Fusimotor activity and the tendon jerk in the anaesthetised cat

This is a study of the tendon jerk reflex elicited by a brief stretch applied to the triceps surae muscle group in the chloralose-anaesthetised cat. The size of the recorded reflex depended on stretch parameters (optimum at 300 μm amplitude at a rate of 100 mm/s) and on how the muscle had been conditioned. A reflex elicited after a conditioning contraction at the test length was often twice as large as after a contraction carried out at a length longer than the test length. This difference was attributed to the amount of slack introduced in the intrafusal fibres of muscle spindles by conditioning. The question was posed, did ongoing fusimotor activity exert any influence on the size of the tendon jerk? Depolarization indices (DPI) were calculated from responses of muscle spindles to stretch and correlated with the level of reflex tension. Values of DPI obtained from afferent responses with and without repetitive stimulation of identified fusimotor fibres suggested that with the stretch parameters used here the main influence of fusimotor activity was that it removed any pre-existing slack in muscle spindles and thereby increased reflex tension. In the absence of intrafusal slack, stimulation of static and dynamic fusimotor fibres had little additional influence on the size of the reflex. It is concluded that much of the variability typically seen with tendon jerks is due to muscle history effects. Since in muscles which have not been deliberately conditioned there is commonly some slack present in spindles, activity in fusimotor fibres is likely to reduce slack and therefore increase reflex size.     

Cardioventilatory coupling in the anaesthetised rabbit, rat and guinea-pig

 Cardioventilatory coupling is a temporal coherence of respiratory and cardiac rhythms, seen in humans at rest, and during sleep and anaesthesia. In this study we compared the cardioventilatory coupling of anaesthetised rabbits, rats and guinea-pigs. Breathing two successive anaesthetic concentrations (1 or 2% isoflurane) we compared the effect of anaesthetic depth and species on (1) heart rate, (2) heart rate variability, (3) ventilatory rate (f), (4) ventilatory variability, (5) ratio HR/f, (6) degree of coupling (Shannon entropy of the distribution of intervals between inspiration and the preceding electrocardiographic R wave – the RI interval) and (7) coupling pattern, classified into four sub-patterns (I-IV) based upon inspection of the RI interval time series. Rabbits exhibited significantly less ventilatory variability and coupling than rats or guinea-pigs. The sub-pattern of coupling also differed between the three species. Rabbits showed coupling only when HR and f were close to integer ratios whereas other species coupled at non-integer ratios. Ventilatory variability in the rat and guinea-pig differed according to the pattern of coupling observed. Of the three species studied, the rat and guinea-pig demonstrated coupling most similar to that of anaesthetised human subjects. Anaesthetic concentration did not influence the pattern or degree of coupling. Received: 28 July 1998 / Received after revision: 24 November 1998 / Accepted: 8 January 1999     

Down综合征16三体小鼠胃的神经发育观察

目的　研究Dow n 综合征动物模型16 三体和正常同窝鼠支配胃的神经发育。方法　采用16三体鼠培育,同窝鼠胚胎龄(em bryonic days, ED)13～18 天细胞遗传学分析,蛋白基因产物9.5(proteingene product 9.5, PGP9.5)免疫组化等方法对16 三体小鼠胃的神经发育进行了研究。结果　正常同窝鼠,胎龄13 天(ED13)来源于外胚层神经嵴的神经母细胞迁移并进驻胃壁;ED14 神经元发出突起,形成原始神经网络;ED15 形成简单排列的肌间神经丛,开始出现早期的神经节;ED16 有分布规则的肌间神经丛;ED17 神经母细胞进驻粘膜下层,形成粘膜下神经丛;ED18 完整的胃神经丛形成,即粘膜下浅、深神经丛和肌间神经丛。与正常同窝鼠比较,16 三体鼠胃神经系发育迟缓,ED14 胃壁始有散在分布神经元。此后,胃神经系的发育与分化均较正常延迟,至ED18 仅有肌间神经丛。根据胃神经系的发育程度和PGP9.5 免疫反应强度作半定量分析及秩和检验,16 三体鼠胃神经的发育明显落后于它们正常的同窝鼠,两者比较有显著性差异(P< 0.05)。结论　16 三体小鼠是公认的Dow n 综合征动物模型,它除了有多系统和多器官的畸型外,还发现有小鼠胃神经丛发育迟缓,粘膜下神经丛缺失。     

