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Anesthesiology Mar 1987In vitro release of cyanide from sodium nitroprusside in 5% dextrose in water solution following exposure or non-exposure to fluorescent light (500 ft candles or 791...
In vitro release of cyanide from sodium nitroprusside in 5% dextrose in water solution following exposure or non-exposure to fluorescent light (500 ft candles or 791 microwatt per square cm [muWcm-2]), was measured by a cyanide-specific ion electrode at 4, 8, 24, 48, and 72 h. The cyanide concentrations were significantly increased at 24 h in the light-exposed solution. In this group, 100% of the cyanide was released from sodium nitroprusside at 72 h exposure to light. However, cyanide concentrations showed no significant changes for 72 h in the light-protected solutions, which were either exposed to 500 foot candles fluorescent light or stored in a dark room. Less than 2.5% of the cyanide was released from sodium nitroprusside at 72 h in both of the light-protected groups. No significant differences in cyanide concentrations were observed at 8 h among the exposed or non-exposed solutions. After 24 h of exposure, the cyanide concentrations in the exposed group were significantly higher than those of the two light-protected solutions. However, there were no significant differences between the cyanide concentration in the light-protected solutions. These results substantiate the safety of sodium nitroprusside solution for 24 h if the sodium nitroprusside containing solutions are properly protected from light. An additional study performed showed that a significant amount of cyanide released from sodium nitroprusside was adsorbed to the surface of polyvinylchloride.
Topics: Cyanides; Drug Stability; Ferricyanides; Light; Nitroprusside; Risk; Time Factors
PubMed: 3826696
DOI: 10.1097/00000542-198703000-00019 -
Neuroscience Aug 1996Recent findings suggest that carotid chemoreceptor input into the ventral medullary surface intermediate area during hypoxia is inhibitory (Gozal et al., (1994)...
Recent findings suggest that carotid chemoreceptor input into the ventral medullary surface intermediate area during hypoxia is inhibitory (Gozal et al., (1994) Neurosci. Lett. 178, 73-76. However, systemic hypoxia is a complex stimulus, and effects of carotid chemoreceptor stimulation per se on intermediate ventral medullary surface neuronal activity are difficult to isolate. Therefore, we studied neural activation of the intermediate ventral medullary surface during peripheral chemoreceptor stimulation by intravenous sodium cyanide using optical procedures in seven pentobarbital-anesthetized cats. Control recordings were also acquired in the suprasylvian cortex of three cats. Images of reflected 660 nm light were collected at l/s with a charge-coupled device camera, triggered by the cardiac R wave, after 0.0, 0.5, 2, 5, 10, 20 and 40 micrograms/kg i.v. sodium cyanide administration before and following carotid sinus denervation. Sodium cyanide doses > 5 micrograms/kg significantly increased ventilation, an effect which was eliminated following carotid sinus denervation. A pronounced, dose-dependent activity decrease within the intermediate ventral medullary surface occurred within seconds of sodium cyanide administration, with subsequent return to baseline. Carotid sinus denervation eliminated rapid-onset neural responses to all sodium cyanide doses. However, at the 40 micrograms/kg dose, a smaller, slower onset (25 s), activity decrease occurred both pre- and postdenervation. In the neocortex, the sodium cyanide-induced fast responses were absent. Intravenous cyanide, acting via a carotid sinus nerve pathway, results in a dose-dependent decrease in neural activity within the intermediate ventral medullary surface of cats. High-dose sodium cyanide also appears to decrease intermediate ventral medullary surface neural activity directly.
Topics: Animals; Carotid Arteries; Cats; Cerebral Cortex; Chemoreceptor Cells; Denervation; Female; Heart; Male; Medulla Oblongata; Neurons; Optics and Photonics; Respiration; Sodium Cyanide; Vagotomy
PubMed: 8809818
DOI: 10.1016/0306-4522(96)00112-1 -
British Journal of Anaesthesia Feb 1987Brain cytochrome oxidase activity was measured after the in vitro addition of potassium cyanide (KCN) or sodium nitroprusside (SNP). Activity of cytochrome oxidase was...
