Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 37 records · Page 2Linked to original sources

PubMed1993

Accuracy of right ventricular output estimated by Doppler echocardiography in the sheep fetus.

OBJECTIVE: Our goal was to determine whether Doppler ultrasonographic estimation of fetal right ventricular output was accurate enough to evaluate fetal cardiac performance before the technique can be applied with confidence to the human fetus. The accuracy of this method has not been validated experimentally. STUDY DESIGN: We compared the right ventricular output measured by Doppler echocardiography with that determined from a transit-time ultrasonic flowmeter placed around the fetal pulmonary trunk and to that determined by microsphere technique. We obtained 72 Doppler flow measurements and 16 microsphere flow measurements in six fetuses. RESULTS: There was a fair correlation between cardiac output estimated by Doppler echocardiography performed transabdominally and that determined by a transit-time flowmeter (r = 0.76). The correlation was excellent when Doppler echocardiography was performed by the trans-uterine approach (r = 0.94). There was also an excellent correlation between right ventricular output determined by a transit-time flowmeter and that by microsphere technique (r = 0.94). CONCLUSION: Doppler echocardiographic estimation of fetal right ventricular cardiac output is thus feasible and accurate.

Animals↗

PubMed1993

Effects of lung distension and spontaneous fetal breathing on hemodynamics in sheep.

In previous studies, we determined that pulmonary ventilation and oxygenation were largely responsible for increasing pulmonary blood flow and for altering central blood flow patterns but could not account for the increase in combined ventricular output (the sum of left and right ventricular outputs) that usually occurs after birth. We had ventilated fetuses with oscillating positive pressures; the possibility that high intrathoracic pressures adversely affected cardiac output could not be ruled out. To determine the effects of negative intrathoracic pressure ventilation, we occluded the umbilical cord of nine long-term instrumented fetal sheep at 135 +/- 1.2 d gestation while introducing humidified oxygen gas intratracheally. This stimulated continuous fetal respiratory activity, which resulted in negative intrathoracic pressures and increased fetal oxygenation. Pulmonary blood flow increased from 121 +/- 60 to 901 +/- 139 mL.min-1.100 g-1 (mean +/- SD) and descending aortic blood pressure increased from 7.0 +/- 1.2 to 9.6 +/- 2.0 kPa. Central blood flow patterns were altered so that right to left shunting of blood through the foramen ovale and ductus arteriosus was abolished and a left to right shunt developed across the ductus arteriosus. However, cardiac output did not increase significantly. This may be related, in part, to the increase in afterload. It is clear that pulmonary ventilation and oxygenation are the major factors responsible for changing pulmonary blood flow and central blood flow patterns at birth. Other birth-related events, such as a decrease in environmental temperature and an increase in metabolic rate, are likely to induce cardiac output to increase.

Animals↗

PubMed1993

Sympathoadrenal, metabolic, and regional blood flow responses to cold in fetal sheep.

Because environmental temperature falls when the fetus is delivered from the uterus, the role of cold in stimulating cardiovascular and sympathoadrenal responses at the time of birth was examined in fetal lambs. In eight fetuses (gestational age 140 +/- 2 d), catheters were inserted into hind-limb and neck arteries and veins, and into an umbilical vein. After returning the fetus to the uterus and administering a muscle relaxant (succinylcholine chloride), blood gases, glucose and lactate concentrations, and plasma catecholamine and atrial natriuretic peptide concentrations were measured. Fetal combined ventricular output and organ blood flows were measured by the radionuclide-labeled microsphere technique. Measurements were repeated after delivering the fetus into a warm water bath (40 degrees C) and at 15 and 30 min after the bath temperature was cooled to 25 degrees C. Fetal cooling stimulated a sympathoadrenal response, which was manifested by an immediate increase in heart rate and arterial blood pressure, a rise in atrial natriuretic peptide, and modest increase in norepinephrine concentration. Contrary to earlier reports that investigated the effect of cold on fetal lambs using an intrauterine cooling coil, we did not find a decrease in fetal arterial oxygen tensions and pH, an increase in plasma glucose and lactate concentrations, or changes in fetal oxygen consumption. Combined ventricular output did not increase with cooling, and blood flow to most organs did not change significantly; however, blood flow to the skin decreased markedly, particularly in the lower body.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Glands↗

PubMed1993

Carotid, not aortic, chemoreceptors mediate the fetal cardiovascular response to acute hypoxemia in lambs.

