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D K Harrison

Publications and source records attributed to D K Harrison.

At least 37 records · Page 2Linked to original sources

Transcutaneous hydrogen clearance--a new non-invasive technique for assessing blood flow in human skin.

A new technique for the non-invasive assessment of skin blood flow is described using a modified, commercially available transcutaneous oxygen electrode. Initially, experiments were carried out on normal volunteers at skin temperatures of 40 degrees C and 44 degrees C. Transcutaneous H2 (tcpH2) clearances were measured after the subject had breathed a mixture of 2% H2 in air until a saturation value in the skin had been reached. tcpH2 clearance results were compared with laser Doppler flux values measured simultaneously on adjacent sites and at the same temperatures under control and reactive hyperaemic conditions. Good reproducibility for the tcpH2 technique and significant correlation (p < 0.002) between it and laser Doppler flux values at the same temperatures was demonstrated. In further experiments, (I125) 4-iodoantipyrine clearances (IAP) were carried out immediately prior to and at the same sites as tcpH2 clearances in critically ischaemic lower limbs. The correlation between the methods and the differences between tcpH2 values observed in normal and critically ischaemic skin were highly significant (p < 0.002).

Adult↗

Comparison of macro- and micro-lightguide spectrophotometric measurements of microvascular haemoglobin oxygenation in the tuberculin reaction in normal human skin.

The changes in haemoglobin oxygenation (SO2) occurring in the tuberculin reaction in human skin were measured using macro- and micro-lightguide spectrophotometry and the results compared. A significant difference was found between the measurements from the respective instruments, demonstrating that the micro-lightguide technique measures only in the most superficial capillaries. Laser Doppler flux (LDF) and transcutaneous oxygen (tcpO2) measurements were also obtained concurrently. At the height of the reaction, heating did not significantly change SO2 or LDF, showing that the vessels in the skin were maximally vasodilated. Although SO2 was increased in the reaction, tcpO2 decreased. This suggests that the infiltrating cells may present a diffusion barrier to oxygen between the capillaries and the tissue cells. This study has shown that micro-lightguide spectrophotometry gives a local picture of intracapillary oxygen supply, which is useful in elucidating the pathophysiological changes occurring during chronic inflammation.

Adolescent↗

Effect of hyperoxia at 1 and 2 ATA on hypoxia and hypercapnia in human skin during experimental inflammation.

Transcutaneous PO2 and PCO2 measurements and estimates of skin respiration were monitored at different levels of inspired PO2 in 20 healthy adults during the first 4 days of the tuberculin reaction, a convenient model of acute inflammation. Hyperoxia at 1 and 2 ATA significantly increased transcutaneous PO2 levels in undisturbed and in inflamed skin but did not fully correct the relative hypoxia at the site of inflammation. Hypercapnia was reduced with O2 breathing at 2 ATA. The apparent rate of O2 consumption at the reaction site was raised during hyperoxia, most prominently at 2 ATA. The most intense reactions showed a central relative slowing of laser-Doppler blood flow indicative of microcirculatory impairment. The extent of the relative hypoxia and hypercapnia was greatest in these strongest reactions. The density of lymphocytes and monocytes in biopsies of 48-h reactions was loosely related to the corresponding transcutaneous PO2 measurements. The present study provides evidence that diffusion barriers, in addition to increased local respiration, can contribute to the apparent hypoxia and hypercapnia of this inflammatory model.

Adult↗

Dynamic thermographic imaging for estimation of regional perfusion in the tuberculin reaction in healthy adults.

A sensitive method for measurement of the volume of blood flow through the skin, based on the kinetics of reheating after localised cooling, is described in this paper. This method has been used to study the tuberculin reaction as a model of cutaneous delayed-type hypersensitivity (DHS) in man. Over the positive reaction there is accelerated reheating similar in kinetics and extent to that seen after maximal hyperaemia induced by intradermal injection of histamine or prostaglandin E2. The earlier phase of reheating (10-100 s) is more dependent on blood flow, whereas the later phase (100-300 s) is apparently more dependent on non-perfusion heat exchange mechanisms, including conduction. The reheat kinetic method is largely dependent on blood flow in the deep dermal vessels (diameter > 50 microns), whereas the alternative approach of measurement of the velocity of flow of erythrocytes in the microcirculation by laser Doppler (LD) flowmetry gives results biased towards the most superficial dermal circulation. Previous studies with LD flowmetry have shown that the blood velocity is greatest at the centre of weak and strong reactions, while in the most intense reactions it is raised at the centre but maximal at the periphery (central relative slowing, CRS) raising the possibility of central ischaemia. The reheat kinetics approach has now indicated that the deep dermal circulation is not impaired in CRS reactions. It is concluded that there must be partial obstruction of the parts of the microcirculation communicating between the deep and superficial dermal plexuses, presumably from the accumulation of exudate oedema in the most intense tuberculin reactions.

Adult↗

A preliminary assessment of laser Doppler perfusion imaging in human skin using the tuberculin reaction as a model.

