Circulation,respiration, and blood homeostasis in cyanide-poisoned dogs after treatment with 4-dimethylaminophenol or cobalt compounds

The effects of intravenously injected 4-dimethylaminophenol-HCl (DMAP), Co₂EDTA, and Co(histidine)₂ on the survival rate and several physiological parameters were studied on dogs after acute intravenous poisoning with the double lethal dose of potassium cyanide.All dogs survived when the antidotes were administered 1 min after poisoning. When the therapy began 4 min after poisoning more dogs were rescued in the DMAP group than in the cobalt groups. DMAP, Co₂EDTA, and Co(histidine)₂ restored circulation and respiration of the surviving animals in a similar manner.The increase in the plasma concentrations of glucose and lactate was much higher in the Co₂EDTA group than in the DMAP group. The injection of Co₂EDTA produced a sharp rise in the lactate-to-pyruvate ratio. The lactate-to-pyruvate ratio stayed unchanged for some 15 min after injection of DMAP before also rising. The total dose of KCN (4 mg/kg) was bound to the ferrihemoglobin formed by DMAP. The arterial pO₂ increase, caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin, was less when the cyanide could act on the tissues for a longer period of time before the therapy with DMAP began.DMAP is more appropriate for the therapy of cyanide poisoning than Co₂EDTA, since the latter adds its inhibitory effects on the metablism to those of cyanide.     

Cerebral blood flow,circulation, and blood homeostasis of dogs during slow cyanide poisoning and after treatment with 4-dimethylaminophenol

The effects of 4-dimethylaminophenol · HCl (DMAP) and 100% oxygen on cerebral blood flow (CBF) and peripheral circulation, arterial and venous blood gases, and other parameters have been investigated in dogs in the course of slow cyanide infusion.The i.v. infusion of KCN increased the respiratory minute volume, accompanied by a rise in arterial pO₂ and pH and a decrease in arterial pCO₂ while the venous lactate concentration increased by about 500% and the hemoglobin content and hematocrit by about 30%. Heart rate and carotid artery blood flow decreased. Local CBF in the cingulum as measured with thermocouples rose steadily, and the brain and oesophagus temperature were lowered. The breathing of 100% oxygen raised the local CBF, the temperature, and the arterial pCO₂.During the infusion of KCN into the femoral artery of artificially ventilated dogs the femoral venous pO₂ increased continuously by some 40 mm Hg, attended with a decrease in pCO₂ of 15 mm Hg. The femoral blood flow, however, rose sharply within 3 min. 100% oxygen induced a rise in pCO₂ and a diminution of pH in the femoral vein and in the sinus sagittalis, and the femoral flow rose rapidly.After DMAP i.v. the values of most of the parameters returned to normal or finally stabilized below or above the initial level. The rise in the hemoglobin content, hematocrit, and lactate concentration was stopped, but the arterial and venous pH remained or were lowered. DMAP elicited a rapid, strong decrease in the pO₂ of the femoral vein and the sinus sagittalis with a concomitant marked increase in pCO₂.     

Effects of 4-dimethylaminophenol and Co2EDTA on circulation,respiration, and blood homeostasis in dogs

The effects of intravenously injected 4-dimethylaminophenol and Co₂EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin.A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30–40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase.Co₂EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co₂EDTA. The side effects of Co₂EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.     

对二甲氨基酚治疗急性失血合并氰中毒对血液动力学及血液内环境的影响

本实验用犬制备了轻(10％)、中(15％)、重度(20％)急性失血合并ⅳ NaCN 2.5 mg/kg中毒的动物模型,观察了ⅳ DMAP 2.5mg/kg治疗时血液动力学及血液内环境的变化。结果发现,DMAP治疗轻度急性失血合并氰中毒能使心血管功能迅速恢复正常并维持稳定,随失血程度加重DMAP对心血管功能兴奋作用减弱;血气分析及HbFe~(3+)测定结果表明,DMAP治疗急性失血合并氰中毒可造成机体严重缺氧及代谢性酸中毒,并随失血程度的加重而加剧。     

Effects of amyl nitrite on circulation,respiration and blood homoeostasis in cyanide poisoning