Brain cytochrome oxidase activity was measured after the in vitro addition of potassium cyanide (KCN) or sodium nitroprusside (SNP). Activity of cytochrome oxidase was sensitive to KCN; however, this activity was unaffected by SNP. In SNP- and KCN-treated animals brain cytochrome oxidase activities were measured. At 3 min after SNP injection, inhibition of the enzymatic activity was the same as 1 min after KCN injection. Time to death for SNP-treated animals was longer than for KCN-treated animals. These data suggest that cyanide was released in vivo from SNP and that time was necessary for this release to occur.
Topics: Animals; Brain; Cyanides; Electron Transport Complex IV; Ferricyanides; Lethal Dose 50; Male; Mice; Mice, Inbred ICR; Nitroprusside; Potassium Cyanide; Time Factors
PubMed: 3030385
DOI: 10.1093/bja/59.2.236 -
The Journal of Physiology Apr 2006Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle fibres. We have now employed this difference to study mechanisms of skeletal muscle...
Isolated whole skeletal muscles fatigue more rapidly than isolated single muscle fibres. We have now employed this difference to study mechanisms of skeletal muscle fatigue. Isolated whole soleus and extensor digitorum longus (EDL) muscles were fatigued by repeated tetanic stimulation while measuring force production. Neither application of 10 mm lactic acid nor increasing the [K(+)] of the bath solution from 5 to 10 mm had any significant effect on the rate of force decline during fatigue induced by repeated brief tetani. Soleus muscles fatigued slightly faster during continuous tetanic stimulation in 10 mm[K(+)]. Inhibition of mitochondrial respiration with cyanide resulted in a faster fatigue development in both soleus and EDL muscles. Single soleus muscle fibres were fatigued by repeated tetani while measuring force and myoplasmic free [Ca(2+)] ([Ca(2+)](i)). Under control conditions, the single fibres were substantially more fatigue resistant than the whole soleus muscles; tetanic force at the end of a series of 100 tetani was reduced by about 10% and 50%, respectively. However, in the presence of cyanide, fatigue developed at a similar rate in whole muscles and single fibres, and tetanic force at the end of fatiguing stimulation was reduced by approximately 80%. The force decrease in the presence of cyanide was associated with a approximately 50% decrease in tetanic [Ca(2+)](i), compared with an increase of approximately 20% without cyanide. In conclusion, lactic acid or [K(+)] has little impact on fatigue induced by repeated tetani, whereas hypoxia speeds up fatigue development and this is mainly due to an impaired Ca(2+) release from the sarcoplasmic reticulum.
Topics: Action Potentials; Animals; Biological Transport; Calcium; Diffusion; Hypoxia; Lactic Acid; Male; Mice; Mice, Inbred Strains; Muscle Fatigue; Muscle Fibers, Skeletal; Muscle, Skeletal; Oxygen; Potassium; Sarcoplasmic Reticulum; Sodium Cyanide; Time Factors
PubMed: 16455685
DOI: 10.1113/jphysiol.2005.104521 -
Anesthesiology Mar 1977Thirty-nine dogs (including eight from a previous study) were given during a one-hour infusion either low (less than 1.0 mg/kg) or high doses (greater than 1.0 mg/kg) of...
