right pressures. An accurate in vitro physical failing-heart analog could facilitate the choice and screening of surgical and engineering approaches in mock circulation experiments. Prosthetic models, transplant recipient hearts, normal animal hearts, existing in vivo animal failure models, and failing cadaver hearts all have serious limitations. One hundred and four excised porcine hearts were dilated and fixed by three iterative protocols. Geometric and passive mechanical parameters were assessed and compared with targets expected for an end-stage failing heart. For Protocol 3, Subgroup 2 (reinforcing valve support, dilatation by compliant ventricular balloon, and ethyl alcohol fixation), the left ventricular shape and capacity (ellipsoid, 201-377 ml/500 g of heart weight), passive valve function, wall flexural rigidity (Et3 range 0.101-0.331 Nm), and refilling mechanics (99 +/- 17.46 ml during 200-400 ms at < or = 10 mm Hg transmural gradient) were all within goal criteria.

Animals

Intraperitoneal cholelithiasis after laparoscopic cholecystectomy--behavior of 'lost' concrements and their role in abscess formation.

UNLABELLED: In two experimental studies we sought preliminary information about the behavior of concrements lost in the peritoneal cavity during laparoscopic cholecystectomy. MATERIALS AND METHODS: In study 1, human gallstones were analyzed using X-ray diffraction, classified in three groups and examined with an ultramicroscope; then they were implanted in the peritoneal cavity of rats. After 8 weeks or 6 months, the animals were sacrificed and the concrements analyzed again as before. The tissues surrounding the calculi were also examined histologically. In study 2, human gallstones were examined with regard to bacterial contamination on the surface or in the middle of the calculi. The cholesterol content was analyzed, and the stones were divided into three groups and implantated in the rats as in the first study. After 8 weeks, the animals were sacrificed and areas with identifiable tissue reactions were examined histologically and microbiologically. RESULTS: The concrements lost their crystalline formation without any relation to their former cholesterol content, as shown by X-ray diffraction as well as ultramicroscopy. Mineralogically, these changes are a certain sign of structural dissolution. Cholesterol stones only caused abscess formations in association with gram-negative bowel germs. Sterile pigment concrements often led to a mesenchymal reaction such as granulomas. Contaminated pigment stones also resulted in extensive abscess formations.

Abscess

Effect of bone cylinder length on distraction osteogenesis in the rabbit tibia.

The viability and osteogenic potential of bone cylinders for bone transport was investigated in one tibia of 18 mature male New Zealand rabbits. The length of the bone cylinder was equal to or twice that of the diameter of the tibia. The cylinder was cut subperiosteally with an externally cooled oscillating saw from a lateral approach, after a specific unilateral external fixator had been applied. To simulate bone transport, one end of the cylinder was fixed to the distal bone stump by a cerclage wire and healing and revascularization was prevented by an interposed expanded polytetrafluoroethylene membrane. The periosteum was re-adapted and sutured, and distraction began 10 days postoperatively at 0.25 mm/12 hours for 22 days. New bone formation in the distraction gap was quantified by dual energy x-ray absorptiometry and by computer-assisted histomorphometry of polyfluorochrome-labeled undecalcified bone sections and corresponding microradiographs. In half of the animals with each size cylinder, osseous bridging occurred, so the findings on distraction osteogenesis are reported only for the remaining nine animals. Generally, centripetal mineralization of the gap with two distinct zones of ripening bone structures and a central radiolucent fibrocartilaginous zone could be distinguished. Neither absorptiometry nor histomorphometry showed significant differences in the overall amount of this new bone formation for the bone cylinders of two different lengths. However, osteogenesis was significantly greater at the proximal end than at the cylinder. New bone was formed predominantly from endosteal sites in the smaller cylinders and from periosteal sites in the larger cylinders. Histologically, there was complete necrosis of both sizes of cylinders, followed by revitalization through newly formed vascular channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Absorptiometry, Photon

Hemodynamic effects of prolonged abdominal insufflation for laparoscopic procedures.