The effects of intravenously (i.v.) administered or inhaled amyl nitrite (AN) were followed under chloralose anaesthesia in intact and cyanide-poisoned, spontaneously breathing beagles. The i.v. doses of AN were 0.03 and 0.15 mmol/kg and the i.v. dose of KCN was 0.06 mmol/kg. AN was inhaled in a closed system at 0.15 mmol/kg without previous poisoning and, in addition, at 0.074 mmol/kg (two ampoules at 0.3 ml AN) during artificial ventilation after poisoning with 0.045 mmol KCN/kg i.v., Mean arterial pressure decreased by 15 and 40 mmHg, respectively, after i.v. injection of AN, associated with bradycardia and lowered peripheral blood flow. Respiratory minute volume rose by 65% with the higher dose. Arterial pO₂ decreased by 20 mmHg while pCO₂ rose by 6 mmHg. Within 30 min of injection, these changes were only partially reversible. Similar results were obtained following inhalation of AN in a closed system. Lactic acidosis and lowering of pH were produced by the i.v. route, but not by inhalation. Total haemoglobin increased. The lethality of KCN was abolished with AN doses that produced 10–30% ferrihaemoglobin. Artificial ventilation and simultaneous inhalation of AN after poisoning with lethal doses of KCN turned out to be ineffective therapeutic measures. The findings are compared with those of other papers dealing with cyanide poisoning and AN. It is pointed out that, for the present, there is no experimental proof for another antidotal mechanism of action of AN than ferrihaemoglobin formation.     

Comparison of hydroxylamine, 4-dimethylaminophenol and nitrite protection against cyanide poisoning in mice

Intraperitoneal doses of 4-dimethylaminophenol hydrochloride (DMAP), hydroxylamine hydrochloride (H₂NOH) and sodium nitrite (NaNO₂) were found where each converted a maximum of about 37% of the total circulating hemoglobin in mice to methemoglobin. Those doses in mmol/kg were: 0.29 for DMAP, 1.1 for H₂NOH, and 1.1 for NaNO₂. For DMAP and H₂NOH the peak was sharp and at about 7 min after injection whereas for NaNO₂ the peak was much broader and at about 40 min. The i.p. LD₅₀'s in mmol/kg were: 0.48 for DMAP, 1.8 for H₂NOH and 2.3 for NaNO₂. When mice pretreated with each of the methemoglobin-generating agents were challenged with sodium cyanide, the ratios of the LD₅₀'s in protected mice to those in control mice (protection index, PI) were 1.5 for H₂NOH, 2.0 for DMAP and 3.1 for NaNO₂. When sodium thiosulfate was also given in combination with each of the three methemoglobin-generating agents, the protective effect was at least additive. The PI against sodium sulfide was also significantly greater in mice pretreated with NaNO₂ than in mice given H₂NOH. Methemoglobins generated from human and mouse hemoglobins by either NaNO₂ or by H₂NOH had identical binding affinities (dissociation constants) for cyanide. When human red cells containing methemoglobin generated by exposure to either NaNO₂ or H₂NOH were injected into the peritoneal cavity of mice and then followed by cyanide challenges, there was no difference in the PI for the two kinds of methemoglobin. Not only was the PI the same in each case with human cells, but it was also identical with that in mice given NaNO₂ systemically to generate the same total amount of methemoglobin. The difference in PI between NaNO₂ and H₂NOH (or DMAP) in mice appears to be related to the high rate of methemoglobin reductase activity in mouse RBC. It appears likely that cyanmethemoglobin is a substrate for mouse methemoglobin reductase activity, and that NaNO₂ is an inhibitor of mouse methemoglobin reductase. No differences in cyanide antagonism between NaNO₂ and H₂NOH would be anticipated in humans because of the slow rates of methemoglobin reduction in human red cells.     

Effects of 4-dimethylaminophenol and Co2EDTA on circulation, respiration, and blood homeostasis in dogs.

The effects of intravenously injected 4-dimethylaminophenol and Co2EDTA on peripheral circulation, respiration, acid-base balance, and several other physiological and biochemical parameters were studied on dogs. DMAP increased the respiratory minute volume and mean arterial pressure, diminished the lactate-to-pyruvate ratio, and induced an increase in arterial oxygen pressure caused by liberation of oxygen from oxyhemoglobin during the formation of ferrihemoglobin. A study in vitro of the fate of the oxygen during the reaction between DMAP and oxyhemoglobin showed that only 30--40% of the oxygen released by the formation of ferrihemoglobin appeared in the gas phase. Co2EDTA caused circulatory depression, hyperventilation, and metabolic acidosis resulting in a decrease in base-excess and pH. The concentrations of lactate, pyruvate, potassium, and urea nitrogen and the hemoglobin content were increased by Co2EDTA. The side effects of Co2EDTA in therapeutic doses were more serious than those of DMAP. Thus the latter is superior in the therapy of cyanide poisoning, all the more since it detoxifies more cyanide.     

