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Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 73 records · Page 4Linked to original sources
PubMed1989

The effects of changes in heart rate and aortic systolic pressure on left ventricular myocardial oxygen consumption in lambs.

To determine whether changes in heart rate and aortic systolic pressure contribute equally to the determination of left ventricular myocardial oxygen consumption, we independently varied heart rate and pressure and compared the resultant oxygen consumption for similar rate-pressure products. In 6 young lambs which underwent atrioventricular node ablation, we varied heart rate by ventricular pacing at 250 beats/min, 300 beats/min, and 120 beats/min while aortic pressure remained stable and varied aortic systolic pressure by infusion of phenylephrine (to 132 +/- 15 mm Hg and 155 +/- 14 mm Hg) and by infusion of sodium nitroprusside (to 79 +/- 6 mm Hg) while heart rate was maintained stable at 200 beats/min. The 3 levels of change in aortic systolic pressure were chosen so that the ratepressure product during the pressure changes matched the rate-pressure product during the heart rate changes. We found that left ventricular myocardial oxygen consumption was the same at all 3 levels of the rate-pressure product whether heart rate was changed and pressure remained stable or pressure was changed and heart rate remained stable. Also, the correlation between oxygen consumption and the rate-pressure product was similar for both heart rate and pressure changes. During nitroprusside infusion at a fixed heart rate, oxygen extraction was significantly lower than during pacing at a heart rate of 120 beats/min when the rate-pressure product was comparable because of the direct vasodilatory effects of nitroprusside. We conclude that heart rate and aortic systolic pressure contribute equally to left ventricular myocardial oxygen consumption at the same rate-pressure product, even though there may be differences in myocardial blood flow and oxygen extraction.

Animals↗
PubMed1989

Effect of cortisol on hepatic gluconeogenesis in the fetal sheep.

To determine whether the prenatal surge in cortisol induces the onset of gluconeogenesis in the fetal sheep, we performed studies in eight fetal sheep of 124 +/- 3 days gestational age. Catheters were inserted chronically in the descending aorta, inferior vena cava, and hepatic and umbilical veins, allowing the measurement of substrate flux across the liver and placenta. Cortisol was infused over a 48-h period, raising plasma cortisol concentrations from 3.5 +/- 2.5 ng/ml to 78 +/- 22 ng/ml at 24 h and 111 41 ng/ml at 48 h. At 24 and 48 h, [14C]lactate was infused into the inferior vena cava, and blood samples were obtained to measure plasma concentrations and specific activities of glucose and lactate. Comparison of the cortisol-treated group with an untreated control group of animals revealed no differences in blood gases, haemoglobin concentrations, or glucose and lactate levels. Similarly, there were no differences between groups in liver oxygen consumption, glucose and lactate flux, or gluconeogenesis from lactate. In two animals we demonstrated hepatic glucose production from lactate. One of these was in active labor at the time of study, and one aborted within hours of the study. We conclude that the prenatal cortisol surge alone is not responsible for the onset of hepatic gluconeogenesis in the perinatal period. However, cortisol may have a permissive action, promoting hepatic gluconeogenesis in response to other hormonal stimuli.

Animals↗
PubMed1989

Perinatal onset of hepatic gluconeogenesis in the lamb.

