Alpha-GlcNAc thioconjugates.
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Acetylglucosamine↗
Biomedical subjects
D S Myers
Publications and source records attributed to D S Myers.
Reflex responses from the main pulmonary artery and bifurcation in anaesthetised dogs.
This study was undertaken to determine the reflex cardiovascular and respiratory responses to discrete stimulation of pulmonary arterial baroreceptors using a preparation in which secondary modulation of responses from other reflexes was prevented. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The main pulmonary arterial trunk, bifurcation and extrapulmonary arteries as far as the first lobar arteries on each side were vascularly isolated and perfused through the left pulmonary artery and drained via the right artery through a Starling resistance which controlled pulmonary arterial pressure. Pressures distending systemic baroreceptors and reflexogenic regions in the heart were controlled. Reflex vascular responses were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic systemic circulation, both of which were perfused at constant flows. Respiratory responses were assessed from recordings of efferent phrenic nerve activity. Increases in pulmonary arterial pressure consistently evoked increases in both perfusion pressures and in phrenic nerve activity. Both vascular and respiratory responses were obtained when pulmonary arterial pressure was increased to above about 30 mmHg. Responses increased at higher levels of pulmonary arterial pressures. In 13 dogs increases in pulmonary arterial pressure to 45 mmHg increased systemic perfusion pressure by 24 +/- 7 mmHg (mean +/- S.E.M.) from 162 +/- 11 mmHg. Setting carotid sinus pressure at different levels did not influence the vascular response to changes in pulmonary arterial pressure. The presence of a negative intrathoracic pressure of -20 mmHg resulted in larger vascular responses being obtained at lower levels of pulmonary arterial pressure. This indicates that the reflex may be more effective in the intact closed-chest animal. These results demonstrate that stimulation of pulmonary arterial baroreceptors evokes a pressor reflex and augments respiratory drive. This reflex is likely to be elicited in circumstances where pulmonary arterial pressure increases and the negative excursions of intrathoracic pressure become greater. They are likely, therefore, to be involved in the cardio-respiratory response to exercise as well as in pathological states such as pulmonary hypertension or restrictive or obstructive lung disease.
Animals↗
Absence of reflex vascular responses from the intrapulmonary circulation in anaesthetised dogs.
The aim of this investigation was to determine whether reflex cardiovascular responses were obtained to localised distension of the intrapulmonary arterial and venous circulations in a preparation in which the stimuli to other major reflexogenic areas were controlled and the lung was shown to possess reflex activity. Dogs were anaesthetised with -chloralose, artificially ventilated, the chests widely opened and a cardiopulmonary bypass established. The intrapulmonary region of the left lung was isolated and perfused through the left pulmonary artery and drained through cannulae in the left pulmonary veins via a Starling resistance. Intrapulmonary arterial and venous pressures were controlled by the rate of inflow of blood and the pressure applied to the Starling resistance. Pressures to the carotid, aortic and coronary baroreceptors and heart chambers were controlled. Responses of vascular resistance were assessed from changes in perfusion pressures to a vascularly isolated hind limb and to the remainder of the subdiaphragmatic circulation (flows constant). The reactivity of the preparation was demonstrated by observing decreases in vascular resistance to large step changes in carotid sinus pressure (systemic vascular resistance decreased by -40 +/- 5%), chemical stimulation of lung receptors by injection into the pulmonary circulation of veratridine or capsaicin (resistance decreased by -32 +/- 4%) and, in the four dogs tested, increasing pulmonary stroke volume to 450 ml (resistance decreased by -24 +/- 6%). However, despite this evidence that the lung was innervated, increases in intrapulmonary arterial pressure from 14 +/- 1 to 43 +/- 3 mmHg or in intrapulmonary venous pressure from 5 +/- 2 to 34 +/- 2 mmHg or both did not result in any consistent changes in systemic or limb vascular resistances. In two animals tested, however, there were marked decreases in efferent phrenic nerve activity. These results indicate that increases in pressure confined to the intrapulmonary arterial and venous circulations do not cause consistent reflex vascular responses, even though the preparation was shown to be reflexly active and the lung was shown to be innervated.
Animals↗
Reflex control of splanchnic blood volume in anaesthetized dogs.
