Children born with cyanotic congenital heart disease (transposition of the great arteries, tetralogy of Fallot) are known to develop potentially lethal dysrhythmias. Since these atrial and ventricular dysrhythmias may be result of chronic hypoxia, the aim of this proposal is to delineate the degree to which chronic hypoxia predisposes the newborn and developing animal to these dysrhythmias. We will determine the effect of chronic hypoxia on: (1) the electrophysiological responsiveness of isolated cardiac tissue (S-A node, atrial and ventricular myocardium, and ventricular Purkinje fibers) to muscarinic and beta-adrenergic stimulation; (2) cardiac muscarinic receptor and beta-adrenoreceptor concentration and binding characteristic; and (3) reflex autonomic control fo cardiac rate and refractoriness. By using this three level approach (whole animal, isolated tissue, membrane receptor), the study will test the hypothesis that: chronic hypoxia during post-natal development results in changes in the cardiac action potential and the autonomic control of cardiac electrical function, thereby causing a predisposition to dysrhythmias.
| Posner, P; Baker, S P; Epstein, M L et al. (1991) Effects of chronic hypoxia during maturation on the negative chronotropic effect of [H+] on the rabbit sino-atrial node. Biol Neonate 59:109-13 |
| Baker, S P; Buss, D D; Epstein, M L et al. (1989) Effect of chronic hypoxia on cardiac beta-adrenergic and muscarinic receptors during maturation. Res Commun Chem Pathol Pharmacol 63:307-15 |
