title: Developmental factors contributing to the susceptibility to bradycardia in isolated, cultured fetal mouse hearts.
abstract: A propensity for bradycardia in preterm human infants suggested that the heart rate response to cholinergic stimulation may vary during development. Isolated, intact fetal mouse hearts (FMH) in organ culture were used as a model to explore developmental differences in chronotropic response to cholinergic stimulation. FMH's of gestational ages (GA) from 13-22 days, maintained for 36 hr in culture, were exposed to acetylcholine (AcH) with and without prior addition of physostigmine. Heart rate decreased markedly with 10(-4) and 10(-6) M AcH (84 +/- 3 and 48 +/- 4%) in 13-14 day hearts, but the decrease was progressively blunted with increasing age and was only 7 +/- 3 and 3 +/- 2% at 21-22 days GA. Physostigmine markedly enhanced the cholinergic response in older hearts with 54 +/- 4 and 32 +/- 5% decreases in heart rate with the two doses of AcH at 21-22 days. However, it did not alter the response in younger hearts. The data suggest that the chronotropic response to AcH progressively diminishes with advancing GA and the extent of intrinsic cholinesterase activity at different GA's is, in part, responsible for the decrease.
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D001919:Bradycardia / Q000209:etiology; D005318:Fetal Heart / Q000187:drug effects* / Q000503:physiopathology; D005865:Gestational Age; D006339:Heart Rate / Q000187:drug effects*; D007545:Isoproterenol / Q000494:pharmacology; D051379:Mice; D009924:Organ Culture Techniques; D010830:Physostigmine / Q000494:pharmacology
chemical_list: D010830:Physostigmine; D007545:Isoproterenol; D000109:Acetylcholine