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316 Importance of Bulbar Autonomie Mechanisms in the Pentylenetetazol-Induced Cardiac Arrhythmias and Hypertension in Dogs
Abstracts of interest to ascertain whether Parsidol would preeminently block the EEG activation produced by low doses (0.1 mg/kg) of physostigmine or diisopropylfluorophosphate (DFP) in unanaesthrtized rabbits. In comparatively low dosage (l-2 mg/kg) intravenously, all of the phenothiazines induced a synchronous EEG pattern which was converted to an alert tracing by the cholinergic drugs. In higher doses (10 mg/kg), however, only Parsidol blocked completely the EEG effects of physostigmine or DFP indicating, together with marked mydriasis, significant anticholinergic actions. Experiments with o-amphetamine (l-5 mg/kg) show that all of the phenothiazincs tested reduce or antagonize the EEG and behavioural effects of this drug and that no marked distinction exists between the phenothiazines in this regard. Hence, the pharmacological data suggest that the antiparkinson action of Parsidol is exerted by means of a central anticholinergic effect. The report of White et nl.‘*’ showing that hyoscine ancl atropine, in that orcler of potency, block the EEG action of physostigmine and that chlorpromazine failed to manifest such a blockade fLtrther supports this suggestion. ,S,ll,,rorted Ly U.S.F.H.S. SentorResearchGmnt SF-LX.)
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93
Catecholamines were increased per cent of dogs. significantly during haemorrhage and transfusionparticularly in animals when acidosis was most severe. If -4.C.D. blood was titrated with trihydroxymethyl aminomethane (THAM) to an average pH of 7.56, rapid transfusion resulted in survival of 80 per cent of animals and return of catecholamincs to about control levrl‘i. Transfusion acidosis can also be prevented by maintenance of relatively normal artrrial pH with addition of Na,CO,. Simultaneous administration of CaCl, or addition of large concentrations of catecholamines to acid blood will also protect dogs against transfusion acidosis, mostly by maintaining adequate cardio-vascular function. 316 I mportanceofBulhar
-______ 1. (1956), /inn. Xew 2”or!i . Id. Sri., 64, 690. 2. \VHITE and BOYAJY (1960 1,.4rch. int. Pharmncodyz.,
127, 260.
315 Effect
on Plasma Catecholamine Concentration of Haemorrhage and pH Alteration Followed by Various Forms of Therapy. W. hf. MANGER, G. G. NAHAS, D. HASSAM and S. DUFTON (U.S.A.).
Haemorrhage of third or more of total blood volume in dogs was accompanied by increase in concentration of plasma catecholamines which was correlated with quantity of blood loss and severity of hypotension. Usually increase in epinephrine was considerably greater than norepinephrine. Slow haemorrhage caused smaller incrrases in catecholamines than rapid removal of the same quantity of blood. Further increases in catecholamines accompanied prolonged haemorrhagic hypotension. It seemed the principal factor activating the sympathetico-adrenal system was hypotension. However, hypotension following intravenous administration of histamine or egg white to sensitized dogs almost invariably caused smaller Increases m catecholammes than did the same degree 3 I7a of hypotension following haemorrhage. Replacement of blood loss with herparinized blood (even in dogs whose blood pressure was maintained at 50 mm Hg for 2: hr) usually resulted in restoration of blood pressure and catecholamines towards normal. Following rapid haemorrhage of about half blood volume, rapid transfusion with blood collected in acid citrate dextrose (A.C.D.) solution resulted in severe acidosis and death in 90
Autonomic Mechanisms in the Pentylenetetazol-Induced Cardiac Arrhythmias and Hypertension in Dogs. S. C. \VANG, K. P. BIRCHER and T. KAN,XI (U.S.A.).
It has been previously ascertained by stimulation and transection experiments that the sympathetic prcssor centre is located in the periventricular arca at the level of the medulla oblongata, and the vagal and sympathetic depressor ccntre is located caudally in the obcx. Contrary to the rcccnt claim of Peiss (1960) that reflex cardio-accelerator mechanism is located in the hypothalamus. our evidence indicates that cardio-acceleration can be reflexly elicited in animals without hypothalamus, and that the reflex mechanism for cardio-acceleration is also located in the medulla, in the same general region for the sympathetic pressor responses. These bulbar sympathetic and vagal mechanisms are important for the tachycardiac or bradycardiac arrhythmias and hypertension, induced by pentylenetetrazol given to succinylcholinized animals intravenously or into various crrebral ventricles. These cardiac responses can be readily prevented by protecting the heart from the effects of cmtrally mediated vagal and sympathetic outflows (vagotomy, 1-hyos-cyamine or N-ethyl-nortropine-benzydryl-ether; and complete sympathectomy, cervical chordotomy or dihydrogenated ergot alkaloids). The hypertensive responses, on the other hand, are not completely prevented by the above procedures. This evidence suggests the possibility of some constrictor action of pentylenetetrazol on the vascular system.
