Early postnatal cardiovascular maladaptation and peri-intraventricular hemorrhage in extremely preterm infants

2016-04-21Peri-intraventricular hemorrhage (P/IVH) is a devastating type of brain injury that affects up to a third of the very preterm infants during the early postnatal transition, the first few days after birth. This complication of prematurity is a major risk factor for long-term morbidities and mortality among this vulnerable population. ❧ Cardiovascular maladaptation during the transition from fetal to neonatal life may predispose these patients to P/IVH. There are inherent vulnerabilities of the premature cardiovascular system (CVS). For example, the immature myocardium has a limited capacity to compensate for an increase in afterload. This is particularly important during the transition from fetal to neonatal circulation. Right at birth, removal of low resistance placental circulation increases the systemic vascular resistance (SVR) leading to an increase in left ventricular afterload. This is thought to prevent the normal rise in left ventricular output resulting in low systemic blood flow. In addition to the inherent vulnerabilities of the immature CVS, interventions aimed at supporting the preterm infant and reducing injury to particular organ may predispose the infant to injury of the other organs. Among such interventions, permissive hypercapnia is commonly implemented strategy to reduce the need for respiratory support and thereby decrease lung injury from mechanical ventilation. However, permissive hypercapnia results in respiratory acidosis. In the setting of delayed and prematurity-related inadequate renal compensation, respiratory acidosis leads to a significantly lower than normal pH during the transitional period. In older children and adults, low pH markedly alters the hemodynamics. Both myocardial contractility and SVR decrease while the cardiac output may increase. Interestingly, animal studies indicate that the response of neonatal CVS to low pH is different than more mature heart. Unfortunately, despite the common practice of permissive hypercapnia, little is known about the effect of acidic pH on CVS in premature infants. In chapter 2, the cardiovascular effects of acidosis in premature infants during early transitional period and posttransition in the first 2 weeks after birth are explored. ❧ Pathogenesis of P/IVH is complex and likely several mechanisms are in play. Cerebral ischemia and reperfusion is thought to be an important mechanism of development of P/IVH. However, the temporal relationship between ischemic and reperfusion phases and occurrence of P/IVH is unknown. Furthermore, the underlying causes of ischemia and reperfusion phases of injury remain speculative. As mentioned earlier, some have hypothesized that postnatal increase in afterload leads to low cardiac output which in turn could cause cerebral hypoperfusion. Permissive hypercapnia has also been implicated in pathogenesis of P/IVH likely via attenuation of cerebral blood flow autoregulation and potentiation of reperfusion phase of injury. Chapter 3 will explore the temporal relationship between changes in indices of CBF and occurrence of P/IVH. In addition, the role of postnatal cardiovascular maladaptation in pathogenesis of P/IVH is discussed