Hepatic gluconeogenesis does not occur in the unstressed fetal sheep. After birth, in addition to glycogenolysis, the newborn lamb must eventually initiate gluconeogenesis to maintain glucose homeostasis. The regulation and time course of this transition have not been defined. We studied six animals in an acute preparation before and after delivery to determine hepatic lactate and glucose uptake, hepatic gluconeogenesis from lactate, and plasma catecholamine and cortisol concentrations. After a priming dose, continuous infusion of [14C]lactate provided tracer substrate for calculations of gluconeogenesis in the fetus and then for ten hours after delivery in the newborn lamb. The radionuclide-labelled microsphere method was used to measure hepatic blood flow. Appreciable gluconeogenesis was not present during the fetal period. Following delivery, the newborn lambs began to produce significant quantities of glucose from lactate at 6 h of age (1.37 +/- 0.84 mg.min-1.100 g-1 min-1 x 100 g-1 liver), when gluconeogenesis from lactate accounted for 22% of hepatic glucose output. Despite the onset of gluconeogenesis, postnatal lambs had blood glucose concentrations that remained less than fetal levels of 23.4 +/- 12.1 mg/dl for the duration of the 10-h study. Plasma norepinephrine concentration was 1380 +/- 1145 pg/ml in the fetus and fell by 2 h after birth. Plasma epinephrine concentrations were highest at 15 min after birth (205 +/- 262 pg/ml), but remained quite low for the remainder of the study. Plasma cortisol concentrations did not vary over the course of study, ranging from 40 to 50 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Effect of beta-adrenergic receptor blockade on responses to acute hypoxemia in lambs.

We studied the effects of beta-adrenergic receptor blockade on general circulatory and metabolic responses to moderate (FIO2 = 0.09) acute hypoxemia in newborn (protocol 1) and 3-wk-old (protocol 2) lambs, and on regional blood flow distribution in newborn lambs (protocol 1). Via a left thoracotomy we placed an electromagnetic flow transducer around the ascending aorta and inserted various vascular catheters. After 2 days of recovery, the lambs were studied. In protocol 1, we measured cardiovascular variables and regional blood flow distribution during control conditions, after 45 min of acute hypoxemia, and after 0.5 mg/kg of propranolol during acute hypoxemia. In protocol 2, we measured cardiovascular variables during control conditions and after 45 min of acute hypoxemia with and without propranolol pretreatment. In both groups, propranolol limited the increase in cardiac output and heart rate caused by hypoxemia, and thus decreased oxygen delivery. However, propranolol also decreased oxygen consumption so that pulmonary arterial pO2 was either higher (protocol 1) or the same (protocol 2) as during acute hypoxemia alone. Neither metabolic acidosis nor hypothermia ensued. In protocol 1, propranolol decreased renal, carcass, and most importantly, myocardial blood flows. However, myocardial O2 consumption also fell, coronary sinus pO2 increased, and blood was redistributed toward the subendocardium, suggesting that myocardial perfusion improved. Thus, beta-adrenergic receptor blockade during acute moderate hypoxemia may have a beneficial effect by reducing total body and myocardial oxygen demand in excess of the reduction in oxygen delivery.

Acute Disease↗
PubMed1988

Chronic anemia in the newborn lamb: cardiovascular adaptations and comparison to chronic hypoxemia.

The cardiovascular adaptations to chronic anemia were studied in the newborn lamb and then compared with the adaptations to chronic hypoxemia. Eight chronically instrumented newborn lambs underwent repeat isovolemic exchange transfusions to maintain their Hb concentrations at 60% of normal for age. Hemodynamic studies were performed twice weekly for 2 wk after which time regional blood flows were measured using radionuclide-labeled microspheres. The major compensatory responses after 2 wk of anemia were moderate increases in heart rate (229 +/- 20 versus 187 +/- 15 beats/min) and cardiac output (226 +/- 36 versus 165 +/- 38 ml/kg/min), an increase in fractional extraction of oxygen (65 versus 40%), and a redistribution of regional blood flow. Blood flows to the heart and brain increased whereas blood flows to the viscera and carcass did not change. These compensatory responses were different from those that occur during chronic hypoxemia: specifically, cardiac output did increase, growth was not suppressed, and the pattern of redistribution of regional blood flows was different. The dissimilar effects of anemia (decreasing systemic oxygen content) versus hypoxemia (decreasing systemic oxygen tension) on local tissue receptors and peripheral chemoreceptors may account for these differences.

Adaptation, Physiological↗
PubMed1988

Regulation of cardiac output with controlled heart rate in newborn lambs.