Recherches sur 1’Action Adrenalinogene de 1’1011 Potassium chez Differentes Especes A&males. R. HAZARD (France). Les premieres expCriences faites sur le chien (chloralosC)(l) ont montrC la nt!cessit& de rPaliser tm un temps donnC une certaine concentration du se1 de potassium dans le sang aff&ent de la surr&ale. L’injection dam la saph+ne de 0.015 g de KC1 par kg faite avec quelques p&cautions est en
of Papers
93
Catecholamines were increased per cent of dogs. significantly during haemorrhage and transfusionparticularly in animals when acidosis was most severe. If -4.C.D. blood was titrated with trihydroxymethyl aminomethane (THAM) to an average pH of 7.56, rapid transfusion resulted in survival of 80 per cent of animals and return of catecholamincs to about control levrl‘i. Transfusion acidosis can also be prevented by maintenance of relatively normal artrrial pH with addition of Na,CO,. Simultaneous administration of CaCl, or addition of large concentrations of catecholamines to acid blood will also protect dogs against transfusion acidosis, mostly by maintaining adequate cardio-vascular function. 316 I mportanceofBulhar
-______ 1. (1956), /inn. Xew 2”or!i . Id. Sri., 64, 690. 2. \VHITE and BOYAJY (1960 1,.4rch. int. Pharmncodyz.,
127, 260.
315 Effect
on Plasma Catecholamine Concentration of Haemorrhage and pH Alteration Followed by Various Forms of Therapy. W. hf. MANGER, G. G. NAHAS, D. HASSAM and S. DUFTON (U.S.A.).
Haemorrhage of third or more of total blood volume in dogs was accompanied by increase in concentration of plasma catecholamines which was correlated with quantity of blood loss and severity of hypotension. Usually increase in epinephrine was considerably greater than norepinephrine. Slow haemorrhage caused smaller incrrases in catecholamines than rapid removal of the same quantity of blood. Further increases in catecholamines accompanied prolonged haemorrhagic hypotension. It seemed the principal factor activating the sympathetico-adrenal system was hypotension. However, hypotension following intravenous administration of histamine or egg white to sensitized dogs almost invariably caused smaller Increases m catecholammes than did the same degree 3 I7a of hypotension following haemorrhage. Replacement of blood loss with herparinized blood (even in dogs whose blood pressure was maintained at 50 mm Hg for 2: hr) usually resulted in restoration of blood pressure and catecholamines towards normal. Following rapid haemorrhage of about half blood volume, rapid transfusion with blood collected in acid citrate dextrose (A.C.D.) solution resulted in severe acidosis and death in 90
Autonomic Mechanisms in the Pentylenetetazol-Induced Cardiac Arrhythmias and Hypertension in Dogs. S. C. \VANG, K. P. BIRCHER and T. KAN,XI (U.S.A.).
It has been previously ascertained by stimulation and transection experiments that the sympathetic prcssor centre is located in the periventricular arca at the level of the medulla oblongata, and the vagal and sympathetic depressor ccntre is located caudally in the obcx. Contrary to the rcccnt claim of Peiss (1960) that reflex cardio-accelerator mechanism is located in the hypothalamus. our evidence indicates that cardio-acceleration can be reflexly elicited in animals without hypothalamus, and that the reflex mechanism for cardio-acceleration is also located in the medulla, in the same general region for the sympathetic pressor responses. These bulbar sympathetic and vagal mechanisms are important for the tachycardiac or bradycardiac arrhythmias and hypertension, induced by pentylenetetrazol given to succinylcholinized animals intravenously or into various crrebral ventricles. These cardiac responses can be readily prevented by protecting the heart from the effects of cmtrally mediated vagal and sympathetic outflows (vagotomy, 1-hyos-cyamine or N-ethyl-nortropine-benzydryl-ether; and complete sympathectomy, cervical chordotomy or dihydrogenated ergot alkaloids). The hypertensive responses, on the other hand, are not completely prevented by the above procedures. This evidence suggests the possibility of some constrictor action of pentylenetetrazol on the vascular system.
Recherches sur 1’Action Adrenalinogene de 1’1011 Potassium chez Differentes Especes A&males. R. HAZARD (France). Les premieres expCriences faites sur le chien (chloralosC)(l) ont montrC la nt!cessit& de rPaliser tm un temps donnC une certaine concentration du se1 de potassium dans le sang aff&ent de la surr&ale. L’injection dam la saph+ne de 0.015 g de KC1 par kg faite avec quelques p&cautions est en