J. Ross Milley

Retinal and Choroidal Blood Flows in Hypoxic and Hypercarbic Newborn Lambs

Summary: We studied the effect of changes in the arterial tensions of oxygen and carbon dioxide on blood flow to the retinal (RBF) and choroidal (ChBF) capillary beds in 20 lambs. One to three days after placement of catheters in the left ventricle, abdominal aorta, and brachiocephalic artery, different gas mixtures were delivered to a bag enclosing the lambs head. One group of lambs was studied at normal and low oxygen tensions while normocarbic, and another group was studied at normal and high carbon dioxide tensions while normoxic. RBF and ChBF were measured using the radioactive microsphere technique. RBF increased as PaO2 and, thus, arterial oxygen content ([O2]a) fell; in contrast, ChBF was not related to [O2]a. Oxygen delivery to the capillary bed of the retinal artery (i.e., RBF × [O2]a) was independent of arterial oxygen content because the change in [O2]a was balanced by a reciprocal change in RBF. Oxygen delivery to the choroidal capillary bed, however, rose with [O2]a because there was no reciprocal decrease in ChBF. Both RBF and ChBF increase as arterial carbon dioxide tension rose. Although an increase in arterial carbon dioxide tension produced an increase in RBF with no change in [O2]a, oxygen delivery to the retinal capillaries rose. Similarly, oxygen delivery to the capillaries of the choroid rose with carbon dioxide tension. Oxygenation of retinal tissue, which depends on oxygen diffusion from both the retinal and choroidal capillary beds, may change with variations in arterial oxygen content (increase in oxygen delivered to the choroidal capillary bed) or arterial carbon dioxide tension (increase in oxygen delivered to both the retinal and choroidal capillary beds).

Neurogenic pulmonary edema in childhood

Three patients presenting with pulmonary edema associated with head trauma and increased intracranial pressure are described. Pulmonary edema is a clearly recognized complication of head trauma; the pathogenic mechanisms appear to be regulated by increased intracerebral pressure, sympathetically induced vascular hypertension, and increased pulmonary capillary permeability. If there is evidence that neurogenic pulmonary edema is the underlying etiology, therapeutic modalities should be directed at reducing intracranial pressure and strict attention paid to the interaction between intrathoracic and intracranial pressures in order to avoid the high mortality rate associated with this condition.

Effect of insulin on the distribution of cardiac output in the fetal lamb.

ABSTRACT. Three to five measurements of fetal cardiac output and its distribution were made using radiolabeled microspheres in each of 12 sheep fetuses in whom fetal plasma insulin concentration was varied by exogenous infusion of insulin to the fetus. Blood concentrations of oxygen and glucose as well as blood gases, pH, hematocrit, and plasma insulin concentrations were also measured. Both fetal arterial oxygen content and whole blood glucose concentration fell as fetal insulin concentration rose. Fetal cardiac output rose as insulin concentration increased and was accompanied by an increase in fetal heart rate. Increased insulin concentration was associated with increased flow to the heart, stomach, placenta, and carcass while blood flow to the fetal brain, lungs, liver, kidneys, spleen, and intestines was not affected. As plasma insulin concentration rose, the percentage of the cardiac output distributed to the fetal heart and upper carcass increased; that distributed to the fetal brain, lungs, liver, stomach, intestines, and lower carcass remained unchanged; while that distributed to the kidneys, spleen, and placenta decreased. When expressed as a fraction of cardiac output, an additional 7% (from 39 to 46%) of the cardiac output was distributed to carcass over the range of insulin concentrations studied. Most of the increased portion of the fetal cardiac output distributed to the fetal carcass during hyperinsulinemia was accounted for by a decrease in the percentage of fetal cardiac output perfusing the placenta.ABSTRACT. Three to five measurements of fetal cardiac output and its distribution were made using radiolabeled microspheres in each of 12 sheep fetuses in whom fetal plasma insulin concentration was varied by exogenous infusion of insulin to the fetus. Blood concentrations of oxygen and glucose as well as blood gases, pH, hematocrit, and plasma insulin concentrations were also measured. Both fetal arterial oxygen content and whole blood glucose concentration fell as fetal insulin concentration rose. Fetal cardiac output rose as insulin concentration increased and was accompanied by an increase in fetal heart rate. Increased insulin concentration was associated with increased flow to the heart, stomach, placenta, and carcass while blood flow to the fetal brain, lungs, liver, kidneys, spleen, and intestines was not affected. As plasma insulin concentration rose, the percentage of the cardiac output distributed to the fetal heart and upper carcass increased; that distributed to the fetal brain, lungs, liver, stomach, intestines, and lower carcass remained unchanged; while that distributed to the kidneys, spleen, and placenta decreased. When expressed as a fraction of cardiac output, an additional 7% (from 39 to 46%) of the cardiac output was distributed to carcass over the range of insulin concentrations studied. Most of the increased portion of the fetal cardiac output distributed to the fetal carcass during hyperinsulinemia was accounted for by a decrease in the percentage of fetal cardiac output perfusing the placenta.