Gaseous transmitters in human retinogenesis

Endogenous gaseous transmitters (nitric oxide, carbon monoxide, and hydrogen sulphide) form a special neuromodulation system mediating the development and modification of nerve centers. Here, we examined the localization of key gaseous transmitter enzymes: cystathionine β-synthetase (CBS), cystathionine γ-lyase (CSE), heme oxygenase 2 (HO-2), and constitutive NO synthase (nNOS) in the fetal human retina at different stages of development. The number of CBS- and CSE-positive photoreceptors and intermediate retinal neurons was high in trimester I and gradually decreased to the end of trimester III. The number of HO-2-positive cells followed the same trend. The number of nNOS-positive intermediate retinal neurons and neurons within the ganglion cell layer showed the opposite dynamics with the peak in trimester III. The results are interpreted in terms of the role of gaseous transmitters in retinogenesis and cytoprotection.     

Gaseous messengers in oxygen sensing

The carotid body is a sensory organ that detects acute changes in arterial blood oxygen (O₂) levels and reflexly mediates systemic cardiac, vascular, and respiratory responses to hypoxia. This article provides a brief update of the roles of gas messengers as well as redox homeostasis by hypoxia-inducible factors (HIFs) in hypoxic sensing by the carotid body. Carbon monoxide (CO) and nitric oxide (NO), generated by heme oxygenase-2 (HO-2) and neuronal nitric oxide synthase (nNOS), respectively, inhibit carotid body activity. Molecular O₂ is a required substrate for the enzymatic activities of HO-2 and nNOS. Stimulation of carotid body activity by hypoxia may reflect reduced formation of CO and NO. Glomus cells, the site of O₂ sensing in the carotid body, express cystathionine γ-lyase (CSE), an H₂S generating enzyme. Cth ^−/− mice, which lack CSE, exhibit severely impaired hypoxia-induced H₂S generation, sensory excitation, and stimulation of breathing in response to low O₂. Hypoxia-evoked H₂S generation in the carotid body requires the interaction of CSE with HO-2, which generates CO. Carotid bodies from Hif1a ^+/− mice with partial HIF-1α deficiency do not respond to hypoxia, whereas carotid bodies from mice with partial HIF-2α deficiency are hyper-responsive to hypoxia. The opposing roles of HIF-1α and HIF-2α in the carotid body have provided novel insight into molecular mechanisms of redox homeostasis and its role in hypoxia sensing. Heightened carotid body activity has been implicated in the pathogenesis of autonomic morbidities associated with sleep-disordered breathing, congestive heart failure, and essential hypertension. The enzymes that generate gas messengers and redox regulation by HIFs represent potential therapeutic targets for normalizing carotid body function and downstream autonomic output in these disease states.     

Responses of flexor alpha-motoneurones in cats anaesthetised with chloralose

Summary 1. Ninety flexor -motoneurones mainly belonging to the PBST nucleus were examined in 27 cats anaesthetised with 50 mg/kg chloralose. 2. A fairly uniform intracellular response pattern was recorded on stimulation of ipsilateral cutaneous and muscle afferent fibres. There was an early EPSP corresponding to the flexor reflex; a second EPSP (usually with spikes superimposed) was designated a chloralose EPSP as it was associated with the chloralose jerk discharge recorded from the peripheral nerve; finally a prolonged hyperpolarisation, frequently associated with a reduction in synaptic activity. 3. The chloralose EPSP was more susceptible to increases in stimulus frequency and small doses of barbiturate than the flexor reflex EPSP. 4. The prolonged hyperpolarisation was unaltered by increased intracellular chloride ion concentration, and was therefore unlikely to be an IPSP generated at the motoneurone soma. 5. On spinal cord section, the flexor reflex EPSP and a late and prolonged hyperpolarisation were still recorded. However, the chloralose EPSP and the chloralose jerk discharge recorded from the peripheral nerve were abolished.     