Abdominal insufflation for laparoscopic procedures leads to numerous hemodynamic effects. We focused on blood flow distribution and arterial and venous pressure changes during CO2 insufflation at an intra-abdominal pressure of 12 mm Hg. Three segments of the vascular system were investigated (intrathoracic, cranial extrathoracic, caudal extrathoracic) in supine animals at insufflation, during a 90-minute period of pneumoperitoneum, and at desufflation. Except for instrumentation of the animals, no further surgery was performed. At insufflation (+5 minutes), cardiac output increased from 2.7 +/- 0.5 to 3.3 +/- 1.1 L/min while heart rate decreased from 138 +/- 26 to 128 +/- 17 beats per minute. Increases in jugular venous (from 6 +/- 1 to 11 +/- 4 mm Hg) and atrial (right, from 7 +/- 1 to 12 +/- 3; left, from 12 +/- 4 to 17 +/- 5 mm Hg) pressures occurred uniformly during inspiration. The great variance in atrial pressures during ventilation was not associated with changes in stroke volume, as the effective transmural filling pressures remained nearly constant. The increase in femoral venous pressure occurring during both inspiration and expiration (from 10 +/- 2 to 18 +/- 4 mm Hg) exceeded the increase in right atrial and jugular venous pressures during inspiration. Parallel increases were noted in arterial pressures (carotid, from 119 +/- 15 to 129 +/- 9; femoral, from 122 +/- 16 to 133 +/- 10 mm Hg), left ventricular pressure (from 133 +/- 17 to 143 +/- 10 mm Hg), and carotid and femoral flow (carotid, from 174 +/- 71 to 195 +/- 70; femoral, from 66 +/- 25 to 73 +/- 40 (NS) mL/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

[Educational opportunities in minimally invasive surgery].

Since minimally invasive surgery makes high demands on the skill, concentration and endurance of the surgeon, requisite training in this operating technique is of overriding importance. Basic training on pelvitrainers serves to enable the participant to become acquainted with the instruments and the video technique and to gain experience in handling the camera. A realistic simulation of intraoperative situations is not possible. With pulsatile organ perfusion (POP) nearly all abdominal, thoracic, vascular, urological and gynecological surgical procedures, as well as the encountered complications, can be imitated, widely replacing the need for animal experiments. Complex operations which are bound to anatomical structures, have to be practised on anaesthetized animals, as before.

Animals

The Vienna implantable centrifugal blood pump.

Because of the inherent disadvantages of membrane pumps, rotary pumps have been increasingly investigated in recent years. As a result of improving biocompatibility, extended assistance with implantable devices is of special interest. Questions arise concerning shear stress, blood traumatization, design of seals, and specific control conditions. In their development of an implantable impeller pump, the Vienna group studied the minimization of hemolysis and thrombus formation by means of numerical simulation, visualization, and in vitro blood evaluation. The latter was revealed to be the most powerful tool for pump evaluation. With optimization of geometry, a hemolysis of in vitro: IH = 0.008; MIH = 0.58; and in vivo: 2.1 to 3 mg% plasma-free hemoglobin could be obtained. For proper control and physiological adaptation, a controller based on a nonlinear and a fuzzy strategy was developed. Furthermore, a method for evaluation of the contractility of the assisted heart during nonpulsatile support was tested by computer simulation. This paper summarizes the evaluation methods used and provide an overview of the results of pump and controller design.

Animals

Hemodynamic changes during prolonged laparoscopic surgery.

7 healthy pigs, anesthetized with ketamine/azaperon/thiopentone and ventilated with O2/N2O by volume control, underwent anterior resection of the descending colon by laparoscopic view. During operation of pneumoperitoneum by inflating CO2 to an abdominal pressure of 14 mm Hg was installed. Immediately (+2 min) after the onset of insufflation, both systemic and pulmonary arterial pressure increased. However, pulmonary artery pressure started to decrease after 10 min, whereas systemic arterial pressure remained elevated until the end of the experimental protocol. Left ventricular (LV) pressure and LV dp/dt increased in parallel with the systemic arterial pressure. Peak inspiratory pressure and central venous pressure increased in parallel with the abdominal pressure. Blood gas analysis of arterial and pulmonary blood demonstrated increased pCO2 associated with mild acidosis. Arterial pO2 did not change significantly indicating that the decreased pulmonary distensibility did not endanger the oxygenation. Pulmonary pO2 and pulmonary O2 saturation increased early (+10 min) after start of insufflation and were stable during the 2 h of observation indicating either increased cardiac output or decreased O2 extraction. We conclude that the sharp initial rise of both arterial pressures could be the effect of a mechanical action, whereas sustained hemodynamic alterations would involve complex regulatory mechanisms like an increase of sympathetic activity, baroreceptor control, or a response to acidosis. The acute and, in the systemic circulation, stable increase of ventricular afterload should be considered in patients with underlying cardiac diseases such as ischemic heart disease or valvular dysfunction or in patients taking drugs which interfere with normal compensatory processes.