The effects of sodium nitroprusside on blood flow and oxygen delivery to the organs of the hypoxemic newborn lamb.

ABSTRACT: Vasodilators are used in newborns under conditions where hypoxia may be prominent. To study the effects of vasodilator therapy on organ oxygen delivery we measured blood flow (using radioactive microspheres) and arterial oxygen content in six chronically catheterized newborn lambs. Cardiac output and its distribution were measured during normoxia, hypoxia (10% O2 and 5% CO2), and hypoxia with a nitroprusside infusion. Hypoxia decreased oxygen content but did not change heart rate, mean blood pressure, or cardiac output. When nitroprusside was infused during hypoxemia, oxygen content and heart rate were not affected, but mean arterial blood pressure fell (39% decrease). During hypoxemia, blood flow increased to the heart, brain, and carcass but decreased to the gastrointestinal tract. When nitroprusside was infused during hypoxemia, blood flow decreased to the heart, brain, kidneys, and carcass. Oxygen delivery (arterial O2 content × blood flow) decreased to the brain as well as to kidneys, stomach, and carcass when nitroprusside was given to the hypoxemic lamb.

1376 CIRCULATORY EFFECTS OF HYPERINSULINEMIA IN THE NEAR TERM OVINE FETUS

Ovine fetal hyperinsulinemia is associated with increased oxygen consumption, increased glucose uptake and decreased arterial O2 content. We used eight mixed breed ewes with 114-132 day singleton pregnancies to measure the magnitude and distribution of fetal cardiac output in order to define the causes of insulin-induced hypoxemia. During an uninfused control period and again after 12, 24 and 48 hours of exogenous insulin infusion (0.05U/kg/hr), we measured umbilical vein-artery whole blood concentrations of glucose and oxygen. We used the distribution of each of four microsphere injections to determine total cardiac output and organ blood flow. Insulin infusion was associated with increasing insulin concentration following a 12 hour lag period. We confirmed an increase in cardiac output (+19%, P<0.02) and a progressive fall in arterial O2 content (0.33mM to 0.23mM, P<.001). During insulin infusion, blood flow increased to the brain (+50%, P<0.05), adrenal (+56%, P<0.01), and carcass (+44%, P<0.02). Placental blood flow did not change during infusion and fell when expressed as a percentage of cardiac output (45% to 34%, P<.002). The hypoxemia during insulin infusion occurs as a result of increased O2 consumption without a corresponding increase in placental blood flow. If similar effects occur in humans, hyperinsulinemic hypoxia may account for the near term fetal and neonatal mortality among women with poorly controlled diabetes.

273 THE EFFECT OF EXOGENOUS INSULIN ON OVINE FETAL GBOWTH

Macrosomia in association with a hyperinsulinemic intrauterine environment is found in the fetus of the diabetic mother. We have studied the ovine fetus to demonstrate directly that exogenous insulin administration accelerates fetal growth. Seven mixed breed ewes with radiologically confirmed, nondiscordent twin fetuses were used. Insulin was infused at 90±50 mu/kg/day to one randomly selected fetus while the other twin was infused with saline as control. Infusion was continued for 14.9±1.5 days during which there were no differences in serum glucose, PO2, PCO2, pH or hematocrit between infused and control fetuses. Studies of insulin binding to erythrocyte receptors revealed no differences in maximum percentage binding, mean empty site binding affinity, receptor concentration or the concentration of insulin which inhibited (125I) iodoinsulin by 50%. Following infusion, analysis of fetal growth demonstrated no differences in weight, length or organ weights between control and experimental animals. No effects of insulin infusion were found on tissue water, protein, RNA, DNA or glycogen. We have demonstrated that small amounts of exogenous insulin do not alter the normal pattern or rate of ovine intrauterine growth over a 15 day infusion period. It is possible that insulin at physiologic concentrations has little role in the regulation of fetal growth.