The fetal cardiovascular response to acute hypoxemia consists of a decrease in heart rate, a variable change in mean arterial pressure, and an increase in peripheral vascular resistance. This response is mediated by the arterial chemoreceptors. To determine whether chemoreceptors in the carotid artery or in the aorta mediate the fetal cardiovascular response to acute hypoxemia, we studied the response to acute hypoxemia in fetal lambs at 125 to 130 d of gestation after selective carotid (six fetuses) or aortic (five fetuses) denervation. One to 3 d after insertion of catheters, hypoxemia was induced by inflating a balloon occluder around the ewe's hypogastric artery or by giving the ewe 95% N2 and 5% O2 to breathe. The chemoreflex response was measured as decrease in heart rate per decrease in Hb O2 saturation. To validate our results, we also studied the response to chemical stimulation of the chemoreceptors by injection of sodium cyanide into the inferior vena cava. We found that carotid denervation abolished the heart rate and peripheral vascular resistance responses to hypoxemia but that aortic denervation did not. Responses after injection of sodium cyanide were similar to those seen during acute hypoxemia. We conclude that the carotid chemoreceptors, and not the aortic chemoreceptors, mediate the fetal cardiovascular response to acute hypoxemia.

Animals↗

PubMed1993

Heart rate fall during acute hypoxemia: a measure of chemoreceptor response in fetal sheep.

The peripheral arterial chemoreceptor response to hypoxemia in the fetus is predominantly cardiovascular, invoking a fall in heart rate and a variable change in blood pressure. No quantifiable measure of chemoreceptor activity has yet been described in the intact fetus. We described the course, quantified the overall response, and defined the reproducibility of the heart rate response to acute hypoxemia in 22 late-term unanesthetized fetal sheep. Fetuses were chronically instrumented and studied between 1-6 days postoperatively. Acute hypoxemia was induced by occluding a balloon cuff around the common hypogastric artery. We performed 151 occlusions, starting at an initial saturation of 66 +/- 11%, decreasing saturation by 8-50%. Soon after balloon inflation, arterial oxygen saturation fell, followed by a decrease in heart rate. We calculated delta HR/delta sat, the fall in heart rate divided by the fall in saturation. Multiple linear regression analysis showed a sensitive chemoreflex, delta HR/delta sat averaging 2.5 +/- 1.2 bpm.%saturation-1. Initial saturation did not alter the first phase of the response (from the onset of the decrease in oxygen saturation to the onset of the decrease in oxygen saturation to the onset of the decrease in heart rate), but it did increase the overall response (delta HR/delta sat) when saturation was less than 65%. After adjusting in the lower range of initial saturations to that predicted at 65%, delta HR/delta sat was very reproducible within animals, with intra-animal variance being only 7% of inter-animal variance.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

PubMed1993

Significance of animal studies for perinatal research.

Only recently has it been possible to access human fetuses to obtain blood samples in utero, and to monitor circulatory dynamics by ultrasound. Most of our knowledge of fetal physiology and metabolism has been derived from animal studies. Using techniques of chronic implantation of intravascular catheters and specialized methods for measuring organ blood flow, cardiac output, and vascular pressures, much has been learned about normal fetal vascular physiology and its responses to stress. In addition, it has been possible to simulate abnormal morphology and to examine its effects on fetal function. Caution should be exercised in directly relating information obtained from animal studies to the human fetus. Differences in maturity at the time of birth, and in morphology, such as relative brain to body weight, must be taken into consideration.

