The Effects of 8-Azaguanine on Cardiac Development in the Chick Embryo

Abstract

The etiology of congenital heart lesions is varied and multifactorial hypothesis has gained wide acceptance. Regardless of the etiologic agent, the offending factor must act through a common pathway by either changing the growth rate, the resorptive process or the molding mechanical effect of the circulating blood. In search of a model for producing congenital heart disease in a reproducible fashion we used 8-azaguanine (a purine analogue) to study the effects of growth inhibition on developing chick embryo hearts. One half ml of 8-azaguanine (25mg% solution) was injected into the yolk sac of fertile white Leghorn eggs at 23rd stage. Eggs injected with 1/2ml of normal saline served as control. Eight-azaguanine-treated eggs delivered less normal embryos (29/188) than the saline-injected eggs (119/158, p<0.001) and more dead embryos (106/188 vs 0/158 respectively, p<0.001). Serial sections of the hearts extracted at 35th stage in the 8-azaguanine-treated (64 specimens) and control group (96 specimens) revealed no congenital heart defect in the latter group, whereas the development of the hearts were halted either in the tubular stage (12/64, p<0.01) or in the primitive stages of development (28/64, p<0.001). The thickness of the ventricular myocardium was also greatly reduced.It is concluded that: 1) Certain types of congenital heart defects such as endocardial cushion defect, and common ventricle could be reproducibly produced by growth inhibiting agent 8-azaguanine in the chick embryo. 2) Experimental models for production of congenital heart defects through acceleration of the growth or changing the rate of tissue resorption must be sought.