To determine the factors regulating cardiac output in newborn lambs and to examine the effects of age after birth, we altered heart rate, afterload, preload, and myocardial contractility in eight younger lambs, 5 to 13 days old, and seven older lambs, 15 to 36 days old. To control heart rate, we ablated the atrioventricular node by injecting formalin into the region of the node, and paced the right ventricle at a baseline heart rate of 200 beats/min. After the lambs recovered from surgery, we performed two protocols. In the first protocol we assessed the effects of changing heart rate by pacing the ventricle at various rates. We also examined the effect of altering afterload and preload at a fixed heart rate: afterload was increased by infusing phenylephrine and decreased by infusing nitroprusside. Preload was increased by infusing blood or 0.9% NaCl solution over 2 min. In the second protocol, we increased myocardial contractility by infusing isoproterenol at a fixed heart rate. Increasing heart rate above baseline levels caused no significant increase in cardiac output in the younger lambs (3.9 +/- 4.0%, mean +/- SD), and only small increases in the older lambs (11.4 +/- 6.7%). Decreasing heart rate, however, resulted in a progressive decrease in cardiac output in both groups of lambs. Decreasing afterload caused no significant increase in cardiac output in the younger lambs (1.4 +/- 14.0%) and only a small increase in the older lambs (11.1 +/- 1.9%).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

The cardiovascular effects of isoflurane in lambs.

The effects of 1.0 and 1.5 minimum alveolar concentrations (MAC) of isoflurane on mean systemic arterial pressure, heart rate, stroke volume, cardiac output, total body oxygen consumption, myocardial oxygen consumption, and regional distribution of blood flow were studied in newborn lambs. Fractional extraction of oxygen for the total body and for the myocardium were calculated. MAC for isoflurane was first determined in eight lambs less than 10 days old. The mean value obtained was 1.51%. Six different lambs were used for cardiovascular study. Heart rate, stroke volume, cardiac output, and mean systemic arterial pressure decreased significantly during isoflurane anesthesia. Mean systemic arterial pressure and cardiac output decreased in a dose-dependent manner. Heart rate decreased significantly at 1.0 MAC isoflurane, but no further at 1.5 MAC. Stroke volume decreased only at 1.5 MAC. Cardiac output and total body oxygen consumption decreased by similar amounts at 1.0 MAC. Although cardiac output fell further at 1.5 MAC, oxygen consumption did not. Fractional extraction of oxygen increased only at 1.5 MAC. Myocardial blood flow and oxygen consumption decreased in parallel at 1.0 MAC, with no significant change during 1.5 MAC. Myocardial fractional oxygen extraction did not change. Although blood flow to all six body regions decreased significantly from control at both concentrations of isoflurane, blood flow to all organs except the adrenal did not differ significantly during 1.0 and 1.5 MAC. The authors conclude that a decrease in oxygen requirement during isoflurane anesthesia results in an appropriate decrease in oxygen delivery, with no apparent diversion of cardiac output from non-vital to vital organs.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Effects of cord compression on fetal blood flow distribution and O2 delivery.

We used the radionuclide microsphere technique in nine fetal lambs to examine the effect of partial cord compression on distribution of cardiac output and O2 delivery to fetal organs and venous flow patterns. With a 50% reduction in umbilical blood flow the fraction of fetal cardiac output distributed to the brain, heart, carcass, kidneys, and gastrointestinal tract increased. Pulmonary blood flow fell. O2 delivery to the brain and myocardium was maintained but was reduced to peripheral, renal, and gastrointestinal circulations. Hepatic blood flow decreased and O2 delivery fell by 75%. The proportion of umbilical venous blood passing through the ductus venosus increased from 43.9 to 71.8%. The preferential distribution of ductus venosus blood flow through the foramen ovale was enhanced (29.4 vs. 47.2%) and the proportion of O2 delivery to upper body organs derived from the ductus venosus increased (33.2 vs. 49.4%). Abdominal inferior vena caval blood flow increased, and it was also preferentially distributed through the foramen ovale (21.9 vs. 44.2%) and constituted the major fraction of the arterial blood supply to the upper body organs (16.5 vs. 36.4%). Thus cord compression modified the distribution of cardiac output and the patterns of venous returns in the fetus. This pattern of circulatory response differs from that observed with other causes of reduced O2 delivery.