1. In chloralose-anaesthetized, artificially ventilated dogs, the splenic pedicle was tied and the carotid sinuses were vascularly isolated and perfused at controlled pressures. In Series 1 experiments, the hepatosplanchnic circulation was perfused through the abdominal aorta with a tie on the aorta separating it from the caudal circulation, which was perfused through the femoral arteries. The two circulations were drained from cannulae in the inferior vena cava and the femoral veins, with a tie on the inferior vena cava separating the two. In Series 2, the splanchnic circulation drained from the portal vein. In both series, inflows and outflows were measured and integrated to derive volume changes. Capacitance responses were assessed during constant flow, and capacitance plus passive responses were obtained during constant pressure perfusion. 2. In Series 1, an increase in carotid sinus pressure (from 8 to 26 kPa) during constant flow and constant pressure perfusion increased hepatosplanchnic volume by 2.5 and 5.7 ml (kg body weight)-1, respectively. The volume of the subdiaphragmatic circulation did not increase during constant flow, but during constant pressure it increased by 2.0 ml (kg body weight)-1. 3. In Series 2, increasing carotid pressure during constant flow and constant pressure increased the volume of the splanchnic circulation by 0.5 and 4.2 ml (kg body weight)-1, respectively. 4. These results confirm that carotid baroreceptor stimulation causes larger volume changes during constant pressure perfusion than during constant flow perfusion. Also, the active capacitance change in the splanchnic circulation is small in relation to the passive response. We propose that in dogs (following splenic ligation), the major active capacitance control is from the liver. However, large passive changes in splanchnic volume occur due to changes in flow.
Anesthesia↗
Blood mobilization from the liver of the anaesthetized dog.
The abdominal circulation contains a high proportion of the total blood volume and this can change either passively in response to changes in vascular distending pressure or actively (termed a capacitance response) to changes in sympathetic nervous activity. The liver is the largest abdominal organ and this study was designed to evaluate its potential contribution to overall vascular capacitance and compliance. In chloralose anaesthetized dogs, the liver was vascularly isolated, perfused through the portal vein and hepatic artery at either constant pressures or constant flows and drained from the hepatic veins at constant pressure. Changes in vascular resistance were assessed from changes in inflow pressures or flows and hepatic blood volume was determined by differences between net inflow and outflow. During constant flow perfusion the change in hepatic volume (capacitance change) in response to supramaximal stimulation of sympathetic nerves at 16 Hz was (mean +/- S.E.M.) -2.40 +/- 0.61 ml (kg body weight)-1. This response was not significantly different during constant pressure perfusion. The changes in portal venous and hepatic arterial pressures during stimulation at constant flow perfusion were +0.67 +/- 0.13 and +4.92 +/- 0.67 kPa, respectively. The compliance of the liver, assessed as the change in volume to a change in hepatic venous pressure, was +5.44 +/- 0.18 ml kg-1 kPa-1. These results indicate that the liver has a major capacitance role, comparable to that of the canine spleen and, in addition, is highly compliant. No evidence was found to suggest that a sphincter on the hepatic outflow exists. Assuming similar responses occur in humans, who do not possess a large contractile spleen, the liver would be the most important controllable blood reservoir in the body.
Anesthesia↗
Reflex vascular responses in the anesthetized dog to large rapid changes in carotid sinus pressure.
This study examined reflex vascular responses to large rapid increases and decreases in carotid sinus pressure to determine whether delayed or inappropriate vascular responses might be obtained that, if they occurred in people, could lead to hypotension during exposure to rapidly alternating gravitational forces. In chloralose-anesthetized open-chest dogs, a perfusion circuit controlled carotid sinus and thoracic aortic pressures and blood flows to both the vascularly isolated abdominal circulation and a hindlimb (perfusion pressure changes denoted resistance). When carotid pressure was increased and decreased over the range of 60-180 mmHg, the resulting reflex vasodilatation occurred significantly more rapidly than the vasoconstriction (P < 0.001). In the abdominal vascular bed, time constants for vasodilatation and vasoconstriction were 4.2 +/- 0.5 and 7.5 +/- 1.0 s, respectively. Decreases in carotid pressure in pulses of 10-s duration or less failed to elicit maximal vasoconstriction, whereas increases in carotid pressure lasting as little as 5 s did elicit maximal vasodilatation. "Square-wave" alternations in carotid pressure with periods of 10 s or less (5 s high, 5 s low) resulted in attenuation of the vasoconstriction, and at a 4-s period, both vascular beds remained almost maximally vasodilated throughout. The failure of vascular resistance to follow carotid pressure changes was not due to a failure of the response of sympathetic efferent activity, since the time constants for the reduction and increase in discharge were much shorter at 0.56 +/- 0.13 and 0.43 +/- 0.10 s, respectively. These results indicate that rapid changes in carotid pressure could result in inappropriate vasodilatation and hypotension and might, in some circumstances, such as in pilots flying high-performance aircraft, predispose to syncope.
Anesthesia, Intravenous↗
Mechanisms responsible for changes in abdominal vascular volume during sympathetic nerve stimulation in anaesthetized dogs.
