Calcium hypoxia-ischemia

Tacrolimus capacity to blockade NO pathway is weU demonstrated. NO plays a major role in the pathogenesis of cerebral hypoxia-ischemia injury mediated by glutamate/N-methyl-D-aspartate (NDMA). This injury depends on intracellular calcium influx through NDMA receptor channels, which activate calcineurin with consequent dephosphorylation of constitutive NO synthase (cNOS). Tacrohmus addition to cultured neuronal cells reduced NDMA-mediated toxicity, through the inhibition of calcineurin activation, inhibition of cNOS dephosphorylation and consequent decrease in... 

Mattson, M.P., Zhu, H., Yu, J., and Kindy, M.S., 2000b, Presenilin-1 mutation increases neuronal vulnerability to focal ischemia in vivo and to hypoxia and glucose deprivation in cell culture Involvement of perturbed calcium homeostasis. J. Neurosci. 20 1358-1364. 

Hypoxia is one of the signatures of cyanide poisoning. One of its markers is that ATP declines to about 10% of the normal value. Since ATP forms the substrate for adenylate cyclase, the slow charmels are affected lowering the slow calcium current and depressing the contraction. In CN poisoning, as in ischemia, oxidative metabohsm is blocked and acidosis is enhanced. Acidosis depresses contractility and metabolism while sparing ATP supplies. 

Multinuclear MRS studies in the IPRK with Na, P and Rb (a congener of potassium) MRS have demonstrated that increases in intracellular sodium and decreases in potassium accompany the decrease in ATP induced by hypoxia [331]. Multinuclear studies with F, 1, P and single, double and triple quantum Na MR have also been performed in IPRK by the Gupta group. Brief (10 min) ischemia in an IPRK loaded with the membrane-impermeant intracellular calcium indicator, 5F-BAPTA, caused a partially reversible in-... 

D. V. Fitzpatrick, M. Karmazyn, Comparative effects of calcium channel blocking agents and varying extracellular calcium concentration on hypoxia/reoxygenation and ischemia/reperfusion-induced cardiac injury, J Pharmacol Exp Ther 28, 761-768 (1984). 

It is noteworthy that calcium inhibitory compounds with the ability to inhibit %a+ possess the most potent antiarrhythmic activity against both experimental and clinical arrhythmias (126). For example, nifedipine exerts minimal, if any, antiarrhythmic effect against ischemic induced arrhythmias in intact animals (6, 87, 131). Diltiazem and perhexiline, on the other hand, demonstrate variable antiarrhythmic effects dependent upon their dose and the mechanism responsible for arrhythmia production (ischemia, hypoxia, digitalis, aconitine) (102, 126, 151, 152). Only verapamil, which has been investigated in the largest number of experimental and clinical trials, has demonstrated consistent antiarrhythmic activity against cardiac arrhythmias regardless of cause (155) ... 

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