Thirty-nine dogs (including eight from a previous study) were given during a one-hour infusion either low (less than 1.0 mg/kg) or high doses (greater than 1.0 mg/kg) of sodium nitroprusside in the presence or absence of circulating methemoglobin. In animals given low doses, the metabolic effects were relatively mild and consistent with those accounted for by a reduction in arterial pressure to 40 torr. In animals given high doses (with the same arterial pressure), metabolic alterations were significantly magnified and oxygen extraction was decreased. Animals pretreated with methemoglobin and given high doses of nitroprusside (again at the same arterial pressure) showed no toxic effect of nitroprusside. In separate studies, blood and tissue levels of cyanide were measured in dogs given high doses of nitroprusside (2.5-3.5 mg/kg) in the presence or absence of methemoglobin. In dogs given methemoglobin, 60 per cent of the administered cyanide (as nitroprusside) was recovered in the blood (as cyanmethemoglobin) after a one-hour infusion. Thereafter, blood cyanide levels declined over three hours to 25 per cent of peak levels, presumably by conversion to thiocyanate, since tissue levels of cyanide were negligible. In dogs not given methemoglobin, blood cyanide levels qualitatively followed a similar pattern but quantitatively were a fourth to a third those of pretreated dogs, and tissue levels of cyanide became elevated. It is concluded that in the dog nitroprusside, acutely administered, causes cyanide toxicity at doses exceeding 1.0-1.5 mg/kg, that the release of cyanide from nitroprusside in blood is rapid and in large quantities, that detoxification (presumably by conversion of cyanide to thiocyanate) is likewise fairly rapid but insufficient to prevent toxicity, and that protection is provided by methemoglobin.
Topics: Animals; Blood Pressure; Brain Chemistry; Cyanides; Dogs; Ferricyanides; Lactates; Methemoglobin; Nitroprusside; Thiocyanates; Time Factors
PubMed: 842873
DOI: 10.1097/00000542-197703000-00007 -
Chemical Research in Toxicology Dec 2012The formation of Co(III)TMPyP(CN)(2) at pH 7.4 has been shown to be completely cooperative (α(H) = 2) with an association constant of 2.1 (±0.2) × 10(11). The...
The formation of Co(III)TMPyP(CN)(2) at pH 7.4 has been shown to be completely cooperative (α(H) = 2) with an association constant of 2.1 (±0.2) × 10(11). The kinetics were investigated by stopped-flow spectrophotometry and revealed a complicated net reaction exhibiting 4 phases at pH 7.4 under conditions where cyanide was in excess. The data suggest molecular HCN (rather than CN(-)) to be the attacking nucleophile around neutrality. The two slower phases do not seem to be present when cyanide is not in excess, and the other two phases have rates comparable to that observed for cobalamin, a known effective cyanide scavenger. Addition of bovine serum albumin (BSA) did not affect the cooperativity of cyanide binding to Co(III)TMPyP, only lowered the equilibrium constant slightly to 1.2 (±0.2) × 10(11) and had an insignificant effect on the observed rate. A sublethal mouse model was used to assess the effectiveness of Co(III)TMPyP as a potential cyanide antidote. The administration of Co(III)TMPyP to sodium cyanide intoxicated mice resulted in the time required for the surviving mice to right themselves from a supine position being significantly decreased (9 ± 2 min) compared to that of the controls (33 ± 2 min). All observations were consistent with the demonstrated antidotal activity of Co(III)TMPyP operating through a cyanide-binding (i.e., scavenging) mechanism.
Topics: Animals; Antidotes; Cyanides; Male; Metalloporphyrins; Mice
PubMed: 23148604
DOI: 10.1021/tx300327v -
The Journal of Physiology Oct 19991. The effects of nitric oxide (NO) donors on whole-cell, TTX-sensitive sodium currents and single sodium channels in excised patches were examined in rat hippocampal...