Animals↗
PubMed1987

Cardiorespiratory response to cyanide of arterial chemoreceptors in fetal lambs.

Cardiorespiratory response to the stimulation of the carotid and aortic receptors by sodium cyanide was examined in fetal lambs in utero at 0.8 (120 days) gestation. Injections of 50-400 micrograms cyanide into the inferior vena cava or the carotid artery of intact fetuses elicited bradycardia and respiratory responses that varied from a single gasp to rhythmic respiratory movements but no significant change in arterial blood pressure. Carotid sinus denervation eliminated the cardiorespiratory response to intracarotid injection of cyanide and sinoaortic denervation abolished the response to inferior vena caval injection. It is concluded that in fetal lamb in utero the aortic and carotid bodies are active, and hypoxic stimulation of these chemoreceptors results in cardiorespiratory response characterized by slowing of fetal heart rate, respiratory effort, and no consistent change in arterial blood pressure.

Animals↗
PubMed1987

Redistribution of regional blood flow and oxygen delivery in experimental cyanotic heart disease in newborn lambs.

Redistribution of regional blood flow is an important compensatory response to acute hypoxemia which preserves oxygen delivery to the most vital organs. It is not known if this change in blood flow persists when hypoxemia is prolonged, as occurs in cyanotic congenital heart disease. Chronic hypoxemia was produced in newborn lambs by creating pulmonary stenosis and an atrial septal defect. Oxygen saturation was maintained at 60-70% of control for 2 wk. Distribution of cardiac output was then measured with radionuclide-labeled microspheres. As compared with control, chronic hypoxemia did not alter total cardiac output. Regional blood flow was redistributed, however, the pattern of this redistribution was different from that seen during acute hypoxemia. Myocardial and cerebral blood flows, which increase during acute hypoxemia, return to control levels during chronic hypoxemia. Renal, splenic, gastrointestinal, carcass, and skin blood flows remain decreased. Hemoglobin gradually increases so that after 2 wk of hypoxemia total systemic oxygen delivery returns toward control. However, oxygen delivery to all organs except the heart and brain is reduced. Thus, although cardiac output and total systemic oxygen delivery return toward normal during chronic hypoxemia, these measurements may not reflect important regional variations in blood flow and oxygen delivery. Decreased oxygen and substrate delivery to the gastrointestinal tract, liver, and carcass may account for the alterations of metabolism and growth seen in the newborn with cyanotic congenital heart disease.

Animals↗
PubMed1987

Effects of birth-related events on central blood flow patterns.

We determined the effects of three components of the birth process on central blood flow patterns in fetal sheep. We instrumented 16 fetal sheep at 133.0 +/- 1.2 days gestation, inserting various intravascular catheters, intubating the trachea, and placing an inflatable balloon around the umbilical cord. After 2-3 days, we determined central blood flow patterns using radionuclide-labeled microspheres under control conditions, during positive pressure ventilation without oxygenation, during ventilation with 100% O2, and after umbilical cord occlusion. The foramen ovale right to left shunt was essentially abolished, decreasing from 102 +/- 48 to 66 +/- 40 ml/min/kg with ventilation, and to only 13 +/- 10 ml/min/kg with oxygenation. The ductus arteriosus right to left shunt decreased progressively, from a control level of 224 +/- 64 to 6 +/- 10 ml/min/kg after umbilical cord occlusion. A ductus arteriosus left to right shunt appeared with oxygenation (41 +/- 26 ml/min/kg) and increased to 65 +/- 43 ml/min/kg after cord occlusion. Left ventricular output increased progressively as a percentage of combined ventricular output (from a control value of 34.8 to 59.5% after cord occlusion), and increased absolutely with ventilation (from 134 +/- 44 to 211 +/- 87 ml/min/kg). However, right ventricular output decreased (from a control value of 258 +/- 75 to 144 +/- 36 ml/min/kg after cord occlusion) so that combined ventricular output did not change. Although the transition from the fetal to neonatal circulatory pattern was accomplished by simulating these three components of the birth process, none is alone responsible for the large increase in combined ventricular output normally seen at birth.

