Chronic Hypoxemia in the Newborn Lamb: Cardiovascular, Hematopoietic, and Growth Adaptations

Abstract

ABSTRAm. We have created a model of chronic hypoxemia in the newborn lamb by decreasing pulmonary blood flow in the presence of an atrial septal defect. Via a left lateral thoracotomy, we place an inflatable balloon around the pulmonary artery and perform an atrial septostomy under direct vision. We also insert several vascular catheters and place an electromagnetic flow transducer around the ascending aorta. Three days after surgery, we inflated the balloon in 11 lambs such that arterial oxygen saturation decreased to 60 to 75%. Studies were performed on these lambs twice weekly and weekly on 12 normoxemic lambs. Growth decreased sharply (47 2 123 versus 221 f 82 g/ day) at the onset of hypoxemia and remained low, although oxygen consumption followed the normal gradual decline. Heart rate remained elevated throughout the study. Arterial Pcoz levels decreased from 40 + 5 to 35 f 7 torr and remained low. Systemic blood flow decreased at balloon inflation but quickly returned to normal. Mixed venous saturation was low, but could decrease further with shivering. Systemic oxygen delivery decreased initially but returned to normal as Hb concentration rose (from 9.4 f 1.5 to 12.5 f 2.2 g/dl). P50 increased normally over the study period. Four of the 11 hypoxemic lambs died during the study. These data show that, in the chronically hypoxemic newborn, systemic oxygen delivery is maintained primarily by a rising Hb. Total body oxygen consumption is maintained at rest but is redistributed away from anabolic requirements and toward cardiorespiratory work. This signal to decrease growth occurs despite less than maximal oxygen extraction at rest. (Pediatr Res 19: 1004Res 19: -1010Res 19: ,1985 developed a model of a common cyanotic heart lesion to assess some of its cardiovascular and metabolic effects on the newborn lamb.Several authors have studied acute hypoxemia in the developing organism and elucidated its effects on general cardiovascular function (1-3), regional blood flow (1, 4, 5), metabolic activity (6, 7), and course of decompensation (1). The effects of sympathetic blockade (8, 9) and decreasing Hb oxygen affinity (10, 11) on the response to acute hypoxemia have also been addressed. Few studies have been performed on the chronically hypoxemic developing organism to understand the change from acute to chronic adaptations and the sequelae of these adaptations. Those studies have involved rodents and calves and have focussed on growth (1 2) and the development of the pulmonary (1 3) and coronary (14) vascular beds.We have designed a model to produce chronic hypoxemia in the newborn lamb and have studied lambs over several days of hypoxemia. We created a model of severe pulmonary stenosis with atrial septal defect. This simulates cyanotic lesions in which total pulmonary blood flow is reduced, which occurs in more than half of the infants with cyanotic heart disease (15). The degree of right ventricular outflow obstruction determines the drop in pulmonary blood flow and thus the magnitude of rightto-left atrial shu...

Redistribution of Regional Blood Flow and Oxygen Delivery in Experimental Cyanotic Heart Disease in Newborn Lambs

“…The increase in hemoglobin increases the blood oxygen-carrying capacity and returns systemic oxygen content to normal. Systemic oxygen delivery can thus be maintained without a chronic increase in cardiac output (5). It is not known, however, whether the redistribution of regional blood flow and oxygen delivery that occurs during acute hypoxemia persists during chronic hypoxemia.…”

“…We produced chronic hypoxemia in newborn lambs by creating pulmonary stenosis and an atrial septal defect, as previously described (5). Briefly, surgery was performed on 13 newborn lambs of mixed western breed during the I st wk of life.…”

“…The decrease in growth may reduce systemic oxygen utilization (3,5). The increase in hemoglobin increases the blood oxygen-carrying capacity and returns systemic oxygen content to normal.…”

“…In a previous study of newborn lambs with experimentally produced cyanotic heart disease, we demonstrated that the major compensations to chronic hypoxemia are a decrease in growth and an increase in hemoglobin concentration (5). The decrease in growth may reduce systemic oxygen utilization (3,5).…”

“…It is not known, however, whether the redistribution of regional blood flow and oxygen delivery that occurs during acute hypoxemia persists during chronic hypoxemia. Therefore, the purpose of the present study was to determine whether regional blood flow and oxygen delivery are redistributed during chronic hypoxemia in the newborn lamb (5).…”