1. The effects of nitric oxide (NO) donors on whole-cell, TTX-sensitive sodium currents and single sodium channels in excised patches were examined in rat hippocampal neurons. The whole-cell sodium current consisted of a large transient component (INa,t) and a smaller, inactivation-resistant, persistent component (INa,p). 2. In acutely dissociated neurons, the amplitude of the whole-cell INa, p increased by 60-80 % within a few minutes of exposure to either of two NO donors, sodium nitroprusside (SNP, 100 microM) or S-nitroso-N-acetyl-DL-penicillamine (SNAP, 100 microM). 3. The amplitude of INa,t was not changed significantly by the same concentrations of SNP and SNAP, indicating that NO had a selective effect on INa,p. 4. Both NO donors significantly increased the mean persistent current in excised inside-out patches from cultured hippocampal neurons. SNP at 10-100 microM increased average mean persistent current at a pipette potential (Vp) of +30 mV from -0.010 +/- 0.014 pA (control) to -2.91 +/- 1.41 pA (n = 10). SNAP at 3-100 microM increased the average mean inward current in six inside-out patches from -0.07 +/- 0.02 to -0.30 +/- 0.08 pA (Vp = +30 mV). 5. The increase in persistent Na+ channel activity recorded in inside-out patches in the presence of SNP or SNAP could be reversed by the reducing agent dithiothreitol (DTT, 2-5 mM) or by lidocaine (1-10 microM). 6. The average mean current recorded in the presence of SNP was 10-fold higher than that elicited by SNAP. The time delay before an increase was observed was shorter with SNP (4.0 +/- 0.8 min, n = 8) than with SNAP (8.4 +/- 1.6 min, n = 7). 7. A component of the SNP molecule added on its own, 5 mM sodium cyanide (NaCN), increased mean current in excised inside-out patches (Vp = +30 mV) from -0.06 +/- 0.04 to -0.58 +/- 0.21 pA (n = 19). This increase in channel activity could be blocked by 10 microM lidocaine and 2-5 mM DTT. 8. These results suggest that NO may directly increase the activity of neuronal persistent Na+ channels, but not transient Na+ channels, through an oxidizing action directly on the channel protein or on a closely associated regulatory protein in the plasma membrane.
Topics: Animals; Cells, Cultured; Dithionitrobenzoic Acid; Dithiothreitol; Hippocampus; Lidocaine; Neurons; Nitric Oxide; Nitroprusside; Patch-Clamp Techniques; Penicillamine; Rats; Rats, Wistar; Sodium Channels; Sodium Cyanide; Tetrodotoxin
PubMed: 10523414
DOI: 10.1111/j.1469-7793.1999.t01-1-00451.x -
Toxicological Sciences : An Official... Sep 2019In adult mouse myocytes, brief exposure to sodium cyanide (CN) in the presence of glucose does not decrease ATP levels, yet produces profound reduction in contractility,...
In adult mouse myocytes, brief exposure to sodium cyanide (CN) in the presence of glucose does not decrease ATP levels, yet produces profound reduction in contractility, intracellular Ca2+ concentration ([Ca2+]i) transient and L-type Ca2+ current (ICa) amplitudes. We analyzed proteomes from myocytes exposed to CN, focusing on ionic currents associated with excitation-contraction coupling. CN induced phosphorylation of α1c subunit of L-type Ca2+ channel and α2 subunit of Na+-K+-ATPase. Methylene blue (MB), a CN antidote that we previously reported to ameliorate CN-induced reduction in contraction, [Ca2+]i transient and ICa amplitudes, was able to reverse this phosphorylation. CN decreased Na+-K+-ATPase current contributed by α2 but not α1 subunit, an effect that was also counteracted by MB. Peptide consensus sequences suggested CN-induced phosphorylation was mediated by protein kinase C epsilon (PKCε). Indeed, CN stimulated PKC kinase activity and induced PKCε membrane translocation, effects that were prevented by MB. Pretreatment with myristoylated PKCε translocation activator or inhibitor peptides mimicked and inhibited the effects of CN on ICa and myocyte contraction, respectively. We conclude that CN activates PKCε, which phosphorylates L-type Ca2+ channel and Na+-K+-ATPase, resulting in depressed cardiac contractility. We hypothesize that this inhibition of ion fluxes represents a novel mechanism by which the cardiomyocyte reduces its ATP demand (decreased ion fluxes and contractility), diminishes ATP turnover and preserves cell viability. However, this cellular protective effect translates into life-threatening cardiogenic shock in vivo, thereby creating a profound disconnect between survival mechanisms at the cardiomyocyte level from those at the level of the whole organism.