This study was designed to determine the extent to which the decrease in volume of blood in the abdominal circulation in response to sympathetic stimulation was due to a passive effect of decreasing flow rather than active constriction of the capacitance vessels. In dogs anaesthetized with alpha-chloralose (100 mg kg-1 i.v.) the abdominal circulation was vascularly isolated and perfused either at constant flow or at constant pressure, and drained at constant pressure from the inferior vena cava. Changes in volume were determined by integration of the differences between inflow and outflow. Supramaximal stimulation of both splanchnic (sympathetic) nerves at 1 Hz decreased abdominal volume during constant pressure perfusion (active and passive components) by 3.04 +/- 0.58 ml kg-1 and at constant flow (active responses only) by 2.30 +/- 0.49 ml kg-1 (means +/- S.E.M.). The responses at 8 Hz were respectively 9.52 +/- 0.91 and 5.09 +/- 0.49 ml kg-1. The proportion of the responses calculated to be passive at 1 and 8 Hz was 23 +/- 6.3 and 45 +/- 5.1%, respectively. These responses were almost identical to those induced by changing inflow by increasing the pump speed. Following ligation of the splenic pedicle, the responses during both constant pressure and constant flow were reduced by similar amounts, indicating that only the active response was affected. After ligation of the splenic pedicle, the proportion of the response calculated to be passive at 1 and 8 Hz increased to 44 +/- 8.0 and 62 +/- 3.7% respectively. These results indicate the importance of passive volume change in affecting abdominal volume, particularly following ligation of the splenic circulation.
Abdomen↗
Reflex vascular responses to alterations in abdominal arterial pressure and flow in anaesthetized dogs.
The existence of abdominal arterial baroreceptors has long been controversial. Previously difficulties have been encountered in localizing a stimulus to abdominal arteries without affecting reflexogenic areas elsewhere. In these experiments, using anaesthetized dogs, the abdomen was vascularly isolated at the level of the diaphragm, perfused through the aorta, and drained from the inferior vena cava to a reservoir. Changes in abdominal arterial pressure were effected by changing the perfusion pump speed. During this procedure the flow back to the animal from the venous outflow reservoir was held constant. Increases and decreases in abdominal arterial pressure resulted, respectively, in decreases and increases in perfusion pressure to a vascularly isolated hind-limb and in some dogs also a forelimb. Responses were significantly larger when carotid sinus pressure was high (120-180 mmHg) than when it was low (60 mmHg). Responses were still obtained after cutting vagus, phrenic and splanchnic nerves, but were abolished by spinal cord lesion at T12. These experiments provide evidence for the existence of abdominal arterial baroreceptors. The afferent pathway for the reflex vasodilatation appears to run in the spinal cord.
Abdomen↗
Reflex vascular responses to abdominal venous distension in the anesthetized dog.
This was undertaken to determine whether distension of the subdiaphragmatic veins results in reflex vasoconstriction and interacts with the carotid baroreflex. In alpha-chloralose-anesthetized open-chest dogs, a perfusion circuit controlled carotid and thoracic aortic pressures, splanchnic and limb blood flows, and cardiopulmonary blood flows. At carotid sinus pressures below approximately 90 mmHg, increases in splanchnic pressure of 7 mmHg or more resulted in increases in vascular resistance in both the splanchnic and limb circulations; there was no response at higher carotid pressures. At high venous pressures, the average maximum gains of the carotid baroreflex for splanchnic and limb resistance responses were increased by 106 and 67%, respectively. The responses were not abolished by cutting the vagal or phrenic nerves but were prevented by cutting the splanchnic nerves and, for the limb, the sciatic and femoral nerves. These results suggest that splanchnic congestion, by causing vasoconstriction and augmentation of the carotid baroreflex, may be important in the maintenance of blood pressure during gravitational stress.
Abdomen↗
The effect of anticoagulant choice on apparent total antioxidant capacity using three different methods.
We assessed total antioxidant capacity using three different methods, in plasma samples treated with either EDTA or heparin as anticoagulant, from 26 healthy subjects. Total antioxidant capacity was determined using an oxygen electrode (as the total peroxyl radical-trapping antioxidant parameter), by enhanced chemiluminescence, and by measurement of the antioxidant-mediated quenching of the absorbance of a radical cation. The choice of anticoagulant had a profound effect on antioxidant capacity with heparinized plasma giving consistently higher values than plasma anticoagulated with EDTA. Using the oxygen electrode the mean value was 786.5 +/- 171.5 mumol/L (heparin) compared to 681.4 +/- 160.4 mumol/L (EDTA, P < 0.01). The chemiluminescence technique gave a mean antioxidant capacity of 915.6 +/- 214.1 mumol/L in heparin samples and 714.4 +/- 195.4 mumol/L in EDTA samples (P < 0.0001). The absorbance quenching technique gave a mean value of 867.0 +/- 199.2 mumol/L (heparin) and 675.5 +/- 245.4 mumol/L (EDTA, P < 0.001). All methods tested showed comparable results for EDTA plasma, but the chemiluminescence technique gave higher apparent antioxidant capacity than either of the two techniques when heparin plasma was used. We suggest that either heparin is interacting to enhance antioxidant protection perhaps through release of superoxide dismutase, or the chelation of metal ions by EDTA is limiting the activity of antioxidant metalloenzymes. Consistency in the choice of anticoagulant is clearly extremely important.