Animals↗

PubMed1992

Effect of maternal oxygen administration on fetal oxygenation during graded reduction of umbilical or uterine blood flow in fetal sheep.

OBJECTIVE: Effects of maternal oxygen administration on fetal blood gases and on oxygen delivery and consumption during reduced uterine and reduced umbilical blood flows were examined. STUDY DESIGN: In eight pregnant sheep (gestational age 133 +/- 4 days) flow transducers were applied to a uterine and the common umbilical artery. Graded reductions in uterine and umbilical blood flows were achieved by a hypogastric artery snare and a balloon cuff encircling the umbilical cord. Fetal femoral arterial and umbilical venous oxygen contents and flows were measured at varying flow reductions with the ewe breathing air or oxygen. RESULTS: During 75% reduction in umbilical blood flow maternal oxygen administration significantly increased fetal oxygen delivery (6.4 +/- 2.5 to 7.7 +/- 2.3 ml/min/kg) and oxygen consumption (4.3 +/- 1.2 to 5.0 +/- 0.8 ml/min/kg). With similar reduction of uterine flow oxygen administration increased oxygen delivery from 8.3 +/- 2.4 to 12.3 +/- 3.6 and oxygen consumption from 3.3 +/- 0.8 to 4.7 +/- 1.6 ml/min/kg. CONCLUSION: Maternal oxygen inhalation improves fetal oxygenation during umbilical but especially during uterine blood flow reduction.

Animals↗

PubMed1992

Chemoreceptor responsiveness in fetal sheep.

Fetal peripheral chemoreceptor responses to arterial O2 saturation and changes in PCO2 have not yet been quantitated. In 24 late-term chronically instrumented fetal sheep, we measured the heart rate response to acute hypoxemia induced by uterine arterial occlusion at various resting O2 saturations (25-86%) and at induced reductions and increases in baseline O2 saturation. As an index of fetal chemoreceptor responsiveness we calculated the fall in heart rate divided by the fall in arterial O2 saturation (delta HR/delta sat). delta HR/delta sat was inversely related to resting O2 saturation at levels less than 65%, but greater than 65% this relationship was no longer present. However, an induced increase in baseline O2 saturation from 66 +/- 12 to 76 +/- 10% decreased delta HR/delta sat from 2.6 +/- 1.6 to 1.8 +/- 1.0, indicating that when resting O2 saturation is greater than 65% there may be adaptation of peripheral chemoreceptors. Below 65%, an induced decrease in baseline O2 saturation increased delta HR/delta sat (to 3.8 +/- 1.8), suggesting a lack of adaptation to lower O2 saturations. Concomitant changes in PCO2, or differences in baseline PCO2, did not affect delta HR/delta sat during uterine arterial occlusion, which suggests that there is no interdependence between O2 and CO2 as a stimulus for the fetal peripheral chemoreceptor. However, acute hypercapnia (n = 24 in 8 fetal sheep) induced bradycardia. Furthermore, this bradycardia was related to the increase in fetal arterial PCO2. We conclude that the fetal peripheral chemoreceptor is sensitive to hypoxemia and hypercapnia and that the hypoxemia response is accentuated with decreases in initial O2 saturation.

Acute Disease↗

PubMed1992

Effects of thyroid hormone on myocardial adrenergic beta-receptor responsiveness and function during late gestation.