Animals

SDZ 216-525, a selective and potent 5-HT1A receptor antagonist.

The pharmacological properties of SDZ 216-525, methyl 4-(4-[4-(1,1,3-trioxo-2H-1,2-benzoisothiazol-2-yl)butyl]-1-p iperazinyl)1H- indole-2-carboxylate, a new selective and potent 5-HT1A receptor antagonist, are described in vitro (and comparisons made with those of MDL 73005 and NAN 190, two putative 5-HT1A receptor antagonists) and in vivo. In radioligand binding studies, SDZ 216-525 showed high affinity and selectivity for 5-HT1A sites (pKD = 9.2) as compared to 5-HT1B, 5-HT1C, 5-HT1D, 5-HT2 and 5-HT3 sites (pKD = 6.0, 7.2, 7.5, 5.2 and 5.4, respectively). The affinity of the compound for alpha 1, alpha 2, beta 1 and beta 2 adrenoceptors, and dopamine D2 receptors was at least 50-100 times lower than for 5-HT1A sites. The effects of SDZ 216-525, MDL 73005 and NAN 190 on 5-HT1 receptor-linked second messengers were characterised in the following tests: inhibition of forskolin-stimulated adenylate cyclase activity in calf hippocampus (5-HT1A), rat substantia nigra (5-HT1B) and calf substantia nigra (5-HT1D) and stimulation of inositol phosphate production in pig choroid plexus (5-HT1C). SDZ 216-525 potently antagonised the effects of 8-OH-DPAT (8-hydroxy-2-[N-dipropyl-amino]-tetralin) on 5-HT1A receptors (pKB = 10) and displayed no intrinsic activity in this test, whereas it behaved at best as a weak antagonist on the other receptor models (pKB values < 6.9).(ABSTRACT TRUNCATED AT 250 WORDS)

8-Hydroxy-2-(di-n-propylamino)tetralin

In vitro investigation of thrombogenesis in rotary blood pumps.

Thrombus formation at sealing and stagnation areas remains a major problem in the development of rotary blood pumps. Until now, the complex phenomena could only be studied in vivo. In this study, an in vitro mock circulation previously used for hemolysis studies was adapted for thrombosis evaluation. Blood was collected in the slaughterhouse with strict avoidance of air contact and was heparinized (1.5 U heparin/ml blood; activated coagulation time [ACT]: initially, 140-180 s; after collection, 400-600 s). During the test, the ACT decreased gradually. The tests were stopped after 90 to 180 min at an ACT of 1.5 times the initial value. Thrombus formation was observed at the same locations as observed in left-heart assist devices (sealing area, connecting bolts, and stagnant water areas at connectors). The thrombi were similar in shape, color, and histology to those found after 2 to 4 days in vivo. This test provides a valuable tool for evaluating thrombus formation in prototypes and screening tests of different rotary pump designs.

Animals

[Laparoscopic colon surgery--from experiment to initial clinical experience].

The technique of Laparoscopic resection of the colon sigmoideum was practised in an experimental model before starting a clinical program of laparoscopic colonic surgery. Until now, two resections of the colon sigmoideum, one ileocecal resection, one right colectomy, one Hartmann's procedure and one transversostomy have been performed laparoscopically. Three patients had colonic carcinoma. One sigmoid resection had to be converted to open surgery and this patient underwent relaparotomy because of postoperative ileus. The postoperative course of the other patients was uncomplicated. The promising initial experience demonstrates that laparoscopic colonic surgery is feasible, although further studies have to prove advantages and indications, especially with respect to oncology.

Adolescent

Improved endothelialization of postfixation treated biological vascular grafts.

