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Biomedical subjects

G Hellige

Publications and source records attributed to G Hellige.

At least 37 records · Page 2Linked to original sources

Development and initial in vivo testing of a new hydraulic drive system (Paedipump) for circulatory support in infants.

The main limitation in the use of circulatory support in children is the lack of an adequate system with regard to size and pumping capacity. Recently, two pneumatically driven ventricular support systems with low volume chambers for use in a pediatric population became available. We have developed a hydraulic drive system with an advantageous exact control of the stroke volume. The system enables two different modes of operation: the full-empty and the filled-empty modes. In both cases the ventricle is empty at the end of systole. This new system was tested in experimental animals (6 pigs, body weight 9.5-14.0 kg) with normal and reduced left ventricular function (MAP<45 mmHg). A 25 ml ventricle (HIA-Medos) was implanted. The full-empty and the filled-empty mode used led to a significant load reduction, both in animals with normal and impaired cardiac function. Plasma lactate levels, pH-values and total body O2-consumption were in the normal range during circulatory support indicating adequate organ perfusion. Results showed that sufficient ventricular support was achieved during all pumping modes due to the possibility of controlling and modifying the stroke volume of the hydraulically driven support system employed according to necessity. This is a promising feature for its future application in infants with congenital or acquired heart diseases.

Animals↗

Influence of high-dose ketamine on the vascular reactivity of human and porcine isolated coronary artery segments.

The influence of ketamine on the vasomotor effect of histamine and serotonin was studied in isolated human and porcine coronary artery rings. Ketamine (10(-3) mol L-1) attenuated the contractile response to both mediators significantly (P < 0.05 for histamine concentrations of 3 x 10(-5) mol L-1 and above as well as for serotonin concentrations of 3 x 10(-8) mol L-1 and above). This effect of ketamine was observed in intact and endothelial denuded porcine rings (difference n.s.) as well as in coronary arteries from explanted human hearts of patients undergoing heart transplantation. It is concluded that this reduction of the contractile response to histamine and serotonin caused by ketamine is not dependent on the endothelial function (e.g. endothelium-derived relaxing factor).

Anesthetics, Dissociative↗

Modelling of non-linear pharmacokinetics in sheep after short-term infusion of cardiotoxic doses of imipramine.

Imipramine was administered to sheep (n = 10) by intravenous infusion in high doses (450 mg-900 mg) to elicit cardiovascular shock. A cardiac assist device was then employed to manage the acute overdose situation. The concentration-time course of imipramine and its metabolite desmethylimipramine in plasma was measured by HPLC. As an indicator of imipramine's cardiotoxic effect, cardiac output was monitored. The aim of the study was to evaluate the pharmacokinetics under these conditions and to assess the efficiency of a cardiac assist device with (n = 5) and without (n = 5) an integrated haemoperfusion unit in removing drug from the circulation. The kinetics of imipramine could be described by a three compartment body model with concentration-dependent clearance resulting in non-linear kinetics. The changes in cardiac output with time could be linked to the pharmacokinetic model by a linear relationship. The cardiac assist device was found to contribute to the overall elimination of imipramine whereas the haemoperfusion unit had no clinically relevant impact.

Animals↗

[LOGNORMAL-NLSQ-technique. Evaluation of a new mathematical method for determining blood volume].

This paper describes the investigation of a new mathematical method of calculating blood volume. The new method determines the blood volume by calculating the product of the mean circulation transit time. The mean transit time is calculated from the body transport function. To examine the accuracy of the LOGNORMAL-NLSQ technique, 45 concentration time curves were measured in an in vitro recirculation model with variable clearance. The calculated volume was 4% smaller than the actual volume. This may be attributed to the functional dead space within the model, and is tolerable for clinical situations. The LOGNORMAL-NLSQ technique might acquire considerable importance in future, especially since it provides accurate results very quickly.

Blood Flow Velocity↗

Gravity-dependent phenomena in lung ventilation determined by functional EIT.

Gravity exerts an effect on the distribution of intrapulmonary ventilation. A study on the detection of gravity-dependent inhomogeneity of ventilation by a functional EIT technique is presented. The study was performed on five human subjects, whose ventilation distribution was modified by changes in body position. The subjects were studied during spontaneous tidal breathing. The qualitative and quantitative analysis of the functional EIT images revealed that the ventilation is higher in the dependent lung regions when compared with the non-dependent ones. These EIT findings correspond to current knowledge of the physiological behaviour of the lungs as derived from the radioactive-gas methods and raise the possibility of applying the less complicated functional EIT in future studies on ventilation distribution in the lungs. This may be of major interest in the monitoring of intensive care patients with severe pulmonary disorders.