To assess the effect of fetal hypothyroidism during late gestation on postnatal cardiovascular responsiveness, we measured heart rate and cardiac output responses to isoproterenol in newborn lambs. To evaluate the effect of such altered thyroid status on the development of beta-adrenergic signaling cascade, we measured myocardial beta-adrenergic receptor concentration and affinity, guanine nucleotide regulatory protein density, and adenylyl cyclase responsiveness. Twenty fetal lambs underwent either thyroidectomy and line placement or line placement alone at 128-130 d gestation. Five thyroidectomized and six control newborns were treated with isoproterenol, five thyroidectomized and four control newborns were killed upon delivery and tissue was obtained for biochemical studies, and four additional animals were delivered and killed at 126 d gestation and tissue was obtained for receptor analysis. Of the newborns treated with isoproterenol, the thyroidectomized lambs showed lower increase in heart rate and cardiac output compared with euthyroid newborns. Compared with the myocardium of normal newborns of similar gestation, the myocardium of the newborns who underwent fetal thyroidectomy failed to show the normal increase in beta-adrenoceptors accompanied by reduction in beta-adrenergic-stimulated adenylate cyclase activity. These results suggest that near term, the normal development of ovine fetus myocardial beta-adrenergic receptor is affected by thyroid hormones.

Adenylyl Cyclases↗

PubMed1991

Evaluation of changes in umbilical blood flow in the fetal lamb by Doppler waveform analysis.

Doppler velocity waveform analysis from descending aortic and umbilical artery signals was performed in 14 instrumented fetal lambs when umbilical blood flow was altered acutely. Blood flow was increased and reduced (by cord occlusion or placental embolization) and ranged 14% to 168% and 8% to 132% from baseline values in the descending aorta and the umbilical artery, respectively. When flow was severely reduced (less than 50% of baseline value), mean placental resistance increased almost fourfold and mean heart rate fell by 30% from baseline levels. There were only weak correlations between Doppler waveform indices and actual flow, which were usually not significantly different from the correlations between Doppler indices and actual heart rate. With both cord occlusion and placental embolization, significant changes of index values from baseline values were seen only when flow was severely reduced. We conclude that Doppler waveform analysis is not sensitive enough to detect acute mild to moderate reductions in placental flow. Increased index values with severely reduced flow may be explained in part by the concomitant fall in heart rate.

Animals↗

PubMed1991

Umbilical and hepatic venous responses to circulating vasoconstrictive hormones in fetal lamb.

Acute fetal hypoxemia increases the vascular resistance of the umbilical veins as well as that of the liver. Because, at least in the human, the umbilical-placental circulation has no autonomic innervation, circulating hormones could well be responsible for this increase in umbilical-placental outflow resistance. In chronically instrumented fetal sheep, norepinephrine, epinephrine, vasopressin, and angiotensin II were infused in sequentially increasing doses into the descending aorta and vascular resistance to umbilical-placental blood flow was measured. Norepinephrine and epinephrine increased the vascular resistance of the umbilical veins in a dose-dependent manner. Both catecholamines also increased the vascular resistance of the liver, resulting in an increase in ductus venosus blood flow. In contrast, vasopressin and angiotensin II had no effect on umbilical-placental outflow resistance. Thus catecholamines may be responsible for the increase in the vascular resistance of the umbilical veins and liver in response to acute fetal hypoxemia.

Angiotensin II↗

PubMed1991

Vascular responses of umbilical-placental circulation to vasodilators in fetal lambs.

It has been suggested that the umbilical-placental circulation is maximally vasodilated under normal conditions. To test this hypothesis, we investigated the effect of vasodilators on umbilical-placental vascular resistance. In nine chronically instrumented fetal lambs, catheters were placed in the descending aorta, umbilical artery, umbilical vein, and inferior vena cava. Umbilical-placental blood flow was measured by an electromagnetic flow probe placed around the common umbilical artery. Forskolin and nitroglycerin both dilated the umbilical-placental circulation, causing a dose-dependent decrease in umbilical-placental resistance to approximately 80% of baseline, indicating that the umbilical-placental circulation has some dilatory reserve. Both the adenosine 3',5'-cyclic monophosphate and the guanosine 3',5'-cyclic monophosphate mechanisms, which are directly stimulated by forskolin and nitroglycerin, respectively, are functional in the umbilical-placental circulation. However, the vasodilators prostacyclin and adenosine, which act through specific cell membrane receptors, have no effect on the umbilical-placental resistance. The inability of these agents to dilate the umbilical-placental circulation could be due to a lack of the appropriate receptors in the umbilical-placental vasculature.

