A novel, non-invasive diagnostic clinical procedure for the determination of an oxygenation status of chronic lower leg ulcers using peri-ulceral transcutaneous oxygen partial pressure measurements: results of its application in chronic venous insufficiency (CVI).

The basis for the new procedure is the simultaneous transcutaneous measurement of the peri-ulceral oxygen partial pressure (tcPO(2)), using a minimum of 4 electrodes which are placed as close to the wound margin as possible, additionally, as a challenge the patient inhales pure oxygen for approximately 15 minutes. In order to evaluate the measurement data and to characterise the wounds, two new oxygen parameters were defined: (1) the oxygen characteristic (K-PO(2)), and (2) the oxygen inhomogeneity (I-PO(2)) of a chronic wound. The first of these is the arithmetic mean of the two lowest tcPO(2) measurement values, and the second is the variation coefficient of the four measurement values.

Complete healing of chronic wounds of a lower leg with haemoglobin spray and regeneration of an accompanying severe dermatoliposclerosis with intermittent normobaric oxygen inhalation (INBOI): a case report.

A new healing procedure has been developed on the basis of the successful treatment of therapy-resistant hypoxic (and practically anoxic) leg ulcerations located within a heavy dermatoliposclerosis. The procedure involves an initial intra-ulceral application of haemoglobin followed by the intermittent administration of normobaric oxygen via inhalation. Haemoglobin is capable of externally supplying the granulating wound bed with oxygen at low partial pressure in a physiological manner, like a micro lung, so that oxidative stress can be avoided.

[Haemoglobin hyperpolymers, a new type of artificial oxygen carrier -- the concept and current state of development].

In the clinical setting, artificial oxygen carriers are needed when a patient has a tissue oxygen deficiency which he/she can not automatically compensate. There are two quite different situations where this might occur: (1) Heavy blood loss (e. g.

[An extended evaluation of a neuroleptanesthesia for the guinea pig with analysis of mixed expiratory gases during spontaneous breathing. Effects of fasting on the cardiorespiratory system and metabolism].

The artificially ventilated guinea pig was frequently used for neurophysiological and respiratory studies. This species is also preferable for an evaluation of hemoglobin based artificial oxygen carriers, because its oxygen hemoglobin binding is very similar to that of man. But the narcosis of this animal-species is very difficult, because of cardiorespiratory depression induced by conventional procedures.

[Development of a flexible cardiorespiratory monitor based on induction plethysmography].

Induction plethysmography (IP) utilizes changes in the inductance of sinusoidal wires embedded in elastic bands placed around the chest and abdomen to detect volume changes in the two compartments. These changes can be attributed to respiration or heart beat. To date, most applications have been tailored to an investigation of respiration.

New artificial oxygen carriers made of pegulated polymerised pyridoxylated porcine haemoglobin (P(4)Hb).

Oxygen-carrying plasma expanders are designed for use as iso-oncotic 'blood substitutes' to combat oxygen deficiencies caused by blood loss. In contrast, a hypo-oncotic artificial oxygen carrier can be added to existing blood - as a 'blood additive'. It has potential therapeutic use for deficiencies of oxygen which are not entailed by blood (volume) lack, and can therefore not be treated by a 'blood substitute', e.

[A miniaturized, highly sensitive polarimeter as detector in an implantable glucose probe. II. Opto-electronic amplification and processing of measuring signals].

There is a clinical requirement for an implantable telemetric probe for monitoring glucose levels in humans. This probe can measure the glucose content of the intercellular tissue fluid, which reflects glucose levels in the blood. The lifespan of such an implantable probe should be maximal, so that presumably only physical measuring detectors, but not aging-sensitive bio-sensors can be considered.

[Miniaturization capable, very sensitive polarimeter as detector of an implantable glucose probe. I. Optical amplification of the measuring value].

From a clinical point of view, an implantable telemetric probe for monitoring the blood glucose profile is highly desirable. It should be capable of monitoring the blood glucose level continuously or at regular brief intervals, if necessary requirement-controlled. Apart from blood, measurement can also be made in intercellular tissue fluid, for example, in subcutaneous connective and fatty tissue, because this fluid accurately reflects blood glucose levels after only a brief, but negligible, time lag.

A model of stepwise isovolaemic blood exchange in anaesthetised, spontaneously breathing rats to evaluate the oxygen transport efficiency of artificial oxygen carriers.

Our research pursues the production of hypo-oncotic artificial oxygen carriers, based on artificial covalently cross-linked hyperpolymeric mammalian haemoglobins. To evaluate their in vivo efficiency in oxygen delivery to the tissue we developed a small animal model of stepwise isovolaemic blood exchange in anaesthetised, spontaneously breathing rats. With the aid of a two-way respiratory micro valve for small animals the overall oxygen uptake by the tissue of the animal can be determined.

A new measuring device for non-invasive determination of oxygen partial pressure and oxygen conductance of the skin and other tissues.

About fifty percent of the oxygen consumption of the skin is supplied by diffusion through the surface. This portion of the skin oxygen supply becomes of high importance in case of arterial occlusion. The oxygen permeation coefficient (P) of the upper layers and the oxygen pressure field within the skin determine the diffusive oxygen uptake from the outside.

A model for evaluation of artificial oxygen carriers regarding circulation, respiration and metabolism in anesthetized spontaneously breathing guinea pigs.

The evaluation of artificial oxygen carriers requires experiments with suitable animals. Many investigators do this with the classical laboratory animal, the rat, but it has a quite different oxygen pressure of half saturation (p50 = 36 mmHg) from that of humans (26 mmHg). It was demonstrated that induced changes of the p50 value in animals provokes substantial changes in important cardiovascular parameters.

