A New Perspective for Identifying Potential Cardiac Sensitizers
Rept. for Oct 98-Oct 99
NAVAL HEALTH RESEARCH CENTER WRIGHT-PATTERSON AFB OH TOXICOLOGY DETACHMENT
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Cardiac sensitization is the sensitization of the heart to circulating catecholamines after exposure to an exogenous chemical, such that sudden alarm or exercise may precipitate a cardiac arrest. The purpose of this investigation is to develop a predictive mathematical model that can identify cardiac sensitizers. The dog and the swine were used as surrogates for the human. Physiologic and electrocardiographic measurements were taken during the control period and after each dose of ouabain, a digitalis glycoside known to provoke ventricular arrhythmia. Logistic regression was used to develop the model by converting binary data into a function curveequation that can estimate of the probability of a particular result, in this case experiencing a cardiac arrhythmia. Five parameters were significant predictors of arrhythmia in dog HR, PQ, QT, Paos and dPdtsub max, and three were significant in the swine PQ, QT and dPdtsub max. The study demonstrates that several mathematical models can be constructed to predict the onset of ouabain induced arrhythmia, in both the dog and the swine, and that there are similarities in the two animal models. Efforts to reduce the number of parameters to a single term showed colinearity among simple pair wise combinations. Since the QT interval was significant in both species, it appears to be the most promising of all the parameters for predicting cardiac sensitization.
- Medicine and Medical Research
- Stress Physiology