Neural Crest Ablation Versus Sham Surgical Effects in a Chick Embryo Model of Defective Cardiovascular Development

Abstract

ABSTRACT. In chick embryos, ablation of premigratory neural crest destined for the third, fourth, and sixth pharyngeal arches results in persistent truncus arteriosus and interrupted aortic arch. Studies of cardiogenesis in these embryos have shown decreased ejection fraction and ventricular dilation with normal cardiac output. The experimental embryos that survive to d 11 of incubation have a higher cardiac output than nonsurvivors at the same earlier stage of development. We hypothesize that this survival is due to a surgically induced decrease in vascular resistance of the embryonic and vitelline vessels. Embryos from 15 opened eggs, eight sham-operated embryos, and 13 neural crest-ablated embryos were examined at stage 18. The sham-operated embryos were treated identically with the experimental embryos except that neural crest was not ablated. Ejection fraction and cardiac output were determined by cinephotography. Mean dorsal aortic and diastolic ventricular (approximates mean atrial) pressures were determined by a servo-null pressure technique and used to calculate vascular resistance. The experimental embryos had a significantly decreased ejection fraction in comparison with either sham-operated embryos or embryos from eggs that remained unopened until just before cinephotography. The experimental and sham-operated embryos had a higher cardiac output than embryos from unopened eggs. The calculated vascular resistance was also significantly lower in both the experimental and shamoperated embryos than in the embryos from unopened eggs. Neural crest ablation appears to cause a decreased ejection fraction. Sham surgery is associated with a higher cardiac output and lower vascular resistance. These hemodynamic changes may be related to opening and resealing the eggshell, which would interfere with oxygen delivery and water vapor exchange. (Pediatr Res 33: 628-631,1993)The neural crest has been shown to be very important in normal cardiovascular development (1). The region of neural crest contributing to cardiovascular development extends from the midotic placode to the caudal limit of somite three. Cells from this region migrate from the neural fold into pharyngeal arches three, four, and six (2-4). A population of the neural crest-derived cells continue their migration through the pharyngeal region into the outflow tract of the heart, where they participate in outflow septation. Ablation of the premigratory neural crest destined for the third, fourth, and sixth pharyngeal Received August 11, 1992; accepted January 22, 1993. Correspondence and reprint requests: Linda Leatherbury, M.D., Pediatric Cardiology, BAA8302, Medical College of Georgia, Augusta, GA 309 12-37 10.Supported by PHs Grant HL-36059.arches and outflow septa produces a high incidence of persistent truncus arteriosus and anomalous development of the derivatives of the aortic arch arteries. Nishibatake el al. ( 5 ) demonstrated that ablation of premigratory neural crest destined for pharyngeal arches four and six resulted in a 73% incidence of pe...

Noninvasive phenotypic analysis of cardiovascular structure and function in fetal mice using ultrasound

“…Our M‐mode measurements provided a fractional shortening of 58%. This is higher than in humans (30%), but is similar to that seen in chick embryos (69%) (Leatherbury et al, 1993). We also assessed contractility using the Tei index as described by Tei et al (1995).…”

Developmental spectrum of cardiac outflow tract anomalies encompassing transposition of the great arteries and dextroposition of the aorta: Pathogenic effect of extrinsic retinoic acid in the mouse embryo

“…Kirby et al (1990) inferred that aortic arch anomalies, caused by the decrease in the cardiac neural crest, altered blood flow characteristics, leading to abnormal morphogenesis in the proximal outflow tract via an upstream hemodynamic effect. Hemodynamic measurements of the neural crest‐ablated chick embryos (Tomita et al, 1991; Leatherburry et al, 1991, 1993) or Splotch mice (Conway et al, 1997b) revealed changes in hemodynamic or electrophysiological parameters. However, a direct relation between such physiological changes and morphogenesis has not been demonstrated.…”

Connecting teratogen‐induced congenital heart defects to neural crest cells and their effect on cardiac function

“…A surprising finding was that removal of CNCCs had an impact on early cardiac function (stage 14–16) 24–28 hr before the CNCCs derivatives begin to enter the outflow tract (stage 25 in chicken embryos) (Leatherbury et al, , 1991, ; Tomita et al, ; Farrell et al, ). Cardiac contractility was depressed with reduced shortening fraction and ejection fraction, at stage 18 (68–72 hr or 3 days of incubation).…”

“…A surprising finding was that removal of CNCCs had an impact on early cardiac function (stage 14-16) 24-28 hr before the CNCCs derivatives begin to enter the outflow tract (stage 25 in chicken embryos) (Leatherbury et al, 1990b(Leatherbury et al, , 1993Tomita et al, 1991;Farrell et al, 2001).…”