Cyanide hypoxia caused

Cyanide toxicity, overshoot hypotension, and myocardial ischaemia. Hypoxia caused by increased ventilation-perfusion mismatch due to pulmonary vasodilatation and inhibition of hypoxic pulmonary vasoconstriction. Rebound hypertension after discontinuation of SNP infusion. 

The nervous system is vulnerable to attack from several directions. Neurons do not divide, and, therefore, death of a neuron always causes a permanent loss of a cell. The brain has a high demand for oxy gen. Lack of oxygen (hypoxia) rapidly causes brain damage. This manifests itself both on neurons and oligodendroglial cells. Anoxic brain damage may result from acute carbon monoxide, cyanide, and hydrogen sulfide poisonings. Carbon monoxide may also be formed in situ in the metabolism of dichloromethylene. 

The toxic effect is known as histotoxic hypoxia. Cyanide also directly stimulates chemoreceptors, causing hyperpnea. Lack of ATP will affect all cells, but heart muscle and brain are particularly susceptible. Therefore, cardiac arrythmias and other changes often occur, resulting in circulatory failure and delayed tissue ischemic anoxia. Death is usually due to respiratory arrest resulting from damage to the CNS, as the nerve cells of the respiratory control center are particularly sensitive to hypoxia. The susceptibility of the brain to pathological damage may reflect the lower concentration of cytochrome oxidase in white matter. 

CO and cyanide have certain similar toxicities, which are a consequence of hypoxia such as disruption of cochlear functions (Tawackoli et al, 2001). CO has been found to cause hearing loss both in humans (Goto et al, 1972 Makishima, 1977 Morris, 1969 Sato, 1966) and in animal... 

Adiponitrile s mechanism of toxicity is similar to cyanide because it can potentially liberate cyanide in the body spontaneously. It forms a stable complex with ferric iron in the cytochrome oxidase enzymes, thereby inhibiting cellular respiration. Cyanide affects primarily the central nervous system (CNS), producing early stimulation followed by depression. It initially stimulates the peripheral chemoreceptors (causing increased respiration) and the carotid bodies (thereby slowing the heart). Early CNS, respiratory, and myocardial depression result in decreased oxygenation of the blood and decreased cardiac output. These effects produce both stagnation and hypoxemic hypoxia in addition to cytotoxic hypoxia from inhibition of mitochondrial cytochrome oxidase. 

Carbon monoxide and methemoglobin-forming agents interfere with oxygen transport, resulting in cellular hypoxia. Cyanide interferes with oxygen use and therefore causes an apparent cellular hypoxia. 

Toxic effects caused by cyanide binding of ferric iron in mitochondrial cytochrome oxidase, affecting cellular ability to utilize 02 in oxidative phosphorylation, causing tissue hypoxia, anaerobic metabolism and lactic acidosis... 

Liesivuori and Savolainen (1991) studied the biochemical mechanisms of toxicity of methanol and formic acid. Formic acid is an inhibitor of the enzyme mitochondrial cytochrome oxidase causing histotoxic hypoxia. It is, however, a weaker inhibitor than cyanide and hydrosulfide anions. The effects of its acidosis are dilation of cerebral vessels, facilitation of the entry of calcium ions into cells, loss of lysosomal latency, and deranged production of ATP, the latter affecting calcium reabsorption in the kidney tubules. Also, urinary acidification from formic acid and its excretion may cause continuous recycling of the acid by the tubular cell Cl-/formate exchanger. Such sequence of events probably causes an accumulation of formate in urine. Other than methanol, methyl ethers, esters, and amides also metabolize forming formic acid. 

Blank et al. (1983) carried ont inhalation toxicity stndies of hydrogen cyanide on Spragne-Dawley rats. Exposnre at 68 ppm HCN in air 6 honrs per day for three consecutive days showed symptoms of hypoactiv-ity, breathing difficnlties, signs of hypoxia, convnlsions, and chromorhinorrhea. Death resulted in three of the five male rats after 1 day of exposure, caused by cyanosis of the extremities, moderate to severe hemorrhage of the lung, and pulmonary edema. All female rats survived. In a 4-week study, no mortality was observed at concentrations up to 58 ppm HCN. A brief exposure to 125 ppm HCN for 15 minutes, however, was fatal to 20% of the test animals. Increased urine thiocyanate levels were observed in test animals However, no adverse effects were observed in rats exposed at 29 ppm HCN 6 hour s weekday in 4-week studies. 

Cyanide causes intracellular hypoxia by inhibiting the intracellular electron transport mechan-... 

One hour of pre-incubation with dihydrolipoic acid (1 iM), but not with a-hpoic acid (1 jiM), reduced damage of neurones from chick embryo telencephalon caused by 1 mM sodium cyanide or iron ions (Muller and Krieglstein 1995). a-Lipoic acid (1 (xM) reduced cyanide-induced neuronal damage when added 24 h before hypoxia, and pre-treatment with a-hpoic acid for >24h enhanced this neuroprotective effect. Both the R- and... 

Figure 3 Effects of various stimuli and mitochondrial inhibitors on the resting membrane potential of quiescent chromaffin cells. A typical example of hypoxia-induced membrane depolarization is shown in (a), using nystatin perforated-patch whole-cell recording. In (b), bicuculline (100 pM), a reversible inhibitor of small-conductance Ca +-dependent K+ channels (SK), also caused membrane depolarization similar to hypoxia. The mitochondrial inhibitors 2,4-drnitrophenol (DNP) and cyanide (CN) did not mimic the h poxia-mduced membrane depolarization seen in (c) and (d), respectively in fact, in (d), CN caused membrane h3q)erpolarization, though in most cases no change in membrane potential was observed. Both DNP and CN were usually without effect even after perfusing the drug for >10 min. In (e), the hyperpolarizing effect of CN was reversed in the presence of 200 pM glibenclamide, a blocker of Katp channels.

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