Adult↗
The effect of propofol anaesthesia on free radical-induced lipid peroxidation in rat liver microsomes.
In order to assess the in vivo significance of the free radical scavenging properties of propofol the effect of propofol anaesthesia on the sensitivity of rat liver microsomes to radical-induced lipid peroxidation has been examined. Microsome peroxidation was initiated with a combination of reduced nicotinamide adenine dinucleotide phosphate and ferric ions, and assessed by measuring the changes in oxygen tension in the microsome suspension. In comparison to animals receiving 10% intralipid, saline or midazolam, microsomes prepared from animals anaesthetized with propofol demonstrated a significantly increased resistance to lipid peroxidation. Thus, the median delay in onset of the maximum rate of oxygen consumption in animals receiving a bolus of propofol was 23.1 min (range 14.4-32.3), in comparison to delays in the animals receiving intralipid, saline or midazolam of 1.9 (0.5-4.1), 2.4 (2.0-3.7) and 3.0 (1.8-6.1) min respectively (P < 0.01 in each case, Mann Whitney U-test). More prolonged anaesthesia with either repeated boluses or an infusion of propofol also delayed the onset of lipid peroxidation (45.6 (27.2-60) and 18.3 (9.2-60) min respectively). We conclude that the free radical scavenging properties of propofol are biologically significant at anaesthetic doses.
Anesthesia, Intravenous↗
The antioxidant potential of propofol (2,6-diisopropylphenol).
We have examined in vitro the antioxidant properties of 2,6-diisopropylphenol. In studies using electron spin resonance spectroscopy we have demonstrated that 2,6-diisopropylphenol acts as an antioxidant by reacting with free radicals to form a phenoxyl radical--a property common to all phenol-based free radical scavengers. In additional experiments, the antioxidant properties of the clinical formulation of 2,6-diisopropylphenol (propofol) have been measured using an assay of antioxidant potential. In these experiments, propofol, but not Intralipid, was found to exhibit significant antioxidant activity, such that in the range of propofol concentrations examined (10(-6)-10(-5) mol litre-1), each molecule of 2,6-diisopropylphenol was able to scavenge two radical species. We conclude that the free radical scavenging properties of 2,6-diisopropylphenol resemble those of the endogenous antioxidant alpha-tocopherol (vitamin E).
Antioxidants↗
Direct detection of free radical generation in an in vivo model of acute lung injury.
Electron spin resonance (ESR) spectroscopy has been used to provide direct evidence that free radical production occurs in an in vivo model of acute lung injury. Two experimental groups of rabbits were given the spin trap alpha-phenyl N-tert.-butyl nitrone (PBN), together with endotoxin in the test group, and saline in the control group. Both groups were subsequently briefly ventilated with air containing cigarette smoke. Plasma samples from the endotoxin pretreated group showed a sudden burst of radical formation, detected as PBN spin adduct, which peaked in the first ten minutes after smoke exposure. No signals were detected in the control group. Permeability of the alveolar capillary barrier of the lung, measured by the clearance of 99mTc-DTPA, demonstrated significantly greater damage following smoke in the endotoxin primed animals than in the controls. Temporal studies suggest that this increase in permeability occurred after a burst of radical production. These studies provide supportive evidence for the hypothesis that endotoxin promotes the accumulation of a population of primed white cells within the lung, which when triggered by cigarette smoke, are able to generate a burst of free radicals which produce tissue damage and acute lung injury.
Animals↗
Active and passive tactual recognition of form.
Subjects (N = 30) actively touched forms with the preferred palm or were restricted to passive touch, where forms were either statically or sequentially pressed on the palm. Visual matches to tactual standards were made with unlimited stimulus exposure time. Active touch was superior to both forms of passive touch in recognition accuracy. The provision of sequential presentations and stimulus change failed to aid passive touch.
Adult↗
A plea for consistent lung burden criteria for insoluble alpha emitting isotopes.
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Aerosols↗