Effects of Lung Distension and Spontaneous Fetal Breathing on Hemodynamics in Sheep

Abstract

ABSTRACT. In previous studies, we determined that pul-been shown to have independent effects on blood flow, neural monary ventilation and oxygenation were largely respon-reflexes, and hormone responses in proportion to the inflation sible for increasing pulmonary blood flow and for altering pressures achieved (5, 6), the possibility exists that some of the central blood flow patterns but could not account for the responses observed previously were a consequence of positive increase in combined ventricular output (the sum of left pressure ventilation per se, and not related to normal breathing and right ventricular outputs) that usually occurs after activity initiated at birth. birth. We had ventilated fetuses with oscillating positive Recent studies have demonstrated that spontaneous negative pressures; the possibility that high intrathoracic pressures pressure pulmonary ventilation can be initiated and maintained adversely affected cardiac output could not be ruled out. in fetal sheep when the umbilical cord is occluded while oxygen To determine the effects of negative intrathoracic pressure is introduced into the fetal trachea (7-10). We applied this ventilation, we occluded the umbilical cord of nine long-technique to determine the effects of spontaneous, rhythmic term instrumented fetal sheep at 135 f 1.2 d gestation pulmonary ventilation on blood flow patterns at birth. We while introducing humidified oxygen gas intratracheally. measured combined ventricular output, the sum of left and right This stimulated continuous fetal respiratory activity, which ventricular outputs, and peripheral blood flow distribution in a resulted in negative intrathoracic pressures and increased group of fetal sheep in utero to determine the effects of spontafetal oxygenation. Pulmonary blood flow increased from neous negative pressure ventilation on hemodynamics at birth.121 + 60 to 901 + 139 mL.min.-'.I00 g-' (mean + SD) and descending aortic blood pressure increased from 7.0 f MATERIALS AND METHODS 1.2 to 9.6 + 2.0 kPa. Central blood flow patterns were altered so that right to left shunting of blood through the Animals and Surgical Preparation. All procedures complied foramen ovale and ductus arteriosus was abolished and a with NIH guidelines and were approved by the Committee left to right shunt developed across the ductus arteriosus. on Animal Research at UCSF. We studied nine fetal sheep at However, cardiac output did not increase significantly. This 135 f 1.2 d gestational age (range 133-1 37 d; term is 145 d). may be related, in part, to the increase in afterload. It is Food, but not water, was withheld from the ewe for 24-36 h clear that pulmonary ventilation and oxygenation are the before surgery. After local anesthesia (2% lidocaine hydrochlomajor factors responsible for changing pulmonary blood ride), low spinal or epidural anesthesia was achieved with 4 mL flow and central blood flow patterns at birth. Other birth-of 1 % tetracaine hydrochloride (Pontocaine HCI, Breon Laborelated events, such as a decrease in environ...

Ventilation of the Very Immature Lung In Utero Induces Injury and BPD-Like Changes in Lung Structure in Fetal Sheep

“…These experiments were short in duration, the umbilical cord was obstructed and the lungs were not examined for VILI (7)(8)(9). We chose to perform IUV in fetal sheep at 110 d when the distal air-spaces have few alveoli, are mostly comprised of saccules and the epithelial cells are mainly undifferentiated (15), because this structure resembles a human lung at ϳ26 wk gestation.…”

“…Previously in utero ventilation (IUV) was used to study birth-related changes in cardiopulmonary physiology in late gestation, but not VILI (7)(8)(9). IUV has numerous advantages as a model for VILI as the fetus remains on placental support and is not dependent upon ventilation for gas exchange.…”

Influence of Fetal Breathing Movements on Pulmonary Hemodynamics in Fetal Sheep

“…During fetal life, the majority (88%) of right ventricular output bypasses the lungs and is shunted into the systemic circulation via the ductus arteriosus (1). In the late-gestation fetus, the relatively high PVR has been attributed to the low PO 2 of blood perfusing the lungs (2,3), to the balance between vasoconstrictor and vasodilator activity (4 -7), and to the high level of resting lung expansion in the fetus (8).…”

Bronchial epithelium-associated pulmonary arterial muscle relaxation in the rat is absent in the fetus and suppressed by postnatal hypoxia

“…Pulmonary vascular adaptation following birth is associated with alveolar expansion, pulmonary vasodilatation, and flow of the total cardiac output through the lungs, thus allowing for adequate gas exchange (9). Matching of perfusion to ventilation in the lung is acutely controlled by the hypoxic pulmonary vasoconstriction response (7).…”