Respiratory responses to chemical pulses in the cerebrospinal fluid of cats

I The antihistamines mepyramine and halopyramine which have local anaesthetic properties, produced a rise in arterial blood pressure followed by a fall, similar to that seen with procaine, when perfused in a 10 mg/ml solution from the lateral ventricle to the cisterna magna in dogs. 2 The pressor response produced by procaine perfused through the cerebral ventricle is due to an action on structures situated in the caudal half of the floor of the fourth ventricle because a pressor response was obtained when a few microlitres of a 50 mg/ml solution of procaine were applied to a small area of the exposed floor of the fourth ventricle in a region 2 to 4 mm rostral to obex, and after cauterization of this area procaine perfused through the cerebral ventricles no longer raised arterial blood pressure. 3 Bilateral denervation of the carotid sinus did not affect the pressor response obtained with procaine perfused through the cerebral ventricles. 4 The pressor response to procaine is mediated through the sympathetic nervous system. It results partly from an increased adrenaline discharge from the adrenal glands and partly from increased sympathetic vasomotor tone, because the response is abolished or attenuated after removal of the adrenal glands and intravenous injections of hexamethonium and phentolamine.

Section: Introductionsupporting

confidence: 69%

Pressor Response Induced by Local Anaesthetics Perfused Through the Cerebral Ventricles of Dogs

Haranath

Indira-Narayan

Venkatakrishna‐Bhatt

1975

“…In cats, Miller, Stavraky & Woonton (1940) found changes in the electrocorticogram with physostigmine topically applied to the cerebral cortex, but not with pilocarpine. More recently, Borison, Haranath & McCarthy (1972) described differences in the effect of cholinomimetic substances on their perfusion through the cerebral ventricles of cats. Changes in respiration and blood pressure occurred with acetylcholine and methacholine, but not with pilocarpine.…”

Section: Discussionmentioning

confidence: 99%

A Central Vasodepressor Effect of Dyflos

Edery

Guertzenstein

1974

1 Cats were anaesthetized with pentobarbitone sodium and atropinized peripherally by intravenous injection of atropine methyl nitrate; the effect was examined of topical bilateral application of dyflos to the ventral surface of the medulla oblongata at a region lateral to the pyramids and caudal to the trapezoid bodies. Dyflos was applied by means of perspex rings; the volume of fluid placed in each ring was 10 gl.2 The topical application of dyflos (1-20 mg/ml) produced a fall in arterial blood pressure without changes in heart rate and, in experiments without artificial ventilation, tachypnoea with dissociation of thoracic and abdominal respiration. 3 Atropine methyl nitrate (50 mg/ml) applied topically in the same way as dyflos, prevented or abolished its vasodepressor effect. 4 The two reactivators of acetylcholinesterase, obidoxime (100-200 mg/ml) and pralidoxime mesylate (100-200 mg/ml), applied topically in the same way as dyflos, abolished its vasodepressor effect. The reactivator compound 30 (100 mg/ml), also a pyridinium aldoxime, did not have this effect. 5 Obidoxime and pralidoxime mesylate also reversed the vasodepression produced by carbachol applied to the ventral surface of the brain stem but not the vasodepression produced by glycine similarly applied. 6 The problem is discussed as to whether the reversal of the dyflos and carbachol-induced vasodepression by obidoxime and pralidoxime is due to acetylcholinesterase reactivation by dephosphorylation and decarbamylation respectively, to a central atropine-like action of these compounds or to a combination of both.

“…Elevation in blood pressure has been observed previously to occur in response to TTX as well as to procaine (Borison et al, 1963;Borison, Haranath & McCarthy, 1972). It provides a plausible explanation for the pulmonary oedema that was precipitated by TTX in awake cats, reported by us in an earlier investigation (Borison et al, 1963).…”

Section: Resultsmentioning

confidence: 64%

Respiratory and Circulatory Effects of Saxitoxin in the Cerebrospinal Fluid

Borison

McCarthy

1977

I In cats anaesthetized with pentobarbitone, saxitoxin and, on a few occasions, tetrodotoxin were injected into a lateral cerebral ventricle or into the subarachnoid space of the lower brain stem. Observations were made on frequency and tidal volume of breathing, on CO2 responsiveness and on electrical responsiveness of the respiratory centre. Effects on the blood pressure were observed simultaneously. 2 A single large dose of toxin, e.g., 250 ng, produced within minutes apneustic breathing and a rise in blood pressure which were converted rapidly to respiratory failure and hypotension. In contrast, repeated small doses, e.g., 25 ng, yielded only progressive slowing of the respiration together with circulatory hypotension. Bulbar depression was produced as effectively by subarachnoid injection as by intraventricular injection of the toxins. Onset of action was detectable within seconds. 3 Slowing of the respiration occurred independently of change in tidal volume and whether or not the vagus nerves were cut. The reduction in breathing frequency is attributed to direct toxin-induced depression of the central respiratory oscillator. 4 Steady-state measurements of tidal volume at controlled levels of alveolar CO2 pressure in intermediate stages of respiratory depression showed that the toxins produced an increase in CO2 stimulation threshold as well as a reduction in gain of CO2 responsiveness, whether or not the vagus nerves were cut. Carotid arterial chemoreceptor reactivity to 02 was demonstrable when central sensitivity to CO2 was depressed. These effects are attributed to a direct influence of the toxins upon the brainstem C02-tidal volume controller. SResponsiveness of the medullary inspiratory centre to electrical stimulation persisted after the failure of spontaneous breathing was caused by the toxins. Conversely, restitution of electrical responsiveness preceded the reappearance of spontaneous respiratory activity in the recovery phase of toxic depression. Circulatory effects paralleled the changes in respiratory behaviour. 6 On the basis of the relatively prompt and discrete alterations in the central respiratory and circulatory control mechanisms produced by saxitoxin and tetrodotoxin placed in the cerebrospinal fluid, it is concluded that the agents rapidly penetrated to deep target loci in the lower brain stem.