Antagonism of the Lethal Effects of Cyanide by a Synthetic Water-Soluble Cobalt(IlI) Porphyrin Compound

Efficacy of hydroxocobalamin (vitamin B₁₂) as a cyanide antidoteis limited by its high molecular weight (1355 g/mol) and bythe competitive binding of the cobalamin dimethylbenzimida zole.The present study describes experiments with a lower molecularweight cobalt porphyrin that has a high affinity for cyanide,Co(III)-5,10,15,20-tetrakis(4-sulfonatophenyl) porphyrin (CoTPPS),which was prepared by the method of Herrmann et al. (1978).CoTPPS was synthesized and its efficacy as an anti dote to thelethal effects of cyanide either alone or in various combinationswith NaNO₂ and/or Na₂S₂O₃ was determined. The LD5O value forCoTPPS was found to be 334 mg/kg. These studies were conductedusing the CoTPPS LD01, 200 mg/kg. The cyanide antagonists NaNO(0.1 g/kg, sc), Na₂S₂O₃ (1.0 g/kg, ip), and CoTPPS (0.2 g/kg,ip) were administered at 45, 15, and 10 min respectively priorto graded doses of KCN (Sc). The LD50 values for KCN in maleSwiss-Webster mice were calculated by probit analysis at the95% confidence level and the various treatments were comparedby potency ratios. These results indicated that the administrationof CoTPPS alone protects against the lethal effects of cyanide.Moreover, CoTPPS adds to the protection provided by Na₂S₂O₃and/or NaNO² Efficacy of this antidote is probably related tothe binding equilibrium between CoTPPS and cyanide.     

Zur Beurteilung der Blausäure-Antidote

The effect of various antidotes on the exhalation of hydrocyanic acid has been measured in guinea pigs and cats poisoned with cyanide. This procedure permits evaluation of both the speed of action and the capacity of the agents tested to detoxify hydrocyanic acid, and therefore allows an exact judgement as to therapeutic value of various antidotes to cyanide poisoning. The results were as follows:

1. Cobaltous histidine at a dose of 20 mg/kg was distinguished among the compounds tested by its rapid action in both species. Its detoxifying capacity was not adequate however. Treatment of severe cyanide poisoning in man with Co (his)₂ would appear to be reasonable, but only when combined with sodium thiosulfate.
2. The same rapid action as with cobaltous histidine was achieved in cats by intravenous injection of 2.25 mg/kg p-dimethylaminophenole (DMAP) leading to a methemoglobin formation of 30%. A dose of 0.75 mg/kg DMAP forming 10% methemoglobin reduced HCN-exhalation by an equivalent amount only after a 2.4 min delay. The capacity of DMAP to detoxify hydrocyanic acid was considerably greater than that of cobaltous histidine but still was far inferior to that of sodium thiosulfate.
3. The high capacity of sodium thiosulfate to detoxify hydrocyanic acid was likewise demonstrated by the new method employed here in both animal species. However, the onset of its effect was always very delayed. In clinical practice, this agent should never be omitted, but in treatment of severe poisonings it will only be successful when combined with a more rapid-acting antidote such as cobaltous histidine or DMAP.
4. Sodium nitrite, even when applied in relatively high doses, did not act rapidly enough nor did it demonstrate a satisfactory capacity to detoxify hydrocyanic acid. Therefore, it no longer fulfills the requirements that presently should be demanded of an antidote to hydrocyanic acid.

     

The effect of prior treatment with 4-dimethylaminophenol (DMAP) on animals experimentally poisoned with hydrogen cyanide

Six dogs were given sufficient oral 4-dimethylaminophenol (DMAP) to produce a peak methaemoglobin level of 12–15%. Five out of the six dogs then survived an intravenous injection of approximately 2 LD₅₀'s of hydrogen cyanide given when the methaemoglobin had reached 8–10%. The sixth dog died after 44 min. When the same dose of hydrogen cyanide was given to dogs, not previously given DMAP, all three died within 11/2 min. It was concluded that prior treatment with oral DMAP provided a large measure of protection against cyanide poisoning. Comparison of cyanide levels in whole blood and plasma in the two groups of dogs lent support to the hypothesis that methaemoglobin complexed with cyanide in the erythrocytes causing the plasma cyanide to remain lower than it did in unprotected animals.     

