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We previously observed young lambs to be more tolerant of hypoxia; compared with older lambs, they accumulate lactate at a slower rate during comparable reduction in cardiac output, and have a greater percent decrease in cardiac output before onset of systemic lactate accumulation. To determine the mechanism of lactic acidosis and the cause for this "tolerance," we reduced cardiac output progressively in seven chronically catheterized conscious lambs (16.4 + 5.1 d) and measured hepatic and gastrointestinal (GI) blood flow (radioactive microspheres) and delivery, uptake, and extraction of lactate and O2. Hepatic O2 consumption declined proportionately below a critical hepatic O2 delivery (approximately 2 mL O2/min/kg), corresponding to the systemic O2 delivery associated with the onset of systemic lactate accumulation. As hepatic O2 delivery decreased below the critical value, there was initially net hepatic lactate uptake and then a change to net production when the O2 delivery decreased below approximately 1 mL O2/min kg. The GI tract had net lactate production at rest, but surprisingly switched to lactate uptake as cardiac output decreased. The mechanism of lactic acidosis was failure of hepatic lactate uptake to increase despite increased hepatic lactate delivery, as reported in adults subjects. However, in contrast, there was "true" hepatic dysfunction and lactate production only at the lowest levels of cardiac output, after onset of systemic lactate accumulation. Moreover, we speculate that tolerance of young lambs to hypoxia is at least due to two factors: 1) hepatic lactate uptake is maintained beyond the "critical" O2 delivery and fall in hepatic O2 consumption, and 2) there is a switch to lactate uptake by the GI tract serving to buffer the lactate.

We chronically catheterized 15 newborn lambs (9.5 +/- 2.8 days) and measured the distribution of cardiac output by the radionuclide-microsphere technique at hematocrits ranging from 10 volumes % to 55 volumes %. Seven animals were made progressively anemic and eight polycythemic by means of exchange transfusions. Cardiac output and heart rate increased with decreasing hematocrit while whole body oxygen consumption showed a small decrease during severe anemia. Both cerebral and cardiac blood flow markedly increased during anemia which assured a relatively stable oxygen delivery to both organs. The changes seen for blood flow to the carcass (skin, bones, and muscle) were predictable from the effects of blood viscosity: small decreases in flow at the highest hematocrits and small increases in flow at the lowest hematocrits. Consequently, oxygen delivery was as low as 1 ml of oxygen/min/100 g at a hematocrit of 10 volumes %. Renal blood flow remained unchanged while oxygen delivery fell when hematocrit was decreased. Hepatic oxygenation was measured using a modification of the Fick principle. Hepatic blood flow showed only a small decrease as hematocrit increased and changed minimally during anemia resulting in a falling delivery of oxygen with anemia. A stable hepatic oxygen consumption was assured by a marked increase in oxygen extraction during anemia. Two differing organ responses to changes in hematocrit can be seen in the newborn: the brain and heart vary blood flow to assure an adequate delivery of oxygen while a number of other organs show less blood flow regulation and, most likely, vary oxygen removal from blood.(ABSTRACT TRUNCATED AT 250 WORDS)

SUMMARY We evaluated the circulation of the liver and ductus venosus, using the radionuclide-labeled mkrosphere technique, in 24 chronically prepared fetal lambs. We placed catheters in fetal descending aorta and inferior vena cava, and hi a carotid artery and an umbilical vein; in 11 fetuses, we aho Inserted a catheter hi a mesenteric vein that drained into the portal vein. After allowing 2-4 days for recovery from the stresses of anesthesia and operation, we measured blood flow to the fetal liver and hs various lobes and through the ductus venosus. Total Mood flow to the liver was 435 ± 122 ml/min per 100 g liver (mean ± SD), of which hepatic arterial flow represented 9%, portal venous flow 18%, and umbilical venous flow 73%. Hepatic arterial and umbilical venous flows were approximately equally divided between left and right lobes, although portal blood flow was directed almost exclusively to the right lobe. The right lobe received 40% more total blood flow than the left, even though the left lobe weighed more than the right. Approximately 53% of umbilical venous blood flow but less than 9% of portal venous blood flow entered the ductus venosus; umbilical venous flow therefore accounted for more than 98% of ductus venosus blood flow. Ductus venosus flow showed a strong linear correlation with umbilical blood flow. However, there was no relationship between ductus venosus flow and gestational age. The results suggest that the liver receives a large Mood flow primarily because of a large umbilical venous contribution. It is not dear whether the fetal liver requires this large flow and peculiar lobar distribution for normal function and growth. It is unlikely, however, that the ductus venosus functions actively to maintain a stable blood flow to the fetal liver. THE LIVER of the fetus receives its blood supply from the hepatic artery, portal vein, and umbilical vein. Total blood flow to the fetal liver must be high, because a large umbilical venous blood flow passes through the liver. Nevertheless, the actual flow that reaches the liver from all three vascular sources has not been measured previously. The relative contributions of hepatic arterial and portal and umbilical venous blood flows to the various lobes of the liver also have not been studied quantitatively. Anatomically, the left lobe of the liver is supplied by branches of the umbilical vein, while the right lobe is supplied by portal venous branches 11 (Fig. 1). Except for occasional small branches, no umbilical blood vessels extend into the right lobe, and no portal blood vessels reach the left lobe. Branches of the hepatic artery supply both lobes, but arterial flow to the whole liver is small.

We determined hepatic arterial (QHA) and portal venous (Qpv) blood flows and calculated, utilizing the Fick principle, net hepatic glucose production (PGLUC), O2 delivery (DO2), O2 consumption (VO2), and O2 extraction (VO2/DO2), in 7 chronically catheterized lambs (9-15 d). Studies were done with the lambs fasted and at 1, 2, 3, 4, and 6 hr postprandially. We measured O2 contents (Lex-O2-Con), blood flows (radioactive microspheres), and glucose (glucose oxidase). The table indicates mean results. (* = significantly different from fasting) Our results show that the VO2 of the neonatal liver decreases postprandially. This decreased VO2 is associated with a decreased O2 extraction rather than a decrease in DO2 or hepatic blood flow. Since glucose production is increasing at a time when hepatic oxygen consumption is decreasing, these data indicate that hepatic metabolism shifts postprandially to less oxygen-dependent processes.