Experiments on cardiomyocytes are quantified by electrophysiological measurements and the risk of arrhythmia by its incidence/unit time in a population. Our aim is to estimate the risks of arrhythmia using measurements from myocytes, with exposure to Carbon monoxide (CO) as an example. Recordings were from iCell cardiomyocyte, during 10mins exposure to CO Releasing Molecule CORM-2. Computations used O'Hara-Rudy (ORd) human cardiomyocyte models, with mean parameters modified for sex, CO exposure, and variability by Gaussian distributed conductances.
CO exposure produces APD90 prolongation, early afterdepolarizations, oscillatory plateau and failure to repolarize. Voltage clamp experiments show CO changes the ionic conductances. Incorporation of these changes into standard ORd sub-epicardial cells and modified for women shows that for 300s of periodic pacing at 1/s: APD prolongation by 56% (men) and 34% (women), intra-epicardial APD dispersion by 133%, 82%, and in one-dimensional homogenous epicardial excitable tissue-model -20.5% changes in propagation velocity; and -12.7%, -2.6% in temporal vulnerable window, and -30.6%, -22.6 changes in spatial vulnerable window. The epicardial cell restitution curve shows prolongation of cell APD at all cycle lengths. Increases in APD prolongation, dispersion, temporal and spatial vulnerable window and decreases in propagation velocity are all pro-arrhythmogenic indices with units of ms, mm, cm/s, and can be remapped as measures of changes in the probabilities of the occurrence of pro-arrhythmogenic trigger events and changes in the probabilities that the medium is susceptible to, and can maintain, a re-entrant arrhythmia. Cell probabilities act as triggers and summate; and interact multiplicatively with the tissue probabilities to give the change in the probability of onset of an arrhythmic episode. CO induced changes in cardiomyocyte electrophysiology are predicted to approximately double the risk of ventricular arrhythmia.