The effects of honey bee (Apis mellifera L.) venom and two of its constituents,melittin and phospholipase A2, on the cardiovascular system of the rat

The cardiovascular effects of whole lyophilised honey bee venom and its major constituents, melittin and phosphatidate 2-acylhydrolase, EC 3.1.1.4 (phospholipase A₂) have been studied in the anaesthetised rat and on the isolated perfused rat heart. Single bolus injections of whole venom (5–20 μg) irreversibly paralysed the isolated heart in 30–60 sec; perfusion of lower concentrations (1–8 μg/g tissue/min) caused paralysis over longer periods. In the whole animal, bee venom produced two differing responses on blood pressure depending on resting levels. In animals with a mean blood pressure of 95/67 mmHg, venom (0·5 mg/kg body weight) caused an increase of about 20 mmHg in 30 sec; in animals with a mean blood pressure of 138/112 mmHg, venom (0·7 mg/kg body weight) caused a marked fall. In both cases blood pressure returned to pre-venom levels after 5 min. Electrocardiographic changes were noted 15–20 min after envenomation, principally T wave elevation followed by ST-segment depression. The majority of these effects can be ascribed to the main constituents of honey bee venom; melittin (20–40 μg) irreversibly paralysed the isolated heart in 37–64 sec, phospholipase A₂ was inactive. In the anaesthetised animal, melittin (200 μg/kg) slightly increased blood pressure but did not invariably affect ECG, whereas phospholipase A₂ was profoundly hypotensive. The cardiotoxicity of melittin was less marked in the whole animal.     

Effects of benidipine, a long-lasting dihydropyridine-Ca2+ channel blocker, on cerebral blood flow autoregulation in spontaneously hypertensive rats

Chronic hypertension shifts cerebral blood flow (CBF) autoregulation towards higher blood pressure. We examined whether or not benidipine, a long-lasting dihydropyridine calcium channel blocker (CCB), improves the CBF autoregulation in spontaneously hypertensive rats (SHRs). CBF was analyzed by laser-Doppler flowmetry during stepwise hypotension by controlled bleeding. The lower limit of CBF autoregulation was calculated as the mean arterial blood pressure at which CBF decreased by 10% of the baseline. Mean arterial blood pressure and cerebral vascular resistance in SHRs were higher than those in normotensive Wistar rats. Oral administration of benidipine (3 mg/kg) for 8 d lowered the mean arterial blood pressure and cerebral vascular resistance, which were equivalent to the effects of amlodipine (3 mg/kg), another CCB, or candesartan (1 mg/kg), an Angiotensin II type-1 receptor blocker. The lower limit of CBF autoregulation in SHRs (142+/-4 mmHg) was significantly shifted to a higher-pressure level compared with Wistar rats (59+/-2 mmHg). The lower limit of CBF autoregulation was significantly lower in the benidipine-treated group (91+/-4 mmHg) than that in the control SHRs, and similar to that of the amlodipine group (97+/-6 mmHg). Benidipine reduced the lower limit of CBF autoregulation more effectively than candesartan (109+/-4 mmHg). In conclusion, benidipine shifted the limit of CBF autoregulation towards lower blood pressure in SHRs under hypotensive conditions by hemorrhage. These results suggest that benidipine may be useful for the treatment of hypertensive patients with the elderly or cerebrovascular disorders, in whom autoregulation of CBF is impaired.     

Increased juxtamedullary blood flow on stimulation of intrarenal prostaglandin biosynthesis

Regional blood flow distribution in the rabbit kidney was studied with radioactive microspheres before and during infusion of sodium arachidonate (C20:4). C20:4 (15–25 μg/kg/min) increased the ratio of juxtamedullary to superficial cortical blood flow by 12 ± 2.3% (n = 7) and caused an increase of 50 ± 15% (n = 5) in the output of urinary prostaglandins, mainly prostaglandin E₂. Indomethacin (10–20 mg/kg) given before the C20:4 infusion (n = 4) decreased the ratio of juxtamedullary to superficial cortical blood flow by 22 ± 7% and decreased the output of urinary prostaglandins. The results provide evidence for a role of prostaglandin E₂ as an intrarenal hormone regulating the inner cortical and medullary circulation of blood flow.     