Adult↗

Local mechanics of the lung tissue determined by functional EIT.

A new functional EIT (f-EIT) evaluation technique providing information on the local dynamic behaviour of the lung is presented. Out of a series of single EIT thoracic images local time courses of the impedance change are extracted. To detect regional differences in the dynamic behaviour of the lung tissue the local time courses at different locations are related to the average time course of the impedance change over the whole thoracic cross section. The time shifts between this reference signal and the signals from separate positions are calculated from the phase information of the complex cross spectra and evaluated in terms of the local phase angle. The computed phaseshifts are imaged over the cross section creating an 'f-EIT phase image' characterizing the local dynamic properties. To relate the observed differences to the proper lung location the resulting images are presented as a combination of the f-EIT ventilation images, which represent the local amplitude of ventilation and the f-EIT phase images. The new imaging technique was tested in spontaneously breathing humans. Alterations to pulmonary dynamics were induced by changing the body posture of the subjects. The f-EIT phase imaging procedure was shown to identify lung regions with different dynamics and it is expected that this technique will also distinguish pathologically determined alterations.

Biomechanical Phenomena↗

Myocardial extraction of bupivacaine in anaesthetized sheep and by hearts of sheep and rats in vitro.

We observed the in vivo kinetics of bupivacaine in the cardiopulmonary system, particularly in the pulmonary artery, the upper part of the descending aorta and the coronary sinus of anaesthetized sheep, each of which received a high dose infusion into the central vein. In some experiments dilution curves were monitored for the non-extracted dye, indocyanine green. Concentrations of bupivacaine were approximately 20% lower in the aorta than in the pulmonary artery. This gradient of bupivacaine was present across the lung for 5-10 min. Concentrations of bupivacaine in the coronary venous plasma were also markedly lower than at the arterial site. Initially more than 50% of the amount of bupivacaine at the arterial site was removed by the heart. Later, the myocardial extraction ratio decreased and plateaued at a value of 0.30-0.40. At this time, concentrations of bupivacaine in the pulmonary artery were approximately 12 micrograms ml-1. Therefore, approximately 0.3-0.6 mg of bupivacaine were extracted per minute by the sheep heart in vivo. On the other hand, isolated perfused rat hearts did not substantially remove bupivacaine (2 micrograms ml-1) from the medium. Approximately one-third of 14C-bupivacaine was retained in slices of rat and sheep myocardial tissue. However, there was no evidence that metabolism played a substantial role in the cardiac kinetics of bupivacaine.

Anesthetics, Local↗

Pulmonary and left ventricular decompression by artificial pulmonary valve incompetence during percutaneous cardiopulmonary bypass support in cardiac arrest.

BACKGROUND: In cardiac arrest, use of percutaneous cardiopulmonary bypass support (PCPS) may lead to left ventricular loading, with deleterious effects on the myocardium, and is often accompanied by an increase in pulmonary artery pressure. The present study was designed to assess the potential of artificially induced pulmonary valve incompetency to retrogradely decompress the left ventricle during PCPS in ventricular fibrillation. METHODS AND RESULTS: Studies were performed using a standardized experimental animal model in sheep (n = 12; body weight, 77 to 112 kg). When PCPS was used during fibrillation, an increase in left ventricular pressure (from 21.4 +/- 5.0 mm Hg after 1 minute to 28.4 +/- 9.5 mm Hg after 10 minutes of fibrillation) was observed in all animals, with a simultaneous increase in pulmonary artery pressure in 6 animals, from 15.5 +/- 3.8 to 24.3 +/- 5.4 mm Hg (group A). In these animals, artificial pulmonary valve incompetency, which was induced by a special "pulmonary valve spreading catheter," led to effective decompression of both the pulmonary circulation (decrease in pulmonary artery pressure from 24.3 to 11.3 mm Hg) and the left ventricle (decrease in left ventricular pressure from 30.5 to 17.7 mm Hg). We simultaneously measured a decrease in the myocardial release of lactate (increase in arterial coronaryvenous difference in lactate content from -0.01 to 0.14 mmol/L), demonstrating the myocardial protective effect of the procedure. In contrast, in 6 animals without an increase in pulmonary artery pressure during PCPS (group B), artificial pulmonary valve incompetency did not reduce left ventricular loading, which was probably because of competent mitral valves in these animals. CONCLUSIONS: In case of increasing pulmonary artery pressure during PCPS in cardiac arrest, artificial pulmonary valve incompetency might be a useful tool for effective pulmonary and retrograde left ventricular decompression.