PubMed: 31173149
DOI: 10.1093/toxsci/kfz137 -
Memory deficits associated with sublethal cyanide poisoning relative to cyanate toxicity in rodents.Metabolic Brain Disease Mar 2014Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory.... (Comparative Study)
Comparative Study
Food (cassava) linamarin is metabolized into neurotoxicants cyanide and cyanate, metabolites of which we sought to elucidate the differential toxicity effects on memory. Young 6-8 weeks old male rats were treated intraperitoneally with either 2.5 mg/kg body weight (bw) cyanide (NaCN), or 50 mg/kg bw cyanate (NaOCN), or 1 μl/g bw saline, daily for 6 weeks. Short-term and long-term memories were assessed using a radial arm maze (RAM) testing paradigm. Toxic exposures had an influence on short-term working memory with fewer correct arm entries (F(2, 19) = 4.57 p < 0.05), higher working memory errors (WME) (F(2, 19) = 5.09, p < 0.05) and longer RAM navigation time (F(2, 19) = 3.91, p < 0.05) for NaOCN relative to NaCN and saline treatments. The long-term working memory was significantly impaired by cyanide with fewer correct arm entries (F(2, 19) = 7.45, p < 0.01) and increased working memory errors (F(2, 19) = 9.35 p < 0.05) in NaCN relative to NaOCN or vehicle treated animals. Reference memory was not affected by either cyanide or cyanate. Our study findings provide an experimental evidence for the biological plausibility that cassava cyanogens may induce cognition deficits. Differential patterns of memory deficits may reflect the differences in toxicity mechanisms of NaOCN relative to NaCN. Cognition deficits associated with cassava cyanogenesis may reflect a dual toxicity effect of cyanide and cyanate.
Topics: Animals; Cyanates; Disease Models, Animal; Dose-Response Relationship, Drug; Injections, Intraperitoneal; Male; Manihot; Maze Learning; Memory Disorders; Memory, Long-Term; Memory, Short-Term; Plants, Toxic; Rats; Rats, Sprague-Dawley; Sodium Cyanide; Weight Gain
PubMed: 24293006
DOI: 10.1007/s11011-013-9459-2 -
The Journal of Physiology Dec 1985Evoked release of transmitter at the squid giant synapse was examined under conditions where the calcium ion concentration in the presynaptic terminal was manipulated by...
Evoked release of transmitter at the squid giant synapse was examined under conditions where the calcium ion concentration in the presynaptic terminal was manipulated by inhibitors of calcium sequestration. Simultaneous intracellular recordings of presynaptic and post-synaptic resting and action potentials were made during bath application of one of the following metabolic inhibitors: sodium cyanide (NaCN), carbonyl cyanide-p-trifluoromethoxyphenyl hydrazone (FCCP); ruthenium red (RuR) and sodium-free (lithium) sea water. Cyanide and lithium sea water reversibly depressed the post-synaptic potential (p.s.p.) whilst RuR and FCCP blocked the evoked post-synaptic response irreversibly. The progressive reduction of p.s.p. amplitude was accompanied by a reversible increase in synaptic delay. The time course of block of the p.s.p. was similar for different agents and dependent on the rate of presynaptic activity (30-40 min at 0.01 Hz). Recovery of the post-synaptic action potential following block by cyanide and lithium sea water was obtained within 40 min and 5 min respectively. Synaptic depression by the metabolic inhibitors does not result from changes in presynaptic resting or action potentials, nor from a change in post-synaptic receptor sensitivity. The post-synaptic response to the local ionophoresis of L-glutamate was unchanged following inhibition of evoked release of transmitter by cyanide. Injections of EGTA into presynaptic terminals poisoned by cyanide produced transient increases in p.s.p. amplitude, suggesting that cyanide is having its effect through raising intracellular calcium rather than lowering ATP. Control experiments injecting EGTA into unpoisoned nerve terminals showed no apparent effect on evoked transmitter release.
Topics: Action Potentials; Animals; Calcium; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Decapodiformes; Egtazic Acid; Ganglia, Sympathetic; Glutamates; Glutamic Acid; In Vitro Techniques; Lithium; Neurotransmitter Agents; Ruthenium Red; Sodium Cyanide; Synapses; Synaptic Transmission; Time Factors
PubMed: 2419546
DOI: 10.1113/jphysiol.1985.sp015893