Simultaneous recordings of sympathetic activity in the right inferior cardiac nerve, and of baroreceptor activity in the common carotid baroreceptor nerve were made in cats with an isolated common carotid artery and sinus area.The effect of the change from non-pulsatile to pulsatile sinus pressure was to impose a rhythm synchronous with the pump upon sympathetic activity. The changes in amplitude of sympathetic activity were investigated.The inhibition of sympathetic activity by carotid traction was used to identify sympathetic fibres.The baroreceptor-sympathetic reflex delay was of the order of 200 m/sec. thus providing a beat to beat control of cardiac activity.WHEN baroreceptor activity is increased by raising the blood pressure by a variety of means, such as adrenaline, angiotensin, or a rapid intravenous injection of saline, sympathetic activity declines or ceases. This effect upon sympathetic activity is abolished by section of the buffer nerves [Adrian, Bronk and Phillips, 1932; Bronk, Ferguson and Soldant, 1934;Bronk et al., 1936;Gernandt, Liljestrand and Zotterman, 1946; Downing and Siegal, 1963]. Buffer nerve section also abolishes the cardiac rhythm associated with varying sympathetic activity, while at the same time causing an increase in the mean level of sympathetic discharge [Adrian, Bronk and Phillips, 1932;Bronk et al., 1936; Downing and Siegal, 1963]. It was further observed by Downing and Siegal [1963] that if a carotid sinus were perfused by a donor animal, and all other buffer nerves cut, sympathetic activity in the recipient changed from a rhythmic discharge synchronous with the animal's own heart to a rhythmic discharge synchronous with the cardiac rhythm of the donor animal.In this investigation we have recorded baroreceptor and sympathetic activity electroneurographically and have examined the effects upon sympathetic activity of pulsatile and non-pulsatile baroreceptor discharges. METHODS Forty-five cats, anaesthetized with intraperitoneal pentobarbitone (40-50 mg./kg. bodyweight) were used. The chest was opened by removing the anterior two-thirds of the first three ribs on the right, the animal receiving artificial respiration. Through this opening into the thorax the right inferior cardiac nerve was exposed. The activity from few or multi-fibre preparations of this nerve was picked up by saline wick electrodes connected to an AC-coupled amplifier and multi-beam oscilloscope, and recorded by a camera attached to the oscilloscope.
I Rat isolated diaphragm preparations were stimulated indirectly either intermittently at 20, 50 or 100 Hz or continuously at 0.2 Hz. 2 Addition of 1.8 gM paraoxon (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which undergoes slow spontaneous reactivation) for 5 min to the organ bath produced a failure of the muscle to maintain tetanic tension (tetanic fade, Wedensky inhibition) and potentiated the neuromuscular blocking activity of exogenous acetylcholine. The rates of recovery from both these effects were recorded. 3 In a series of experiments with dyflos (which inhibits acetylcholinesterase by forming a phosphorylated enzyme which does not undergo spontaneous reactivation) the relationship between functional acetylcholinesterase activity and neuromuscular blocking activity of exogenous acetylcholine was also determined. 4 From the data obtained, the relationship between functional acetylcholinesterase activity and tetanic fade was calculated. These calculations show that (i) a considerable reduction in functional acetylcholinesterase activity is required before the diaphragm loses its ability to respond with a sustained tetanus to indirect stimulation at higher frequencies, (ii) the minimum (critical) level of functional acetylcholinesterase activity required for a normal tetanic response is directly related to the frequency of stimulation and (iii) once functional acetylcholinesterase activity has been reduced to the critical level, a very small further reduction leads to a complete tetanic fade. 5 The meaning of functional acetylcholinesterase assays and of conclusions which can be drawn . from them, is discussed,
