Congenital Heart Disease and Other Malformations Produced by Influenza A Virus and Allantoic Fluid in the Chick Embryo

Abstract

The effect of both active and heat-inactivated influenza A virus, chick allantoic fluid, and of buffered saline solution on the mortality and appearance of congenital malformations in the white Leghorn chick embryo, especially in the heart, was studied. Active influenza A virus produced a high mortality rate during the initial stages of development, when formation of the cardiac septa had barely begun and the primordia of the valves were yet to appear. Consequently, no congenital heart disease was found in the group inoculated with active virus, though profound alterations of the nervous system, sensorial organs and general body shape were observed. The effects of allantoic fluid with and without heat-inactivated virus were the same high incidence of congenital valvular disease (pulmonary stenosis, thickening of the mitral valve), and interventricular septal defect. Inoculation of buffered saline solution produced an increased mortality rate and structural malformations outside the heart, but had no effect on the development of the heart. Possible mechanisms of action of these terato-genic agents are discussed.

Validating the Paradigm That Biomechanical Forces Regulate Embryonic Cardiovascular Morphogenesis and Are Fundamental in the Etiology of Congenital Heart Disease

“…The embryonic heart has been the subject of intense investigation for over a century. Initially, the chick embryo was the focus for academic investigation due to the opportunity to characterize morphogenesis via careful serial sections and histology [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 ] the opportunity to isolate and investigate myocardial electromechanical maturation [ 9 , 10 , 11 ], the ability to directly observe via light microscopy [ 12 , 13 , 14 , 15 , 16 ], instrument [ 17 , 18 , 19 , 20 , 21 , 22 , 23 ] and measure normal cardiac function using fluid-filled pipettes [ 24 , 25 , 26 ], and the interest of investigators to explore the consequences of increased and decreased ventricular loading conditions on cardiovascular (CV) morphogenesis [ 27 , 28 , 29 ]. The key findings of these studies included the progressive electrophysiologic maturation of the developing myocardium, the ability of the heart to generate phasic pressure and pulsatile blood flow in the absence of mature cardiac valves, including the contribution of the contracting conotruncus (CT) in the early embryo [ 21 ] and the impact of altered intracardiac blood flow on ventricular and vascular morphogenesis.…”