[A new microprocedure for continuous and non-consuming determination of cellular oxygen uptake based on fluorescence quenching].

The oxygen uptake in a cell suspension can be measured by various methods using manometric, paramagnetic or photometric techniques, oximetry, mass spectrometry or radiospectrometry. Easy-to-apply Clark-type electrochemical (polarographic) sensors are by far the most commonly used devices in medical applications. One of their drawbacks is the fact that they consume oxygen and may cause systematic errors when measuring oxygen uptake.

Molar masses and structure in solution of haemoglobin hyperpolymers--a common calibration of size exclusion chromatography of these artificial oxygen carriers.

We are developing artificial oxygen carriers for medical use, based on synthetic polymers--so-called hyperpolymers--obtained by cross-linking mammalian haemoglobins. One requirement with respect to the polymers is that they should not increase the oncotic pressure of blood remarkably--this can be realized by high molecular weights of the polymers with a narrow distribution. They may act as a oxygen transporting blood additive, and--in combination with a plasma expander--as a blood substitute.

[A simple method for improvement of the measurement of respiratory impedance in humans by increasing oropharyngeal impedance using cheek and mouth floor clamps].

It is known, that the upper airway (oropharyngeal) impedance (Z(op)) influences the measured input impedance of the respiratory system (Zrs). This investigation deals with simple methods reducing the artefact caused by Z(op). The following methods have been examined: (1) Supporting the cheeks with fingers, (2) supporting the cheeks and the floor of the mouth with fingers and (3) using a new mechanical clamp for the cheeks and the floor of the mouth.

[Perspectives of a respiratory function analysis].

The necessity to develop procedures to assess respiratory functions which are independent of collaboration, non-invasive, specific, differentiating and sensitive, is stressed. New measuring methods, like main stream detection for oxygen and carbon dioxide as well as continuous assessment of pulmonary impedance are permissive for this purpose. In addition new characteristic quantities are defined.

[An innovative procedure of oxygen detection in medicine, biology, environmental research and biotechnology based on luminescence quenching].

For most (aerobic) animal organisms, oxygen is a mandatory and global substrate. The accurate measurement of oxygen is therefore of importance in the fields of medicine, biology, environmental research and biotechnology. The fact that oxygen is not readily soluble in aqueous media makes its detection more difficult.

[Experiments aimed at developing an implantable and continuously functioning glucose sensors based on polarimetry].

In vitro and in vivo experiments devised with the aim of developing a permanently implantable glucose sensor based on polarimetry are described. It was found that in ultrafiltrated human blood plasma the overall optical rotation was 94% specific for glucose, and that polarisation photometry yielded a sufficiently sensitive signal for in vivo glucose detection. The three types of capillary membrane intended for implantation that we tested, revealed an in vitro response time to glucose concentration of 10 minutes; when implanted, they maintain this over a period of weeks, during which time the same glucose concentrations can be measured daily in ultrafiltrated capillary fluid as in the blood of the animals (guinea pigs).

[A respiratory microvalve for spontaneously breathing anesthetized small animals].

For the accurate functional analysis of the gas exchange in the lungs or evaluation of artificial oxygen carriers in spontaneously breathing anaesthetized small animals, we developed a new respiratory micro-valve. The body of the valve is made of aluminium, and the flaps are made of silicone rubber. The maximum flow rate in a rat measured with a pneumotachograph and the micro-valve was an average of 19.

Divinyl sulfone cross-linked hyperpolymeric human haemoglobin as an artificial oxygen carrier in anaesthetized spontaneously breathing rats.

The production of hyperpolymer haemoglobins, exhibiting sufficiently low colloid osmotic pressure and sufficiently low viscosity is possible, even in concentrations, and therewith oxygen transport capacity, high enough to supply an organism adequately with oxygen. Such hyperpolymers, when infused, are tolerated by anaesthetized rats in acute blood exchange experiments. Ex vivo determinations of plasma colloid osmotic pressure and both, plasma and whole blood kinematic viscosity during blood exchange showed, that corresponding properties found in vivo were refound within the animal.

Influence of the polymerization step alone on oxygen affinity and cooperativity during production of hyperpolymers from native hemoglobins with crosslinkers.

The aim of this study was to find out how the polymerization per se changes oxygen affinity (P50) and cooperativity (n50) of various soluble huge hyperpolymers prepared from native hemoglobins by crosslinking. Increase of cooperativity would be expected considering natural hemoglobin networks. Those hyperpolymers with molecular weights of some 10(6) g/mol are candidates for artificial oxygen-carrying blood additives rather than volume substitutes.

The proton Bohr factor of native and crosslinker treated hemoglobins--its possible significance for the efficacy of hemoglobin based artificial oxygen carriers.

Especially the (alkaline) proton Bohr effect seems to provide an important self regulating mechanism of the organism to deliver specifically oxygen into tissues suffering from O2 deficit. In this way these tissues switch from aerobic to anaerobic metabolism, get lactacid, thereby shifting oxygen hemoglobin binding curve to the right and thus facilitating the oxygen release. The higher the absolute value of the proton Bohr factor (: delta logP50/ delta pH) is the better this mechanism works.

Measurement of phase I volume breath by breath in spontaneously breathing guinea pigs.

A new method to determine phase I volume in tracheotomized spontaneously breathing guinea pigs is presented. Measurements were performed in three animals weighing 567-896 g. In simultaneous tracings of tidal volume (VT) and expiratory profiles of endogenous gases (PO2 or PCO2), the phase I volume of each breath was determined graphically as the volume expired up to the end of phase I of the expirogram.