Animals↗

[Anesthesia with propanidid in a liposomal preparation. An experimental study in swine].

BACKGROUND: Propanidid was widely used as a short-acting i.v. anaesthetic until it was withdrawn due to severe haemodynamic side effects. It was presumed that anaphylactoid reactions with massive histamine release were caused by the solvent cremophor rather than by propanidid itself. A new liposomal preparation of propanidid was examined in this animal study and compared with propanidid in cremophor solution and with propofol. METHODS: Eighteen pigs were randomly assigned to one of the following groups: Group 1 (n = 6): Propanidid in liposomal preparation (PropaLip; Braun Melsungen, Germany). Anaesthesia was induced with 60 mg/kg, followed by continuous infusion of 400 mg/kg.h. Group 2 (n = 6): Propanidid in cremophor solution (PropaCrem; Sombrevin, Gedeon Richter, Budapest) 15 mg/kg, 100 mg/kg.h. Group 3 (n = 6): Propofol (Disoprivan, Zeneca, Plankstadt, Germany) 5 mg/kg, 20 mg/kg.h. After induction and tracheal intubation, the animals were ventilated with 50% oxygen in air. Basic monitoring included noninvasive blood pressure measurements, electrocardiographic monitoring, and capnography. In a short surgical procedure, arterial and pulmonary artery catheters were placed via the right carotid artery and right internal jugular vein, respectively. As soon as the animals responded to a pain stimulus a second anaesthetic induction was performed, followed by a 60-min continuous infusion of the agent studied with invasive haemodynamic monitoring including arterial and pulmonary arterial pressures and cardiac output. Blood samples were taken for the measurement of serum levels of adrenaline, noradrenaline, cortisol, aldosterone, adrenocorticotropic hormone, and histamine. RESULTS: Intubation conditions and quality of anaesthesia were best in propofol animals, followed by PropaCrem animals. In spite of the large dose of 410 mg/kg.h, resulting in a volume load of as much as 16.4 ml/kg.h, the PropaLip animals showed evidence of poor anaesthetic quality. In group 1 we recorded the highest increases in heart rate (91 vs. 115/min), cardiac output (5.4 vs. 7.7 l/min), plasma catecholamine levels, and histamine concentrations (124-268 ng/ml). CONCLUSIONS: In our animal study, propanidid in liposomal preparation failed to show promise as a new anaesthetic agent. Our results are discussed in view of a drug targeting the cells of the reticuloendothelial system, especially the liver, where liposomes are eliminated from the blood. This may result in the transport of propanidid to one of its major places of inactivation.

Anesthesia, Intravenous↗

[Concomitant hemodynamic effects of intracoronary injections of a new transpulmonary contrast medium].

AIM: A new transpulmonary echo contrast agent (SH U 508) was injected intracoronally to six anaesthetised sheep to examine its possible direct cardiac effects. METHOD: SH U 508 was injected in randomised order in three different volumes (2, 4 and 8 ml; n = 12, 10, 9) with the same drug concentration of 200 mg/ml. RESULTS: The 2 ml and 4 ml injections had no relevant effect on the arterial, pulmonary-arterial and ventricular pressures, on the left ventricular contraction velocity and on the myocardial blood flow (less than +/- 10% of the control value). The left ventricular relaxation velocity decreased by 20%. The disturbance of the left ventricular relaxation at a volume of 8 ml was pronounced (about 40% decrease). Slight left ventricular dysfunction further manifested itself in a decreased systolic pressure (-15%) and increased left ventricular enddiastolic pressure (20%). CONCLUSION: In summary the overall effect of the intracoronary injections of SH U 508 exhibited only minor cardiac side effects. If the current results are extrapolated to peripheral-venous application, the clinically required central-venous 8 ml injection of a 400 mg/ml suspension is not expected to produce any coronary haemodynamic side effects, due to drug dilution in the pulmonary circulation and resulting low intra-coronary concentrations.

