Maturation of Responsiveness to Cardioactive Drugs

Wildenthal, K.

doi:10.1172/jci107411

Cited by 43 publications

(14 citation statements)

References 24 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This mechanism might explain the similar AcH responses noted in previous studies using fetal mouse hearts (37,45). However, pharmacologic release of intrinsic AcH in the chick or fetal mouse heart has not been conclusively demonstrated.…”

Section: Discussionmentioning

confidence: 67%

“…However, the apparently exaggerated responsiveness to AcH noted in the least mature hearts in the present investigation is more difficult to explain. Indeed, other investigators using the mouse (37,45) as well as other species (12,32,36) suggest that AcH response becomes progressively greater with increasing GA and increasing parasympathetic innervation. Variability in species, developmental age, specific methodology of preparation and preservation of fetal hearts, AcH dose, and experimental design make comparisons of AcH dose response relationships difticult.…”

Section: Discussionmentioning

confidence: 95%

“…Previous studies demonstrating greater responsiveness with increasing parasympathetic innervation have generally related such a pattern to the gradual accruance of AcH receptor sites (37,39) and/or increasing receptor-response sensitivity (31,33,45). Certainly receptor site density, sensitivity and affinity for neurotransmitters along with several other components of neuroeffector physiology may undergo developmental change and, thus, explain different age-related dose responses.…”

Section: Discussionmentioning

confidence: 98%

“…The marked bradycardia induced in the youngest hearts (14-15 days GA) is especially remarkable in that cardiac parasympathetic innervation i~-~r e s u m a b l~ either not present or is jusi beginning at this age (30,45).…”

Section: Discussionmentioning

confidence: 99%

“…must imply functional muscurinic acetylcholine receptors and an operative, chronotropic receptor-response coupling. Investigations of chronotropic responsiveness in hearts from fetal rats, (12,36) chicks, (6,14) mice (45) and humans (42) have demonstrated AcH induced heart rate slowing before morphologic parasympathetic innervation. Furthermore, Roeske and Yamanura (37) and Sastre et al (39) have detected AcH receptors before innkrvation by labeled competitive antagonist binding.…”

Section: Discussionmentioning

confidence: 99%

See 4 more Smart Citations

Developmental Factors Contributing to the Susceptibility to Bradycardia in Isolated, Cultured Fetal Mouse Hearts

Maurer

1979

Pediatr Res

View full text Add to dashboard Cite

Summarvtle and attention behavioral responses (3,21,34,35,42). 2) The A propensity for bradycardia in preterm human infants suggested that the heart rate response to cholinergic stimulation may ;ary 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 lo-' and lo-' 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 f 2 % at 21-22 days GA. Physostigmine markedly enhanced the cholinergic response in older hearts with 54 f 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 i n 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. SpeculationIncreasing cholinesterase activity during gestation may, in part, protect more mature fetal hearts from severe bradycardia. Likekise, "unprotected" AcH receptors may account for the pronounced bradvcardia in less mature hearts. If unprotected AcH receptors are important to the bradycardic response, does this play any role in vivo? One possibility is that the fetal heart's capacity to synthesize AcH and acetylcholinesterase may not develop synchronously. Such nonparallel enzyme system develop ment might occur as a normal developmental sequence, exposed abnormally by premature birth or conversely, may be induced by abnormalities during gestation ( e.g., chronic hypoxemia, intrauterine malnutrition). This general scheme is not unprecedented in that asynchronous development of interrelated enzymes systems deleterious to the prematurely born have already been well documented in the liver and lung. This hypothesis is currently being investigated.The widespread use of heart rate monitoring in fetal and neonatal intensive care has revealed a rather high incidence of bradyarrhythmias in the newborn infant (8,21,25,38,41,42). In fact, detection of bradycardia has become a major factor in determining the therapeutic threshold of certain fetal and neonatal afflictions (13,17).Clinical and laboratory investigations as well as simple clinical observations have suggested: 1) Bradycardia (usually sinus) occurs spontaneously and.in response to a wide variety of stimuli such as increased CNS pressure, umbilical cord compression, hypoxemia, apnea, nasopharyngeal and laryngeal stimulation, defecation, star-incidence and/or the severity ofbradycardia may be increased in the premature infant (18,26,27,34).As a group, immature fetuses and neonates are certainly subject to more bradycardia-evoking stimuli. However, the occurrence and severity of this ...

show abstract

Section: Discussionmentioning

confidence: 67%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Developmental Factors Contributing to the Susceptibility to Bradycardia in Isolated, Cultured Fetal Mouse Hearts

Maurer

1979

Pediatr Res

View full text Add to dashboard Cite

show abstract

Acetylcholinesterase in prenatal rat heart: A marker for the early development of the cardiac conductive tissue?

et al. 1987

View full text Add to dashboard Cite

In rat embryos, acetylcholinesterase (AChE, EC 3.1.1.7) activity is present in a continuous sleeve of myocytes that extends from the myocardium that is adjacent to the atrioventricular endocardial cushions via the ventricular trabeculae to the outflow tract. No activity is found in the atrial roof, in the ventricular walls and in the interventricular septum except for its subendocardial surface. AChE-positive cells are first identified in 11-day rat embryos, while the prototypical distribution is best demonstrable in 13-day embryos. Part of the AChE-positive cell system is identifiable as a precursor of the adult conduction system by topographical criteria in 16-day fetuses and by morphological criteria in 20-day fetuses. At birth (2 days later), AChE activity has disappeared from the cardiac myocytes except for a ring of tissue at the atrial side of the atrioventricular junction. These findings suggest that the embryonic heart can be divided into an upstream myocardium that has no AChE activity and a downstream myocardium that is characterized by the presence of AChE. Furthermore they suggest that an acetylcholine-dependent mechanism may be responsible for the retardation of the depolarization wave in the downstream parts of the heart. Finally they show that the adult conduction system is formed by a transdifferentiation of part of a far more extensive embryonic precursor system.

show abstract

Chronotropic and Cyclic Adenosine Monophosphate Response of Fetal Rat Heart in Organ Culture to Isoproterenol, Quinidine, and a Dysrhythmogenic Agent

Eyer

Johnson

1977

Journal of Pharmaceutical Sciences

View full text Add to dashboard Cite

Maturation of Responsiveness to Cardioactive Drugs

Cited by 43 publications

References 24 publications

Developmental Factors Contributing to the Susceptibility to Bradycardia in Isolated, Cultured Fetal Mouse Hearts

Developmental Factors Contributing to the Susceptibility to Bradycardia in Isolated, Cultured Fetal Mouse Hearts

Acetylcholinesterase in prenatal rat heart: A marker for the early development of the cardiac conductive tissue?

Chronotropic and Cyclic Adenosine Monophosphate Response of Fetal Rat Heart in Organ Culture to Isoproterenol, Quinidine, and a Dysrhythmogenic Agent

Contact Info

Product

Resources

About