Preliminary in vitro and in vivo studies have shown that endothelialization is improved by a detoxifying postfixation treatment of glutaraldehyde (GA) fixed bovine pericardial patches and grafts. To test whether this is also true for GA tanned human vein (HUV) grafts, patches of commercially available HUV grafts (MHUV), postfixation treated HUV grafts (PTHUV) and GA fixed HUV granfts (GAHUV) were endothelialized in vitro. Eight pairs of MHUV and PTHUV grafts were implanted as femoropopliteal grafts in eight sheep. Endothelial cell adherence was significantly better on PTHUV (11910 +/- 4413 cells/cm2) than on MHUV (6545 +/- 2835 cells/mm2; p = 0.0007) and on GAHUV (3563 +/- 1638; p = 0.0001) one day after cell seeding. After eight days of culture significantly more cells spread on PTHUV material than on MHUV (p = 0.0002), but none of the cultures on GAHUV remained viable. Four PTHUV grafts occluded in the femoropopliteal position, mostly because of kinking, so that only in four pairs of grafts could the thrombus-free surface be compared by planimetry. Again PTHUV material was covered more by endothelial cells than was MHUV material. On PTHUV endothelial cells spread directly on the graft material while on MHUV these cells spread on a layer of fibrin and macrophages. Postfixation treatment of GA-fixed biological graft material by amino-acid solutions improves the biocompatibility of the material and enhances in vitro as well as spontaneous in vivo endothelialization.

Animals

Alpha and beta-adrenoceptors in hypertension. I. Cardiac and renal alpha 1-, beta 1-, and beta 2-adrenoceptors in rat models of acquired hypertension.

To determine whether adrenoceptor changes in genetic hypertension occur primary or secondary to blood pressure elevation, we measured cardiac and renal alpha 1- (by [125I]Be 2254 binding) and beta 1- and beta 2-adrenoceptors (by (-)-[125I]iodocyanopindolol binding) densities in various rat models of acquired hypertension (Dahl S rats on a high-sodium diet, 1-clip-1-kidney (1C-1K) renal hypertensive and DOCA-salt hypertensive rats) in comparison with genetically identical age-matched untreated rats. In addition, alpha 1-adrenoceptors were assessed in spontaneously hypertensive rats (SHR) and in SHR treated with the immunosuppressant cyclosporin A. In heart, no clear pattern of changes in alpha 1- or beta 1- and beta 2-adrenoceptors was obtained. In kidney, however, beta 1- and beta 2-adrenoceptors were increased in all models of hypertension, and a good correlation between renal beta-adrenoceptors and systolic blood pressure was found. In contrast, renal alpha 1-adrenoceptors were only increased in SHR but not in any form of acquired hypertension. Thus, renal beta-adrenoceptor increases probably occur secondary to blood pressure elevation, whereas alpha 1-adrenoceptor increases appear to be associated with genetic hypertension. Because renal alpha-adrenoceptors are linked to tubular sodium reabsorption, we suggest that an increase in renal alpha 1- (and alpha 2)-adrenoceptors may be a very early step in the development of genetic hypertension.

Animals

Diffusion characteristics dissociate ouabain binding from inotropic effect in guinea-pig myocardium.

1. [3H]-ouabain uptake in resting guinea-pig papillary muscles depended directly on incubation time and inversely with muscle radius. The equivalence of both parameters support the relevance of diffusion. A particular mechanism of receptor-controlled diffusion was implicated by the saturation of initial rates of uptake with increasing ouabain concentrations. Saturation of initial uptake indicates an inhomogeneity of receptor occupancy with ouabain-equilibrated receptors in the superficial areas of the preparation and free receptors in the muscle core. 2. For comparison [3H]-ouabain diffusion was evaluated in a non-cellular preparation i.e. glass fibre filters soaked with modified Krebs-Henseleit solution. Diffusion was approximately 3 orders of magnitude faster when compared with the papillary muscles. 3. The time course of the inotropic effect of ouabain on rested-state contractions dissociated from the tissue content of ouabain with an increased steroid concentration. This dissociation appears to be associated with the inhomogeneity of receptor occupancy, since equal amounts of the steroid correspond to different concentration profiles in the tissue when the bath concentration is changed. Functional coupling between different muscle areas may have modulated the influence of inhomogeneous receptor occupancy.

Animals

Selective effects of PN 200-110 (isradipine) on the peripheral circulation and the heart.