Laser Doppler imaging is a new development in the field of laser Doppler flowmetry. We were recently loaned the Lisca laser Doppler perfusion imager (LDI) manufactured by Lisca Development, Linkoping, Sweden for assessment against other methods for assessment of skin perfusion. In order to evaluate the device, it was applied to imaging flux changes induced in human skin during the tuberculin reaction. Flux values were compared directly with those from conventional lightguide laser Doppler flowmetry, and parameters measured using two other methods for assessment of tissue perfusion, dynamic thermographic imaging and tissue spectrophotometry. The results showed very good correlations between the various methods. In addition, the LDI showed that very large differences in flux values (up to 5 V) could be found within distances of only 2 mm during the tuberculin reaction and that focal centres of low flux values surrounded by higher values ('craters') could be found not only at the centre, but elsewhere in the lesion. The LDI enables rapid non-invasive detailed analysis of blood flow patterns in skin and correlates well with other methods for measuring skin perfusion. Its use to examine heterogeneity of microvascular blood flow patterns may lead to further understanding of the local mechanisms for regulation of oxygen supply to tissue.

Female↗

Spectrophotometric measurements of haemoglobin saturation and concentration in skin during the tuberculin reaction in normal human subjects.

A non-invasive technique employing light-guide spectrophotometry is described for the measurement of haemoglobin concentration and oxygenation in human skin. Measurements were carried out in the visible wavelength range (500-620 nm) and a series of experiments were carried out in vitro and in vivo in order to calibrate the system. Indices were derived for the measurement of relative haemoglobin concentration and absolute oxygen saturation. The technique was applied to measure the changes in these parameters occurring during the course of the tuberculin reaction in human skin. The results are compared with those from laser Doppler flowmetry and transcutaneous oxygen measurements which were carried out concurrently. Divergence between the intracapillary and tissue oxygenation during the course of the reaction provides evidence for the existence of increased diffusion resistance for oxygen; a model is proposed. The study demonstrates the potential clinical usefulness of light-guide spectrophotometry for the non-invasive investigation of tissue oxygen supply.

Adult↗

Regulation of capillary blood flow and oxygen supply in skeletal muscle in dogs during hypoxaemia.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissue PO2 in vivo. Evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow and its distribution. 2. Capillary blood flow and tissue PO2 frequency distribution histograms were measured in the m. sartorius of anaesthetized, relaxed mongrel dogs under conditions of normoxic (Fi, O2 = 0.3) and hypoxic (Fi, O2 = 0.15 and 0.1) artificial ventilation. 3. Stepwise hypoxaemia (hypoxic hypoxia) induced an increasing discrepancy between capillary blood flow and arterial blood flow. The former decreased by 6% whereas the latter increased by 86%. 4. PO2 histograms provided no evidence of cellular anoxia even at Fi,O2 = 0.1. Capillary blood flow histograms suggested a redistribution of the local pattern of flow. 5. A 34.7% reduction of O2 consumption was observed as the result of severe hypoxaemia. 6. The concept of heterogeneity of capillary blood flow as a functional O2 reserve is presented, together with evidence for oxygen-dependent regulation of capillary blood flow and oxygen consumption.

Animals↗

Local oxygen supply and blood flow regulation in contracting muscle in dogs and rabbits.

1. Multiwire surface electrodes were used to measure local hydrogen clearance curves and tissues PO2 in the sartorius muscle in dogs under resting conditions and during stimulation of the muscle at 1, 2, 4, 8 and 20 Hz via the femoral nerve. Tissue oxygen supply was assessed by means of PO2 histograms; evaluation of the initial slopes of the hydrogen clearance curves enabled the measurement of capillary blood flow. 2. In a further model, the analysis of hydrogen clearance curves measured in the femoral vein using intravascular needle electrodes in rabbits enabled the distribution of blood flow to be evaluated both under resting conditions and during direct 2 Hz stimulation of the vastus medialis muscle. 3. Increased oxygen consumption, induced by stimulation, caused increases in capillary flow which were not necessarily accompanied by augmentation of femoral artery flow. 4. PO2 histograms provided no evidence of cellular anoxia even at the maximum level of oxygen consumption. 5. A two-compartment distribution of flow was measured under resting conditions, whereas only one compartment could be resolved during 2 Hz stimulation of the vastus medialis muscle in the rabbit experiments. A clear redistribution of flow was observed in the absence of any increase in total flow. 6. A model for oxygen-dependent regulation of capillary blood flow involving high-flow and normal-flow compartments is proposed.

Anesthesia, Intravenous↗

Effect of hyperoxemia and ritanserin on skeletal muscle microflow.