Animals↗

Changes in the thoracic impedance distribution under different ventilatory conditions.

The present study was performed with the aim of checking the suitability of EIT in imaging regional thoracic impedance variations during lung ventilation under predefined conditions and to compare EIT with established reference techniques. A new technique of functional EIT imaging designed to visualize physiologically relevant information from the sequentially registered series of thoracic distributions was introduced. Experiments were performed on five spontaneously breathing healthy subjects and on 12 anaesthetized supine pigs. 16 electrodes were placed around the thorax and consecutive transthoracic impedance distributions were measured at a rate of 1 Hz (Sheffield APT system mark I, IBEES, Sheffield, UK). Several voluntary breathing manoeuvres were performed in human subjects and the tracings of local impedance were compared with standard spirometry. In animal experiments EIT was applied during artificial ventilation at different ventilation rates and during stepwise passive emptying and filling of either one or both lungs while the respiratory muscles were relaxes. Further, selective blockade of lung regions resulting in regionally reduced ventilation was performed and the capability of EIT to follow and differentiate local ventilatory disturbances was checked by reference techniques (x-ray and staining methods). The experiments revealed an overall agreement between the spirometric and impedance data in all breathing patterns performed. A linear relationship between changes of the air content of the lungs and the regional thoracic impedance was shown (intraindividual correlation coefficient range, 0.986-0.999; n = 12 animals). The functional images of the impedance distribution across the thorax reproduced adequately the typical anatomical characteristics of the pig and the human thorax. The spatial resolution of EIT functional images was sufficient to differentiate lung areas corresponding to approximately 20 ml tissue volume. EIT with the additional evaluation procedure of functional imaging was shown to be a suitable and reliable method of imaging different ventilatory conditions with the potential to become a useful tool for monitoring respiratory function.

Adult↗

[Interactions between renal and general hemodynamics in fentanyl, droperidol, ketamine, thiopental and in peridural anesthesia--animal studies].

The main focus of this paper is to show regulative interactions between cardiac index (CI) and renal blood flow (RBF) with various intravenous anaesthetics under steady state conditions. Several experimental series were carried out on dogs with the following anaesthetic doses (as given per hour and per kilogram body weight-h-1 x kg-1): fentanyl 50 micrograms, ketamine 4 and 10 mg, and thiopentone 10 and 20 mg. The basic anaesthesia used was halothane (0.7 vol.%) in N2O/O2 (ratio about 3:1), because renal function, renal autoregulation and responsiveness to renally effective drugs remain nearly unaltered by this anaesthetic procedure. The experimental set-up allowed separate evaluation of effects caused by basic anaesthesia, by intravenous anaesthetic under examination or by the combination of both. All physiological parameters, such as blood gas parameters, plasma electrolytes and intravasal volume were kept in normal range throughout the experiments. Under all anaesthetics studied, RBF reflects the situation of general metabolism especially of cardiac output, as long as sympathetic innervation of the kidneys remains unaltered. Especially the relationship between RBF and CI corresponds with regulative effects in situations without anaesthesia. Within the blood pressure range of autoregulation RBF is greater under ketamine than normal and smaller under fentanyl and etomidate, whereas all other anaesthetics applied show no effect on RBF. Functional "denervation" of the kidney by means of epidural anaesthesia is capable of terminating those effects caused centrally by opioids and transmitted by sympathetic nerves. Diuresis is increased by thiopentone and by ketamine, whereas fentanyl reduces it. The activity of the plasma renin level does not correspond with the degree of renal vascular resistance. The effect of each anaesthetic drug on RBF has principally to be taken as regulative adaptation to altered circulatory conditions. Increasing plasma renin levels are mainly a compensatory reaction following a decline in arterial blood pressure due to anaesthesia induced sympathicolysis. With regard to renal function, the additional use of epidural anaesthesia (functional "denervation" of the kidney) can be recommended especially for highly invasive surgical procedures to antagonize reduction of RBF, which is often induced sympathetically by pain or by commonly used anaesthetic drugs.

Anesthesia, Epidural↗

Computation of the initial distribution of a drug by repetitive convolution with a circulatory transport function.