Reduction of teratogenic effects of ethylenethiourea in rats by interaction with sodium nitrite in vivo

Nitrites are present in a wide variety of foods and their daily intake in man has been estimated at 1·5 mg. Ethylenethiourea (ETU), a major food contaminant resulting from degradation of ethylenebisdithiocarbamate fungicides, is a potent rat teratogen. The co-administration of ETU (60 or 40 mg/kg) and NaNO₂ (80 mg/kg) to rats by gavage on day 15 of gestation resulted in a higher survival of progeny than occurred with the corresponding dose of ETU alone. In a second study, ETU (60 mg/kg) and NaNO₂ (80, 100 or 120 mg/kg) were administered, either individually or in combination, as a single dose on day 13 of gestation. Administered alone, NaNO₂ did not produce any teratogenic response in full-term foetuses, whereas ETU produced a high incidence of various anomalies. However, the combined dosing resulted in the elimination of almost all the anomalies. The reducing effect of NaNO₂ on ETU-induced malformations was reversed when the animals were pretreated with 200 mg ascorbic acid/kg or 360 mg sodium ascorbate/kg. Since both of these are well-known inhibitors of N-nitrosation reactions, it was presumed that the simultaneous oral dosing of ETU and NaNO₂ resulted in the formation of N-nitrosoethylenethiourea.     

Effects of carvedilol on cerebral blood flow and its autoregulation in previous stroke patients with hypertension

We studied the effects of oral carvedilol (20 mg/day) on cerebral blood flow (CBF) and CBF autoregulation in ten previous stroke patients with hypertension. Measurement of CBF was done by the argon inhalation method. CBF autoregulation was also studied by the (A-V)O₂ method after stepwise reduction in systemic blood pressure. After 1 week of carvedilol administration, the mean arterial blood pressure showed an 18% decrease, with no significant changes in CBF, CBF autoregulation, or other cerebral circulation parameters. From these findings, it can be said that carvedilol is a potent anti-hypertensive agent that does not affect cerebral circulation parameters.     

对二甲氨基酚,依地酸二钴和亚硝酸钠对犬心脏血流动力学的影响

本文观察了DMAP,Co_2 EDTA和NaNO_2对犬心脏血流动力学的影响。iv DMAP 3.2mg/kg后LVP及其±dP/dtmax短暂轻度增加,CI,MAP,TPVR,LVWI和HR在30 min内基本稳定,至60 min时CI,LVWI和-dp/dtmax下降。iv Co_2EDTA 15mg/kg或NaNO_2 20 mg/kg后10 min MAP,CI,LVWI,LVP,±dP/dtmax及TPVR(Co_2EDTA组除外)降低最明显,60 min时NaNO_2组CI,MAP,TPVR,LVP和LVWI及Co+2EDTA组CI和LVWI仍然下降。Co_2EDTA组TPVR 1min时下降,5 min见恢复,60min上升。表明(1)DMAP能维持血压和外周血管张力平稳,使心脏舒缩性能短暂轻度增强;(2)Co_2EDTA初期降压系由其扩张血管和抑制心功能所致,后期降压主要由后者引起;(3)NaNO_2降压作用系通过扩张外周血管和抑制心功能所致。     

Pharmacokinetics of cyanide in poisoning of dogs,and the effect of 4-dimethylaminophenol or thiosulfate

Cyanide in blood, plasma, and urine of dogs after administration of K¹⁴CN was determined with the isotope dilution technique. The addition of large amounts of inactive KCN as soon as possible to a sample to be analyzed inhibited the decrease of the original cyanide concentration.After administration of several lethal doses of cyanide into the stomach or by slow intravenous infusion a concentration of about 40 M cyanide in plasma was found at the moment of respiratory arrest. Since 60% of the cyanide in plasma was bound to proteins the concentration of free cyanide which stopped respiration was about 16 M.Quick formation of ferrihemoglobin by i.v. injection of 4-dimethylaminophenol after plasma cyanide had risen to or above 40 M decreased the cyanide concentration in plasma and restored respiration, while cyanide was accumulated in red cells by formation of ferrihemoglobin cyanide.Equilibrium constants calculated for the reaction between ferrihemoglobin and cyanide in vivo indicated that the reaction approached equilibrium in a few minutes.Up to 60% of the radioactive cyanide absorbed was found as non-cyanide radioactivity in the urine.Abbreviations Used DMAP 4-Dimethylaminophenol hydrochloride - HbFe²⁺ Ferrohemoglobin - HbFe³⁺ Ferrihemoglobin - HbFe³⁺CN^– Ferrihemoglobin cyanide - C_a Molarity of all radioactive compounds calculated on the assumption that one mole cyanide yields one mole metabolite - NCR Molarity of non-cyanide radioactive compounds calculated on the assumption that one mole cyanide yields one mole of metabolite (C_a-[CN^–])     