Animals↗
PubMed1987

Effects of birth-related events on blood flow distribution.

At birth, the cardiovascular system changes dramatically; arterial blood pressure, heart rate, and cardiac output increase, and blood flow distribution undergoes regional changes. To determine whether these changes are related to certain events occurring at birth, we studied 18 chronically instrumented fetal sheep at 133-138 days gestational age. We measured fetal vascular pressures and heart rate and injected radionuclide-labeled microspheres to determine combined ventricular output and its distribution. Rhythmic ventilation of the fetuses with a gas mixture that produced no change in arterial blood gases decreased heart rate slightly from 173 +/- 25 to 152 +/- 16 beats/min, but changed neither mean arterial blood pressure nor combined ventricular output. Ventilation with oxygen decreased mean descending aortic and pulmonary arterial pressures, but had no significant effect on heart rate or combined ventricular output; subsequent umbilical cord occlusion had no significant effect on these variables. There was a redistribution of blood flow, however. Ventilation alone increased pulmonary blood flow from 159 +/- 68 to 641 +/- 513 ml.min-1.100 g wet weight-1, and oxygenation increased it further to 1040 +/- 426. Ventilation alone and ventilation with O2 decreased blood flow to most other fetal organs, notably the adrenal glands, brain, and heart, in a manner related to changes in arterial oxygen tension. Occlusion of the umbilical cord increased blood flow to the adrenal glands and brown fat, and also to the liver from the portal vein and hepatic artery. The changes in regional blood flow initiated by ventilation, oxygenation, and umbilical cord occlusion are similar to those occurring at birth and may play an important role in postnatal adaptation.

Animals↗
PubMed1987

Red blood cell volume of the pig fetus.

A non-radioactive fluorescent excitation analysis technique was used to measure total red blood cell volume in 31 unanaesthetised pig fetuses in utero. Red blood cell volume (y in ml) was closely related (r = 0.94) to fetal bodyweight (x in g): where y = 2.92 + 0.0291x. Average red blood cell volume was 34 +/- 1 ml kg-1 fetal bodyweight. Average estimated (total) blood volume was 117 +/- 3 ml kg-1 fetal bodyweight. It was concluded that this non-radioactive indicator dilution measurement of red blood cell volume is a significant advance over the established 51Cr method, and that measurement of red blood cell volume may be used to estimate fetal bodyweight in utero.

Animals↗
PubMed1986

Developmental alterations in hepatic UDP-glucuronosyltransferase. A comparison of the kinetic properties of enzymes from adult sheep and fetal lambs.

The kinetic properties of hepatic microsomal UDP-glucuronosyltransferase were studied in sheep in the perinatal period, using acetaminophen as the aglycone. Kinetic analyses indicated that activity at Vmax was significantly less in fetal microsomes (113, 135 or 141 days) as compared with the adult sheep. However, these differences between fetal and adult animals were not due simply to smaller amounts of UDP-glucuronosyltransferases catalyzing conjugation of acetaminophen in fetuses versus adults. Thus, the kinetic properties of UDP-glucuronosyltransferase(s) were different in fetus and adult. The "fetal" versus "adult" enzyme had a higher affinity for UDP-glucuronic acid, but a poorer affinity for acetaminophen. Furthermore, enzyme in fetal liver (113 days of gestation) was activated about 30% by the allosteric effector UDP-N-acetylglucosamine, whereas enzyme in adult liver was activated by 500%. These differences between fetal and adult enzymes diminished just prior to parturition (141-day fetus). Enzyme in microsomes from the 141-day fetus responded to UDP-N-acetylglucosamine-like enzyme in adult microsomes and had affinities for substrates that were similar to "adult" enzymes. These data indicate that maturation of the system that glucuronidates acetaminophen is a complex process. It may involve the expression in fetuses of a type of UDP-glucuronosyltransferase that is different from that expressed in the adult. An alternative but not mutually exclusive possibility is that maturation of the glucuronidation system involves modification of enzyme function by alteration of the phospholipids in the immediate environment of UDP-glucuronosyltransferase within the microsomal membrane.