Hereby we present a widely applicable computational method for the description of recirculation and distribution phenomena occurring immediately after intravenous injection of a substance. The intravascular concentration-time course, r, is described as r = c0 + g * r, where the asterisk denotes the convolution operation, c0 is the concentration-time course during the first passage of the substance at an arterial measuring site and g is the transport function of the body. If the body transport function is known, then the arterial concentration-time course of a substance can be predicted for different amounts, injection times and elimination rates. The site of interest can be chosen arbitrarily, i.e. the concentration-time course in the arterial circulation supplying any organ can be described. This might be of special interest for the optimal design of intravenous injections of contrast media, where initial concentrations at the region of interest determine the success of the diagnostic procedure.

Animals↗

Mechanical left ventricular unloading during high risk coronary angioplasty: first use of a new percutaneous transvalvular left ventricular assist device.

A new catheter mounted, transvalvular left ventricular assist device has been designed for percutaneous transfemoral access. The device, the Hemopump [14 French (Fr.) outer diameter], is based on a mixed flow rotary pump and is capable of flow rates of 1.5-2.2 l/min. The pump is inserted using a specialized 16 Fr. femoral introducer sheath. The first application of the percutaneous Hemopump in man was performed in two patients with hemodynamic compromise during high risk coronary angioplasty. In these patients, Hemopump support resulted in hemodynamic stabilization (increase in aortic pressure from 60/42 to 87/61 and from 80/60 to 100/70 mm Hg, respectively) and marked left ventricular unloading (decrease in pulmonary capillary wedge pressure from 25 to 10 and from 14 to 10 mm Hg) during balloon inflation. In both patients, percutaneous transluminal coronary angioplasty (PTCA) could be accomplished successfully. Using the system for periods of about 2 hr in each patient, we observed no vascular, hemorrhagic, or embolic complications. In both patients, only a minor increase in both plasma free hemoglobin and lactate dehydrogenase levels was noted. Our preliminary experiences suggest that the percutaneous Hemopump is safe and effective and may be a powerful alternative to other devices used for supported angioplasty.

Aged↗

Dopamine-dependent diastolic dysfunction in moderate hypothermia.

We designed an experimental animal study to study the effects of dopamine (DA) on diastolic function in hypothermia. DA was applied at five incremental infusion rates in 6 sheep during normothermia and moderate hypothermia (29 degrees C). Left ventricular end-diastolic pressure (LVEDP) was increased during hypothermia as compared with normothermia at all doses of DA. Contraction and relaxation velocity were changed only slightly during hypothermia; during normothermia, both velocities were markedly increased. The pronounced hemodynamic effect observed during hypothermia was further intensified by occurrence of aftercontractions, which disappeared at very high DA doses. These paradoxic results were considered the result of hypothermia-induced reduction in active transport mechanisms responsible for regulation of the cytoplasmic CA2+ concentration. The generally reduced inotropic effect of DA, the risk of paradoxic reactions, and the occurrence of aftercontractions must be taken into account when emergency drugs are administered clinically during hypothermia.

Animals↗

Efficiency of a new radiant heater for postoperative rewarming.

Effective rewarming devices have only become available recently. This investigation compares the efficiency of an new overhead radiant heater (ARAGONA Thermal Ceilings TM, CTCX, 1000 W) with that of an electric blanket (50 W) or a standard hospital blanket. 35 patients undergoing postoperative assisted ventilation and continued sedation were randomly assigned to one of the treatments. Shivering, oxygen uptake, heart rate and invasive blood pressure were measured and the increase in total body heat minus body heat production was calculated as heat balance. Results are given as medians (range). Subcutaneous temperatures were taken to calculate the mean skin temperature. The evaluation was undertaken for an oesophageal temperature interval of 35 degrees to 37 degrees C. All groups exhibited a similar mean oxygen uptake i.e. thermogenesis (3.5 (2.7-4.0) ml.kg-1.min-1, 3.3 (2.7-4.9) ml.kg-1.min-1;3.2 (2.4-5.1) ml.kg-1. min-1) which correspond to a resting energy expenditure. The time of rewarming of the radiant heat treated group (n = 12) (100 (76-143) min) for this interval was significantly reduced in comparison to both other groups (183 (116-320) min; 231 (115-340) min). A slightly positive heat balance was only achieved in the group treated by radiant heat, indicating that all metabolic heat was conserved or heat losses were compensated by transfer of external heat. Shivering was significantly reduced in the radiant heater group whereas the rate pressure product was insignificantly higher. We did not find any significant effect for the electric heating blanket in comparison to the control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