ECGs and Metabolic Networks: An in silko Exploration of Cyanide-caused Cardiac Toxicity

摘要

The primary effect of cyanide (CN) on cardiac tissue is the interference with the cellular energy balance, that is, inhibition of the mitochondrial enzyme cytochrome oxidase preventing the transfer of electrons from cytochrome c to molecular oxygen. The impacted aerobic metabolism results in lactic acid acidosis and reduced adenosine triphosphate (ATP) concentration leading to anoxia. In tandem, with a reduction in cellular energy, a change in the calcium ion concentrations in several cellular compartments, calcium current modulation and an inotropic effect develops, Way (1984). Simultaneously, a gradual decrease in action potential duration is noted. The subsidiary cellular processes are still being elucidated, but the sine-non-quo for the development of effective therapeutic regimes is management of these effects. An in silico approach is presented in this paper showing how available data and models can be used in the development of new therapies.