Quantal breathing frequency variation in halothane anaesthetised neonatal rats

We examined the changes in cardioventilatory synchronisation and breathing frequency variability that occur during early postnatal development in anaesthetised rats. Five-minute periods of heart rate and inspiratory timing data were recorded from 26 halothane anaesthetised, spontaneously breathing rats aged 2–14 days. The presence of cardioventilatory synchronisation was determined by examining the timing relationship between inspiratory onset and the preceding ECG R waves. We observed synchronisation at all ages, and the degree of synchronisation present (measured as the Shannon entropy of the interval between inspiration and the immediately preceding R wave) did not correlate with age. Frequent apnoeas were observed in the respiratory frequency time series. The duration of these apnoeas was close to either one or two times the duration of the immediately preceding breath. We suggest that these “dropped breaths” may be the consequence of a resetting of the respiratory oscillator just prior to initiation of the breath, or a gating process beneath the oscillator that intermittently blocks the mechanical initiation of breaths. Dropped breaths were seen commonly in rats up to 11 days of age, but rarely in 11–14-day old rats, and were not associated with the presence or absence of cardioventilatory synchronisation.     

Responses of extensor alpha-motoneurones in cats anaesthetised with chloralose

Summary 1. In cats anaesthetised with 50 mg/kg chloralose, 102 extensor a motoneurones were examined from hindlimb extensor nuclei. 2. On stimulation of ipsilateral cutaneous and muscle afferent fibres, many types of intracellular responses were recorded. In general, there was a flexor reflex IPSP and then a chloralose IPSP at the time of the chloralose jerk discharge recorded from flexor nerves. This was usually followed by a 50–75 msec depolarisation and finally a late, prolonged hyperpolarisation. 3. The chloralose IPSPs were more sensitive to increases in stimulus frequency than flexor reflex IPSPs and were abolished after spinal cord section. 4. The late prolonged hyperpolarisation was unaltered by increased chloride ion concentration within the cell and was often associated with a reduction in spontaneous synaptic noise.     

Peripheral blood flows during colorectal distension in anaesthetised dogs

Distension of the descending colon elicits reflex cardiovascular responses, including increases in heart rate and arterial blood pressure. To study the relative contribution of vasoconstriction in individual vascular beds to this reflex response, experiments were performed on seven dogs anaesthetised with chloralose and instrumented with electromagnetic flowmeters around the superior mesenteric, the left renal and the left external iliac arteries. The colorectal portion of the intestine was distended at constant pressure (36.6 mm Hg, 4.9 kPa mean; range 25–50 mm Hg, 3.3–6.7 kPa) with warm Ringer solution for periods of 2 min. After a set of control distensions, the experiments were performed whilst the reflex rise in arterial pressure was prevented by removal of blood from the arterial tree. In control distensions arterial pressure increased by 11.3±1.5 mm Hg, 1.51±0.12 kPa (mean±SEM). In distensions at constant arterial pressure, peripheral blood flows were altered to different extents in the three territories studied: vascular resistance increased by 30.8±5.6% (P<0.01) in the mesenteric, by 4.1±1.5% (P<0.03) in the renal, and by 15.2±6.8% (NS) in the external iliac bed. We conclude that colorectal distension may reflect activation of a function-specific pathway of the sympathetic nervous system, which leads to much greater vasoconstriction in the splanchnic circulation than in renal or musculocutaneous circulations.     

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.     

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.     

A system for investigating oesophageal photoplethysmographic signals in anaesthetised patients

The monitoring of arterial blood oxygen saturation in patients with compromised peripheral perfusion is often difficult, because conventional non-invasive techniques such as pulse oximetry (SpO2) can fail. Poor peripheral circulation commonly occurs after major surgery including cardiopulmonary bypass. The difficulties in these clinical situations might be overcome if the sensor were to monitor a better perfused central part of the body such as the oesophagus. A new oesophageal photoplethysmographic (PPG) probe and an isolated processing system have been developed to investigate the pulsatile signals of anaesthetised adult patients undergoing routine surgery. Measurements were made in the middle third of the oesophagus, 25 cm to 30 cm from the upper incisors. The AC PPG signals are sampled by a data acquisition system connected to a laptop computer. The signals recorded correspond to infrared and red AC PPGs from the middle third oesophagus and the finger. Preliminary results from 20 patients show that good quality AC PPG signals can be measured in the human oesophagus. The ratio of the oesophageal to finger AC PPG amplitudes was calculated for the infrared and red wavelengths for each patient. The mean (+/- standard deviation) of this ratio was 2.9 +/- 2.1 (n = 19) for the infrared wavelength and 3.1 +/- 2.4 (n = 16) for the red wavelength. The red and infrared wavelengths used are appropriate for pulse oximetry and this investigation indicates that the mid-oesophagus may be a suitable site for the reliable monitoring of SpO2 in patients with poor peripheral perfusion.     

