J. Höper

Tissue O2 Supply Under Normal and Pathological Conditions

Systematic investigations of a variety of local parameters which form part of the complex functional chain responsible for delivery of oxygen to tissues revealed that most relevant information can be obtained by direct measurements of the oxygen tension field (Po2 histogram) by means of Clark-type and Po2 needle electrodes.

Local Oxygen Supply and Regional Wall Motion of the Dog’s Heart During Critical Stenosis of the Lad

When open heart surgery is performed in order to bypass stenosed coronary arteries by a vein graft, the heart surgeon often discovers hypokinetic zones in the poorly perfused area of the myocardium.

Microcirculation and Po2 in Skeletal Muscle During Respiratory Hypoxia and Stimulation

The regulation of blood flow to skeletal muscle has, for many years, been the subject of much research (Hudlicka, 1973) with the result that nowadays many phenomena can be explained by the presence of local oxygen sensors which serve to regulate the flow in order to maintain an adequate oxygen supply to the tissue (Granger and Shepherd, 1973). For example, the vasodilation which occurs during hypoxia almost certainly takes place as a result of signals from such sensors, and there is strong evidence to suggest that the majority of these sensors may be located in the tissue cells (Kessler et al., 1983).

Effect of amifostine (Ethyol®) on the development of extraembryonic blood vessels in chick embryos

AimSystemic and local side effects can limit radioas well as chemotherapy in patients suffering from neoplastic discaccs One possibility to reduce the therapy-dependent side effects is to attenuate radical induced alterations of normal healthy tissue by application of antioxidants. Preclinical and clinical studies demonstrated the ability of amifostine to protect normal, but not neoplastic, tissues from cytotoxic effects of chemotherapy or irradiation. The purpose of the present study was to establish whether amifostine (Ethyol®) can affect microvessel density in vivo.Material and MethodsFor this study fertilized crossbred ldWhite-Plymouth-Rocks x Sussexrd eggs were used. After 48 hours of incubation 0.05 ml solution containing 25.7 μg (approximately 120 μM) amifostine were injected next to the germ disc. Taking into account the mean surface area of the area vasculosa and the embryo, this corresponds to a dose of 26 μg/cm2. As controls, the area vasculosa of eggs treated with 0.05 ml NaCl 0.9% were used. Twenty-four and 48 hours after injection of amifostine or NaCl photographs and video microscopic pictures from treated areas and controls were taken and evaluated for vascular density. Results of vascular density are given as vascular intersections per mm2 (VIS/mm2).ResultsThere was a significant (p < 0.001) difference in vascular density with a mean microvessel count of 30.40 (± 12.84 SD) VIS/mm2 in the NaCl control and 53.69 (±24.56 SD) VIS/mm2 in the amifostine-treated area vasculosa.ConclusionThe results show that amifostine induced an increase in vascular density in the rapidly proliferating area vasculosa of the early chick embryo.ZusammenfassungZielSystemische und lokale Nebenwirkungen sind hÄufig begrenzende Faktoren einer Strahlenoder Chemotherapie. Eine Möglichkeit, diese therapieinduzierten Nebenwirkungen zu reduzieren und damit das normale Gewebe zu schützen, besteht in der Gabe von Antioxidanzien. PrÄklinische und klinische Studien haben gezeigt, da\ Amifostine normales Gewebe vor den zytotoxischen Effekten sowohl der Strahlenals auch der Chemotherapie schützt. Ziel der vorliegenden In-vivo-Studie war es zu prüfen, ob Amifostine (Ethyol®) einen Einflu\ auf die GefÄ\dichte hat.Material und MethodeDie Untersuchungen wurden an fertilisierten Eiern der Rassenkreuzung ldWhite-PlymouthRocks x Sussexrd durchgeführt. Nach einer Bebrütungsdauer von 48 Stunden wurden 0,05 ml Lösung mit 25,7 μg (ca. 120 μM) Amifostine nahe der Keimscheibe injiziert. Unter Berücksichtigung der FlÄche von Area vasculosa und Embryo entsprach dies einer Dosierung von 26 μg/cm2. Als Kontrolle dienten Anteile der Area vasculosa nach Behandlung mit 0,05 ml NaCl 0,9%. 24 und 48 Stunden nach Injektion von Amifostine oder NaCl wurden die Areale videomikroskopisch aufgenommen. An diesen Bildern wurde histometrisch die GefÄ\dichte bestimmt. Die Ergebnisse werden als GefÄ\schnittpunkte/mm2 (vascular intersections/mm2 = VIS/mm2) dargestellt.ErgebnisseDie GefÄ\dichte betrug in den NaCl-Kontrollen 30,40 (± 12,84 SD) VIS/mm2. Nach Behandlung mit Amifostine wurde eine Zunahme auf 53,69 (± 24,56 SD) VIS/mm2 beobachtet. Der Unterschied zu der Kontrollgruppe war signifikant (p < 0,001).Schlu\folgerungDie Daten zeigen, da\ Amifostine eine Zunahme der GefÄ\dichte in der stark proliferierenden Area vasculosa des Hühnerembryos induziert.

