PHYSIOLOGIC CONSEQUENCES OF CONGENITAL HEART DISEASE 



459 



play a role in the arteriolar changes leading to an 

 increase in pulmonary resistance. It is also possible 

 that the magnitude of the increase in blood flow 

 through the pulmonary vasculature associated with a 

 large defect may be an important factor in the 

 development of an increase in puhnonary vascular 

 resistance. 



Savard and co-workers (208) stated that the 

 increase in blood flow associated with a ventricular 

 septal defect may produce an increase in pulmonary 

 vascular resistance by two mechanisms: /) direct 

 effects of increased pressure and flow on the pul- 

 monary vasculature, and 2) a secondary effect 

 resulting indirectly from the increased work load 

 imposed on the left ventricle. If the work load on the 

 left ventricle is very high, some degree of left ventric- 

 ular incompetence and a consequent increase in 

 left atrial pressure may develop. It is known that in 

 patients with increased left atrial pressure due to 

 left ventricular iaihire or mitral stenosis an elevated 

 pulmonary venous pressure is a stiinulus for the 

 development of an increase in pulmonary vascular 

 resistance (217). Savard and co-workers (208) showed 

 that the left atrial pressure did tend to be increased 

 in the presence of large ventricular septal defects 

 and was significantly decreased after closure of these 

 defects (fig. 25). They concluded that the possibility 

 that an increase in left atrial pressure may be of 

 importance in tlie dc\elopment of the increase in 

 vascular resistance associated with a large ventricular 

 septal defect cannot be ignored. 



It seems unlikely that elevated pulmonary vascular 

 resistance could result solely from a direct effect of 

 increased blood flow on the pulmonary vasculature, 

 since it is uncommon for patients with atrial septal 

 defects to develop pulmonary hypertension in spite 

 of increased pulmonary blood flow which may be 

 very high and is present from childhood into adult 

 life. 



It now is generally recognized that there are two 

 main mechanisms which cause the increase in pul- 

 monary vascular resistance that may occur in patients 

 with left-to-right shunts. The first of these is related 

 to the histologic changes in the small vessels of the 

 lungs — changes that produce obstructive anatomic 

 lesions in the pulmonary vasculature. It is believed 

 that in the neonatal period the normal decline in 

 pulmonary vascular resistance proceeds in normal 

 infants and infants with ventricular septal defect 

 alike (58). When the fall in resistance is marked in 

 infants with large ventricular septal defects, some 

 die in the first few months of life from heart failure 



due to the excessive blood flow through the pulmo- 

 nary artery and consequent heavy work load on the 

 left ventricle. Other infants with defects of similar 

 size apparently respond with a return to a high 

 pulmonary vascular resistance and may survive to 

 lead an active life for many years. It has been sug- 

 gested that in some of these infants there is persistence 

 of the fetal type of pulmonary vasculature. Usually, 

 however, the histologic changes occurring in the 

 pulmonary arterioles are progressive in character. 

 Heath & Edwards (129) described si.x grades of 

 structural changes varying from medial hypertrophy 

 in arteries and arterioles to intimal fibrosis, gener- 

 alized vascular dilatation, appearance of plexiform 

 and angiomatoid lesions, and necrotizing arteritis. 



The second mechanism responsible for the increased 

 pulmonary vascular resistance in this condition is an 

 increase in the vasomotor tone in the small vessels 

 of the lungs. The conclusion that a component of the 

 increase in vascular resistance associated with a 

 ventricular septal defect is due to vasomotor tone is 

 based on the demonstration of the capability of the 

 pulmonary vessels to dilate in such patients. It has 

 been shown in patients with ventricular septal defect 

 that breathing mixtures high in oxygen content may 

 result in a significant decrease in pulmonary-artery 

 pressure and pulmonary vascular resistance, as 

 illustrated in figure 31 (172). Burchell and associates 

 (48) made similar observations in patients with 

 patent ductus arteriosus and pulmonary hypertension. 

 Several groups of workers have also demonstrated 

 that infusion of acetylcholine into the pulmonary 

 artery produces a significant decrea.se in pulmonary 

 vascular resistance (128, 221). 



Since the magnitude and direction of blood flow 

 across a large ventricular septal defect are dependent 

 on the relative resistance to flow in the pulmonary 

 and systemic vascular circuits, it follows that the 

 predominant flow will be in the direction of least 

 resistance. Early in the course of this disease, pul- 

 monary vascular resistance is much lower than sys- 

 temic vascular resistance, resulting in a large flow 

 across the defect in the left-to-right direction. As the 

 lesions in the puhnonary arterioles progress, however, 

 pulmonary vascular resistance increases until the 

 resistances in both circuits are balanced. The flows 

 across the defect then will also be balanced. Even- 

 tually the pulmonary vascular resistance can increase 

 to the point that it exceeds the resistance in the sys- 

 temic vasculature and this results in a predominant 

 shunt in the right-to-left direction. 



Swan and co-workers (240) have studied the effect 



