Factors controlling pulmonary vascular resistance in fetal lambs

doi:10.1016/S0022-3476(65)80426-7

The Journal of Pediatrics

Volume 67, Issue 4, October 1965, Pages 568-577

https://doi.org/10.1016/S0022-3476(65)80426-7 Get rights and content

A series of experiments measuring pulmonary vascular resistance in the fetal lamb revealed that spontaneous changes in resistance occur in the unexpanded fetal lung; expansion of the fetal lung with a gas mixture that produces no significant alteration in arterial pO₂ or pCO₂ results in a marked fall in pulmonary vascular resistance; expansion of fetal lungs with deoxygenated dextran in saline produces only a small fall in pulmonary vascular resistance; inflation of fetal lungs with oxygenated dextran in saline and arterial blood produces a marked fall in vascular resistance; the fall in pulmonary vascular resistance with air inflation of the fetal lung cannot be ablated by vagotomy, atropinization, or administration of ismeline.

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The preterm infant, defined as birth before 37 weeks gestation, provides unique medical and surgical challenges to health care providers due to a myriad of anatomical underdevelopments and physiologic derangements. The physiology of prematurity as it relates to anesthesia is of particular importance when preparing for surgery. Anatomic differences of the premature airway and altered respiratory mechanics, such as a smaller airway diameter, increased oxygen consumption, bronchopulmonary dysplasia and apnea place these infants at risk for rapid and profound desaturation and hypoventilation during anesthesia. The immature heart has not had time to develop sufficient muscle fibers for optimal contractility. In addition, persistent pulmonary hypertension of the newborn may develop when right-to-left shunting of blood occurs through a patent ductus arteriosus and/or a patent foramen ovale due to failure of the pulmonary vascular resistance to drop at birth. These factors may combine and lead to significant cardiovascular collapse during surgery. Premature infants are susceptible to metabolic derangements such as hypoglycemia and hypocalcemia due to improper storage and loss of maternal-fetal transfer during gestation. The liver and kidneys are underdeveloped, leading to altered drug metabolism, thus, anesthetic drugs must be tailored accordingly. Neonatal surgical emergencies, such as congenital diaphragmatic hernia, hypertrophic pyloric stenosis, necrotizing enterocolitis and gastroschisis, can present at any time and be life-threatening. Immediate surgical intervention is not always necessary and there is often time for medical optimization. Advances in neonatal care have improved the morbidity and mortality of critically ill newborns.
The Extremely Premature Infant (Micropremie) and Common Neonatal Emergencies
2018, A Practice of Anesthesia for Infants and Children
The preterm infant, defined as birth before 37 weeks gestation, provides unique medical and surgical challenges to health care providers due to a myriad of anatomical underdevelopments and physiologic derangements. The physiology of prematurity as it relates to anesthesia is of particular importance when preparing for surgery. Anatomic differences of the premature airway and altered respiratory mechanics, such as a smaller airway diameter, increased oxygen consumption, bronchopulmonary dysplasia and apnea place these infants at risk for rapid and profound desaturation and hypoventilation during anesthesia. The immature heart has not had time to develop sufficient muscle fibers for optimal contractility. In addition, persistent pulmonary hypertension of the newborn may develop when right-to-left shunting of blood occurs through a patent ductus arteriosus and/or a patent foramen ovale due to failure of the pulmonary vascular resistance to drop at birth. These factors may combine and lead to significant cardiovascular collapse during surgery. Premature infants are susceptible to metabolic derangements such as hypoglycemia and hypocalcemia due to improper storage and loss of maternal-fetal transfer during gestation. The liver and kidneys are underdeveloped, leading to altered drug metabolism, thus, anesthetic drugs must be tailored accordingly. Neonatal surgical emergencies, such as congenital diaphragmatic hernia, hypertrophic pyloric stenosis, necrotizing enterocolitis and gastroschisis, can present at any time and be life-threatening. Immediate surgical intervention is not always necessary and there is often time for medical optimization. Advances in neonatal care have improved the morbidity and mortality of critically ill newborns.
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Citation Excerpt :
Using a radio-opaque substance administered through an IV-line and X-ray imaging he visualized that as soon as the lungs were recruited pulmonary blood flow increased [23]. However, experimental studies using a lamb model which was infused with marked spheres before birth [24,25] have shown that pulmonary vasodilation actually occurs in response to lung aeration, leading to a gradual reduction in pulmonary arterial pressure. This was confirmed by more recent research using a rabbit pup model and phase contrast X-ray imaging simultaneously with angiography and in lambs using flow probes around the pulmonary artery [8,26].
The neonatal transition during birth is characterized by major physiological changes in respiratory and hemodynamic function, which are predominantly initiated by labor, lung aeration and clamping of the umbilical cord. Lung liquid clearance and lung aeration are not only important for the establishment of functional residual capacity, but these events also trigger the significant decrease in pulmonary vascular resistance and increase in pulmonary blood flow. Clamping the umbilical cord also contributes to these hemodynamic changes by increasing the systemic vascular resistance and sudden loss of a large proportion of venous return. This results in blood flow changes both through the foramen ovale and ductus arteriosus and eventually leads to closure of these structures and the separation of the pulmonary and systemic circulations. Most of the early theories describing neonatal transition are based on imaging studies of human infants from the 1900s. Some of these theories have been disproven in more recent studies using more accurate and non-invasive imaging techniques. This review will provide an overview of the theories suggested to explain the process of liquid clearance and lung recruitment and also addresses new findings in this field of research.
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^**: Supported by Research Grants HD-00250-02 of the National Institute of Child Health and Human Development and HE-04392 of the National Heart Institute, United States Public Health Service.

^*: Address, University of Kansas Medical Center, 39th and Rainbow Blvd., Kansas City, Kan. 66103.

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Factors controlling pulmonary vascular resistance in fetal lambs**

The nervous control of the pulmonary circulation

Arch. exper. Path. u. Pharmakol.

Pulmonary vascular responses to short term hypoxia in human subjects

Circulation

Pulmonary vasomotor responses of isolated perfused cat lungs to anoxia and hypercapnia

Quart. J. Exper. Physiol.

Respiratory gases in the regulation of pulmonary circulation

Physiol. Rev.

The foetal circulation in the lamb

J. Physiol.

The effect of ventilation of the foetal lungs upon the pulmonary circulation

J. Physiol.