Selective effects of lomerizine, a novel diphenylmethylpiperazine Ca2+ channel blocker, on cerebral blood flow in rats and dogs

1. In the present study we examined the effects of a new Ca2+ channel blocker (lomerizine), an antimigraine drug, on cerebral cortical blood flow (CBF) in anaesthetized rats (laser Doppler flowmetry) and on vertebral blood flow in anaesthetized beagle dogs (electromagnetic flowmeter). 2. Lomerizine (1.25-10 mg/kg, p.o.) dose-dependently increased CBF in rats without affecting blood pressure (BP) or heart rate (HR). 3. The plasma concentration of lomerizine (free base) in anaesthetized rats at 30 and 60 min after the initial administration of 5 mg/kg, p.o., time at which there was a significant increase in CBF, was similar to that reported in healthy subjects receiving lomerizine at 10 mg (2 x 5 mg)/day, p.o., a dose that significantly reduces the frequency and mean duration of headache attacks. 4. Flunarizine (10 mg/kg, p.o.) did not increase CBF significantly. Flunarizine (20 mg/kg, p.o.) did not increase CBF, but did decrease BP 30-120 min after its administration. 5. Lomerizine (2.5 and 5 mg/kg, intraduodenally) dose-dependently increased vertebral blood flow in dogs without significantly changing BP or HR. With 10 mg/kg intraduodenal lomerazine, vertebral blood flow remained elevated from 20 to 240 min after administration and BP was decreased from 20 to 120 min. 6. Thus, lomerizine had a greater effect on CBF than on BP and HR and, therefore, it may be clinically effective in conditions associated with circulatory disturbances in the brain, such as migraine, without producing systemic effects (e.g. hypotension) generally seen with other Ca2+ channel blockers.     

Dextroamphetamine-induced changes in regional cerebral blood flow

Regional cerebral blood flow (CBF), blood pressure, pulse rate, respiratory rate, end-tidal carbon dioxide and mood states were measured before and after IV injections of 15 mg dextroamphetamine sulfate or saline in 22 physically and mentally healthy normal volunteers. Amphetamine administration was associated with significant increases in systolic blood presure and vigor and decrease in end-tidal carbon dioxide. There were no significant differences between the amphetamine and saline groups on CBF changes. However, there was a non-significant trend towards a post-amphetamine CBF reduction, even after the flow values were corrected for the acute changes in CO₂.     

Der Einfluß von Kobaltgluconat und des Dikobaltsalzes der Äthylendiamintetraessigsäure (Co2EDTA) auf den Hirnstoffwechsel normaler und cyanidvergifteter Mäuse

Zusammenfassung An weißen Mäusen wurde die cyanidantagonistische Wirkung von Kobaltgluconat und Co₂-EDTA untersucht. 5 mg/kg Kobaltgluconat verhinderten sicher die äußeren Zeichen einer durch 1,75 mg/kg KCN i.v. hervorgerufenen Vergiftung. Die Schutzwirkung von 5 mg/kg Co₂-EDTA war unsicherer. Durch beide Verbindungen wurde die durch KCN verursachte Steigerung der Glykolyse und die Einschränkung der Energieproduktion im Gehirn abgeschwächt, aber nicht völlig aufgehoben. Die Restitution des veränderten Metabolitgehalts wurde beschleunigt. Beide Kobaltverbindungen riefen keine äußerlich erkennbaren Vergiftungssymptome hervor, führten aber zu Änderungen im Metabolitgehalt des Gehirns, die für eine Einschränkung des Kohlenhydrat- und Energiestoffwechsels sprechen.Folgende Abkürzungen werden in dieser Arbeit verwendet: ADP: Adenosindiphosphat, AMP: Adenosinmonophosphat, ATP: Adenosintriphosphat, Cyt.Ox.: Cytochromoxydase, KrP: Kreatinphosphat, P: anorganisches Orthophosphat.