Gaseous mediators in resolution of inflammation

There are numerous gaseous substances that can act as signaling molecules, but the best characterized of these are nitric oxide, hydrogen sulfide and carbon monoxide. Each has been shown to play important roles in many physiological and pathophysiological processes. This article is focused on the effects of these gasotransmitters in the context of inflammation. There is considerable overlap in the actions of nitric oxide, hydrogen sulfide and carbon monoxide with respect to inflammation, and these mediators appear to act primarily as anti-inflammatory substances, promoting resolution of inflammatory processes. They also have protective and pro-healing effects in some tissues, such as the gastrointestinal tract and lung. Over the past two decades, significant progress has been made in the development of novel anti-inflammatory and cytoprotective drugs that release of one or more of these gaseous mediators.     

Reverse arterial wall shear stress causes nitric oxide-dependent vasodilatation in the anaesthetised dog

The effects of a maintained increase in mean arterial wall shear stress (SS(m)) caused by blood flow in the normal and reverse direction on dilatation of the iliac artery were examined in the anaesthetised dog. Blood flow in the left iliac artery was varied in both the forwards and reverse directions by a perfusion pump connecting the right and left femoral arteries. An increase in blood flow, and therefore SS(m) in either direction, caused an increase in arterial diameter. However, an increase in forwards SS(m) (control 4.1+/-0.11 mm) caused a significantly greater change in arterial diameter than an equivalent increase in the reverse direction (control 4.3+/-0.08), 0.198+/-0.02 mm vs. 0.132+/-0.02 mm (mean+/-SEM) respectively, for the same increase in SS(m) (3.23 N/m(2)). The increase in arterial diameter in response to an increase in forwards or reverse SS(m) was attenuated by L-NAME (80 mg/kg i.v.), indicating that the arterial dilatation was mediated by nitric oxide (NO). These findings confirm that endothelial NO release is dependent on the steady-state SS(m) and that the response occurs irrespective of the direction in which this force is applied, but is attenuated in the reverse direction.     

Data interchange and related technologies in transfusion medicine

The transfusion medicine data interchange needs involve varying types of equipment and systems including blood collection and processing systems, component separation automation, laboratory instruments and automation systems (e.g. the ones used for screening of infectious markers), and various information management systems (e.g. laboratory information management systems donation/production management, and invoicing systems). Interfacing challenges and extra costs arise due to a lack of a common and open definition for the instrument interface, and a lack of a common conceptual framework for data interchange between systems and instruments. Standardization of data interchange is a need recognized by the end users and vendors. This is why the ISBT has launched a new Automated System Interface Task Force in September 2006 to establish a standard specification for transferring information between equipment and information management systems.     

Inhibition of neuronal nitric oxide reduces heart rate variability in the anaesthetised dog

In the vagally intact anaesthetised dog, we have investigated the role of nitric oxide (NO) on a normal sinus arrhythmia using an inhibitor of neuronally released NO, 1-(2-trifluoromethylphenyl) imidazole (TRIM). The mean and S.D. of the R-R interval was used to describe mean heart rate and heart rate variability, respectively. TRIM (0.8 mg I.C.) injected into the sinus node artery increased the mean heart rate slightly but reduced heart rate variability 3-fold from a control of 790 +/- 124 ms (mean +/- S.D.; n = 5) to 666 +/- 36 ms (P < 0.01 Student's paired t test, n = 5). These results suggest that neuronally released NO may have a vagal facilitatory role in the maintenance of sinus arrhythmia in the normal heart.