PN 200-110 (isradipine) is a new dihydropyridine calcium antagonist with selective actions on the heart as well as the peripheral circulation. It selectively inhibits the sinus node but not atrioventricular conduction and its negative inotropic action is minimal, about 20 times weaker than its negative chronotropic effect. This in vitro pattern also expresses itself in vivo: partial suppression of the reflex tachycardia induced by its peripheral vasodilatation and no effect on the P-Q interval on the electrocardiogram even at large doses. The presence of first- or second-degree heart block should therefore not limit its use, whereas the sick sinus syndrome might. PN 200-110 does not decrease myocardial contractile force even in vagotomized animals with full beta blockade. PN 200-110 nevertheless lowers myocardial oxygen consumption mainly by its action on afterload. It should therefore be useful in angina pectoris. PN 200-110 is a powerful peripheral vasodilator. It preferentially dilates coronary, cerebral and skeletal muscle vasculature. Its long lasting (24 to 48 hours) antihypertensive action is not accompanied by tachycardia in spontaneously hypertensive rats and it enhances sodium and water excretion in normotensive rats. It should be useful in the treatment of hypertension, and, considering its pattern of cardiac actions, perhaps also as an after-load-reducing agent for the treatment of heart failure. Antiarteriosclerotic effects in conscious rabbits were found at reasonably small doses, suggesting that such effects might occur in man at therapeutic doses.

Animals

Frequent stimulation of the guinea-pig myocardium raises the inotropic efficacy of tissue-bound ouabain.

3H-Ouabain binding to frequently (1 Hz) stimulated papillary muscles from reserpine-pretreated guinea pigs was evaluated at ouabain concentrations of 18.5 and 200 nmol/l. Myocardial activity increased the amount of 3H-ouabain bound to the tissue in comparison with quiescent preparations. Since the shape of the time course of ouabain binding changed with frequent stimulation, a greater number of ouabain-accessible binding sites of the Na pump as induced by the rise in intracellular Na with frequent stimulation cannot be the sole mechanism of the frequency dependence. In view of their stimulatory properties on the Na pump the effects of intracellular Na and extracellular K could be equivalent. By contrast, both interventions were differently effective. The K antagonism on 3H-ouabain binding was independent from stimulation frequency. Furthermore, the shape of the time course of binding was not altered by [K]o. As evidenced by the dependence of half-times to steady-state effect on muscle diameter, the apparent rate of diffusion of ouabain was accelerated with the frequency of contractions. This acceleration could have interfered with the time course of binding at frequent stimulation. After correlating the time courses of positive inotropic effect and ouabain binding (concentration of ouabain in the medium 200 nmol/l), frequent stimulation was found to raise the inotropic efficacy of tissue-bound ouabain. The relation of excitation-dependent Na influx to the saturable, ouabain-inhibited, Na pump explained the frequency dependence of the intropic efficacy of ouabain; that is, the observed change of efficacy was consistent with Na-pump saturation in dependence on intracellular Na.

Animals

Nephrotoxicity of cyclosporine in spontaneously hypertensive rats: effects on blood pressure and vascular lesions.

Cyclosporine (CSA) caused functional and morphologic renal changes in spontaneously hypertensive rats. The development of hypertensive arterial lesions were accelerated by CSA. Blood pressure was significantly increased especially in young rats. The influence of age of the animals, dose and duration of CSA administration on the development of vascular lesions and blood pressure was investigated.

Animals

Renal and antihypertensive effects of co-dergocrine (Hydergine) in rats.

The renal actions of co-dergocrine and its components (DH-ergocornine, DH-beta-ergokryptine, DH-alpha-ergokryptine and DH-ergocristine) were studied in conscious normotensive and spontaneously hypertensive (SH-) rats. Following p.o. and s.c. administration, co-dergocrine and its components induced dose-dependent increases in water and sodium chloride excretion in both strains. Changes in urinary excretion of potassium were small. Concomitantly, in SHR, blood pressure (BP) and heart rate (HR) were decreased. In both strains the salidiuretic activity of co-dergocrine remained relatively constant following prolonged administration. In addition in SHR basal plasma renin activity (PRA) as well as BP and HR were decreased. Experiments were also performed in order to investigate the mechanisms underlying the renal effects of co-dergocrine.

Adrenalectomy