Oxygen Supply of the Myocardium

Hypokinetic zones in the myocardium develop when the oxygen supply of the myocytes is diminished. For quite a long time it was supposed that a local depletion of energy rich phosphates might be the cause of disturbances of wall motion in the critically perfused myocardium.

Spatial Distribution of Oxygen Supply Units in Heart and Skeletal Muscle and their Regulatory Significance

Investigations of local pO2 in skeletal and heart muscle revealed unexpected results. In both organs local pO2 measurements demonstrated that tissue oxygenation is structured in such a way that 10–15 characteristic O2 supply units do exist (see figures 1 and 2). Each individual supply unit shows a rather homogeneous distribution of the spatial pO2 profiles (Kessler et al. 1984). In skeletal muscle the size of the individual unit is approximately 400–600 μm in length with a diameter of approximately 150–200 μm. In such functional structures with relatively homogeneous patterns of capillary blood flow large pO2 gradients between the individual supply units are not induced. This prevents loss of oxygen by diffusion shunt.

Oxygen Supply and Microcirculation of the Beating Dog Heart after Haemodilution with Fluosol DA20

Previous studies on local tissue oxygen supply after haemodilution with the colloidal perfluorocarbon Fluosol DA20% (FDA20%) carried out in the liver (Hoper et al., 1982), pancreas, kidney and skeletal muscle (Kessler et al., 1982), and the heart (Vogel et al., 1983; Kessler et al., 1983) have demonstrated that an improvement in local tissue oxygen supply was observed which was greater than could be explained simply in terms of the increased quantity of oxygen delivered by the fluo-rocarbon. It was evident that changes in flow occured (Hoper et al., 1982), probably at the microcirculation 1evel.

Regulation of reactive hyperaemia in the kidney.

As shown by Sinagowitz et al. (1977) the behaviour of post i schaemic hyperaemia in the kidney is complex, and depends on the duration of the ischaemic period. In order to investigate the relation between the total renal blood flow (RBF), local oxygen supply and oxygen uptake rate under these conditions, experiments were performed in the kidneys of anaesthetized dogs.

Measurement of Local Po2 and Intracapillary Hemoglobin Oxygenation in Lung Tissue of Rabbits

To date investigations of the mechanisms involved in the ventilation and perfusion of the lung have only been carried out by indirect methods. The disadvantage of such methods is that the local distribution of these parameters within the lung, particularly in the alveolar-capillary area, cannot be adequately determined.

Correlation Between Tissue Po2 and Intracapillary Hb Spectra

The development of highly flexible micro light guides by Ji et al. (1979) made possible the construction of a spectrophotometer for measuring intracapillary hemoglobin oxygenation. Due to the flexibility, good contact between the light guides and the tissue is ensured. The photometer has already been used successfully for measurements in the beating heart, the lung and the skeletal muscle.