The existence of a chemoreceptor mechanism supplied by the pulmonary artery was demonstrated in the following manner.In aneesthetized cats or rabbits the main pulmonary artery was carmulated through the right ventricle. The right pulmonary artery was tied and the left pulmonary artery cannulated approximately 0 5 cm. from the bifurcation. The isolated pulmonary segment was perfusel at normal pressure and rate of blood flow. Reflex effects on respiration and sympathetic nervous efferent activity were studied by simultaneous perfusion of the systemic circulation at normal pressure and flow rate.Perfusion of the isolated pulmonary arterial segment with added NaCN caused increased afferent vagal activity. When the systemic circulation was perfused simultaneously and independently of the pulmonary arterial segment, anoxia or asphyxia of the pulmonary arterial perfusate caused reflex increase in the rate and depth of respiration and sympathetic activity. Hypercapnia of the pulmonary arterial blood had little effect in the presence of a high oxygen tension.THE existence of chemoreceptor tissue with a blood supply from the pulmonary artery has been in dispute for many years. Boyd [1961] reviewed the evidence for such a structure and described three groups of chemoreceptorlike tissue near the pulmonary artery in man. He termed these the aorticopulmonary bodies. The superior aortico-pulmonary body lies between the caudal surface of the aortic arch and the ligamentum arteriosum. The middle and inferior bodies lie respectively between the aorta and the pulmonary artery at the level of the bifurcation of the pulmonary artery and nearer the heart, Penitschka [1931] described an epitheloid structure between the aorta and the pulmonary artery which he termed the paraganglion aorticum supracardiale. Histological studies by Nonidez [1936] in kittens and one adult cat were in favour of a pulmonary arterial blood supply to this tissue. However, Goormaghtigh and Pannier [1936] showed that, whereas in foetal cats and new-born kittens the paraganglion derived blood from both the pulmonary artery and the left coronary artery, in adult animals the pulmonary arterial supply closed down. Nonidez [1937] later showed that in puppies there was no pulmonary arterial blood supply, as is the case in man [Boyd, 1961]. Further histological evidence is discussed by Cropp and Comroe [1961].Experimental evidence for chemoreceptor tissue supplied with blood from the pulmonary artery has also been lacking until now. The time relationship of the hyperpncea following the injection of cyanide into either the right or the left ventricle [Comroe, 1939] did not favour the presence of pulmonary chemoreceptors. Heymans and Heymans [1927] found no increase 164
Summary1. Tetramonoisopropyl pyrophosphortetramide (iso-OMPA) added for 15 min to the rat isolated phrenic nerve-diaphragm in a concentration of 30 /,M, produced a complete selective and stable inhibition of cholinesterase. A concentration of 3 /.M produced near complete inhibition of cholinesterase, and a concentration of 300 ,pM also inhibited acetylcholinesterase marginally.2. Inhibition of cholinesterase was associated with a sustained increase in the neuromuscular blocking action of exogenous butyrylcholine but not of exogenous acetylcholine. Iso-OMPA, 300 ,uM, in addition caused transient increases in the sensitivity of the rat diaphragm to exogenous acetylcholine and butyrylcholine. In the same concentration, it had a curare-like action on the frog rectus abdominis muscle preparation.3. Iso-OMPA, 30 ptM, caused reversible increases in the amplitude of the twitch response and tetanic responses, which were of a similar magnitude in the indirectly stimulated preparation and the directly stimulated curarized preparation. Caffeine had a similar effect on the twitch response and its effectiveness was increased by iso-OMPA, and vice-versa. Amongst anticholinesterases, octamethyl pyrophosphortetramide and tetraethylpyrophosphate also enhanced the amplitude of the tetanic response, but paraoxon, dyflos, and mipafox did not. 4. It is concluded that iso-OMPA, in concentrations (3 and 30 ,uM) which in 15 min give near maximal or maximal selective inhibition of cholinesterase, has no effect on the transmission of nerve impulses at the neuromuscular junction, but enhances reversibly the amplitude of the contractile response to stimulation by a direct action upon the muscle fibre, which involves a mechanism related to but not identical with that by which caffeine potentiates twitch tension. In higher concentrations, iso-OMPA has a curare-like action at the neuromuscular junction.
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