Serotonin2 (5-HT2) receptor antagonists (ketanserin, ritanserin) can normalize a hyperoxemia-induced disturbance in skeletal muscle oxygenation, presumably by local microflow changes. The purpose of this study was to develop equipment for local hydrogen clearance measurements with a modified eight-channel platinum electrode to assess changes in local skeletal muscle capillary blood flow induced by hyperoxemia and ritanserin (0.035 mg/kg) during hyperoxemia. Laser-Doppler flowmetry was used for regional microflow measurements. Two groups of six anesthetized and artificially ventilated rabbits were studied: group I with normoxemia and hyperoxemia [arterial PO2 (PaO2) 48 kPa; 360 Torr] and group II before and after ritanserin with hyperoxemia (PaO2 46 kPa; 345 Torr). In group I, hyperoxemia induced a mean local hydrogen clearance decrease of 22% while laser-Doppler flowmetry signal decreased 31%. In group II, ritanserin induced a 125% mean local hydrogen clearance increase compared with hyperoxemia (or 37% compared with group I normoxemia); laser-Doppler flowmetry signal increased 30%. The sum distribution of local hydrogen clearances shifted to the left during hyperoxemia and to the right after ritanserin. The conclusion from this study is that local and regional microflow changes can explain the effects of hyperoxemia and ritanserin on skeletal muscle oxygenation.

Animals↗

A multiwire hydrogen electrode for in vivo use.

A multiwire surface electrode is described for measuring the partial pressure of hydrogen gas within extremely small volumes. The purpose was to record hydrogen clearance curves in vivo in order to analyse capillary blood flow. A method for improving the sensitivity and stability of the Clark-type polarographic sensor is presented. The in vitro and in vivo properties were investigated and are critically compared with the characteristics predicted from various models for the polarographic measurements of gases. The high stability and low drift of the electrode together with its small catchment volume (a hemisphere of radius 32 microns) meant that it could be reliably used for accurate, reproducible local measurements of hydrogen clearance curves in vivo. The experiments also demonstrated that the electrode could be used most successfully for the measurement of capillary blood flow even in the heart and contracting skeletal muscle.

Animals↗

Local hydrogen clearance as a method for the measurement of capillary blood flow.

A hydrogen clearance technique for the measurement of capillary blood flow in skeletal muscle (both resting and working) and the beating heart in experimental animals is described. Various methods for introducing the hydrogen into the region of measurement are compared, together with the appropriate methods for evaluating the resultant curves. All methods yielded results which were proportional to each other signifying that this is a reliable method for measuring changes in capillary blood flow. Reproducible results were obtained, and physiological changes in flow could be easily detected. An approach towards obtaining absolute flow values is proposed by simultaneous measurement of the arterial input function together with the independent use of other indicators.

Animals↗

Cerebrocortical microcirculation in different stages of hypoxic hypoxia.

This study investigated the relation between local cerebrocortical oxygen tension (PO2) and cerebrocortical microflow (CMF) during normoxia (FiO2 = 0.3) and hypoxic hypoxemia (FiO2 = 0.16 and 0.1). Measurements were performed on mechanically ventilated rats and rabbits anesthetized with 0.8% Ethrane and maintained within normocapnic limits. Polarographic techniques based on the use of multiwire surface electrodes were applied for measurements of local PO2 and CMF. In both species the mean tissue PO2 values were similar under normoxia (26.0 and 31.5 mm Hg for rats and rabbits, respectively). CMF histograms showed pronounced heterogeneity. The highest CMF values exceeded the lowest ones by a factor of 36 in the rat and by a factor of 26 in the rabbit. Mean CMF values were 6.67 +/- 0.72 and 4.09 +/- 0.14 relative units (for definition see text) in rats and rabbits, respectively. During hypoxemia, if the mean tissue PO2 was greater than 5 mm Hg, mean CMF did not change but a change in the pattern of microflow distribution was observed with increases in some CMF values (up to 670% of control) and decreases in others (down to 12% of control). When mean tissue PO2 values of less than 5 mm Hg were observed during hypoxemia, mean CMF increased in both species by approximately 50% on average. The increase in CMF could be seen in each individual CMF recording. We conclude that in the brain cortex local regulatory mechanisms are responsible for the change in the pattern of distribution of microcirculation during moderate tissue hypoxia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

pH changes in the dermis during the course of the tuberculin skin test.

The response of six healthy young adults to tuberculin skin testing was studied. Five subjects developed a typical delayed-type hypersensitivity reaction to PPD with a local rise in skin temperature, and the sixth showed a less intense response; a considerable increase in blood flow velocity was seen in all reactions. All subjects showed a fall in pH in the dermis during the course of the reaction: in four subjects the pH minimum occurred at the time when the changes of erythema and induration were most prominent, in one subject the pH fall preceded the maximal clinical changes, and in the remaining subject a substantial fall in pH occurred with only transient erythema. It was concluded that the local tissue acidosis had resulted from the greatly increased metabolic demand of the lymphocytes and monocytes attracted into the dermis as part of the type IV delayed-type hypersensitivity reaction, and that the concurrent reactive hyperaemia was insufficient to clear the acidic metabolic products of the greatly increased cell population.

Adult↗