Animals↗
PubMed1986

Cardiovascular effects of d-tubocurarine and pancuronium in newborn lambs during normoxia and hypoxia.

Nondepolarizing muscle relaxants are administered to hypoxic neonates (including those with severe cyanotic congenital heart disease) to reduce oxygen consumption. However, it is unknown whether paralysis actually reduces oxygen consumption or whether the drugs used affect the cardiovascular system of neonates. Therefore, we studied the effects of d-tubocurarine and pancuronium induced muscle paralysis on oxygen consumption, cardiac output, and tissue oxygen delivery in healthy normoxic and hypoxic 1- to 3-day-old lambs. We measured intravascular pressures, cardiac output and its distribution (microspheres), and blood gases and pH during: 1) spontaneous respiration with room air (control); 2) spontaneous respiration with a Pao2 of 27-33 mm Hg (hypoxia); 3) mechanical ventilation with room air; 4) mechanical ventilation with room air and paralysis with d-tubocurarine (0.3 mg/kg) or pancuronium (0.1 mg/kg); and 5) mechanical ventilation with hypoxia and paralysis. Mechanical ventilation, with or without muscle paralysis, had no effect on the oxygen delivery or oxygen consumption of normoxic animals. Hypoxia and spontaneous ventilation had no effect on oxygen consumption, but hypoxia, paralysis, and mechanical ventilation reduced it 35% (p less than 0.002 d-tubocurarine) and 50% (p less than 0.001 pancuronium). Cardiac output was unaffected by oxygenation, mechanical ventilation, or muscle paralysis. However, blood flow to the brain and heart increased during hypoxia, which maintained normal oxygen delivery to these organs. During hypoxia and spontaneous ventilation, mean pulmonary arterial pressures increased 34% (d-tubocurarine) and 54% (pancuronium) above control; during hypoxia, muscle paralysis, and mechanical ventilation, it increased 81%.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Oxygenation does not stimulate hepatic gluconeogenesis in fetal lambs.

We have previously shown that the healthy fetal lamb liver does not release glucose and does not demonstrate gluconeogenesis. Shortly after birth, however, the liver releases glucose both by glycogenolysis and by gluconeogenesis. Previously it has been suggested that increased oxygen availability stimulates hepatic gluconeogenesis at birth. To test this hypothesis, we increased fetal arterial blood pO2 by ventilating the fetus with high oxygen gas mixtures in utero. We placed intravascular catheters in the right or left hepatic vein, umbilical vein, inferior vena cava, and descending aorta and inserted a large polyvinyl tube into the trachea of seven fetal lambs at 134 +/- 2.2 days gestation. Studies were done several days after surgery. 14C-lactate was infused intravenously and 14C-glucose concentrations were measured in hepatic venous and umbilical venous blood during a control period, during ventilation with 5% CO2, 3% O2, 92% N2, and then during ventilation with 5% CO2 and 95% O2. The difference between these two measurements represented hepatic gluconeogenesis. Arterial blood glucose concentrations and blood gases were also measured during each study period. Ventilation with 3% O2 did not significantly change arterial PO2 but ventilation with 95% oxygen increased mean arterial pO2 from a control of 16.7 to 156.3 torr. Mean arterial blood glucose concentration increased significantly from a control of 11.9 to 17.6 mg/dl during ventilation with 3% O2 and to 19.1 mg/dl during ventilation with 95% O2. However, the hepatic-umbilical venous 14C-glucose concentration difference was not significant when control values were compared with each ventilation period. We conclude that an acute increase in fetal oxygenation does not stimulate hepatic gluconeogenesis in near-term fetal lambs.

Animals↗