Adenosine↗

PubMed1991

Doppler echocardiographic assessment of fetal descending aortic and umbilical blood flows. Validation studies in fetal lambs.

BACKGROUND: Doppler ultrasound has been used to assess abdominal aortic and umbilical blood flows in the human fetus, but the accuracy of this approach has not been demonstrated in an animal model. METHODS AND RESULTS: We compared abdominal aortic and umbilical blood flows determined by Doppler echocardiography in 12 fetal lambs with invasive flow measurements using radionuclide-labeled microspheres and electromagnetic flow transducers. We varied fetal blood flow from 100 to 950 ml/min in the abdominal aorta and from 130 to 610 ml/min in the umbilical vein. Invasive and Doppler echocardiographic flow measurements correlated well at both sites (y = 68 + 1.02x, r = 0.94, and y = 33 + 1.1x, r = 0.91, respectively). A slight overestimation of flow using the Doppler method may require a correction factor to assess actual flow. The degree of overestimation was not systematically related to measurements taken in smaller vessels or at larger angles of incidence. CONCLUSIONS: The present study demonstrates that determination of abdominal aortic and umbilical venous flows by echocardiography and pulsed Doppler ultrasound is feasible. Doppler measurements appear to be suited to serial comparison of actual flow.

Animals↗

PubMed1991

Effects of ductus venosus obstruction on liver and regional blood flows in the fetal lamb.

The ductus venosus allows highly oxygenated blood returning from the umbilical-placental circulation to bypass the liver, and is believed thereby to facilitate preferential distribution of this blood to the fetal brain and heart. To examine this hypothesis, we developed a model that allows acute obstruction of the ductus venosus in chronically catheterized fetal lambs. In seven fetal lambs, a Swann-Ganz catheter was inserted into the inferior vena cava and the balloon tip advanced into the ductus venosus. Control measurements were obtained 1-2 d after surgery, before and during inflation of the balloon in the ductus venosus. At each sample time, radioactive microspheres were injected to determine organ blood flow and the distribution of umbilical venous blood flow. During balloon inflation, the percentage of umbilical venous return passing through the ductus venosus was reduced from 38 +/- 15% to 1 +/- 0.5%. Umbilical-placental blood flow was unchanged from control values of 181 +/- 33 mL/min/kg. Total liver blood flow increased from 346 +/- 98 to 553 +/- 105 mL/min/100 g. Pressure in the inferior vena cava did not change, but umbilical venous pressure increased from 7.2 +/- 2.7 to 8.7 +/- 3.5 mm Hg. Total vascular resistance across the liver and ductus venosus increased from 0.013 +/- 0.006 to 0.020 +/- 0.011 during ductus venosus obstruction. Fetal heart rate, arterial blood pressure, and descending aortic pH and blood gases were unchanged, as was oxygen content in the descending aorta and carotid artery. Organ blood flows, combined ventricular output, and oxygen delivery were also unchanged. In five animals, these studies were repeated during maternal hypoxemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

In utero ventilation augments the left ventricular response to isoproterenol and volume loading in fetal sheep.

In its normal circulatory environment, the fetal left ventricle can maximally increase output less than 2-fold, in contrast to the nearly 3-fold increase that occurs at birth. Several studies have attributed this finding to fetal myocardial "immaturity," and speculated that there is a rapid maturation of the myocardium in the perinatal period. We investigated the importance of the circulatory environment itself, rather than myocardial immaturity, by measuring left ventricular output (LVO) during in utero oxygen ventilation and isoproterenol infusion. We studied seven near-term fetal sheep greater than or equal to 2 d after placement of intravascular catheters, an endotracheal tube, and an electromagnetic flow transducer around the ascending aorta. We measured hemodynamic variables in the presence and absence of all combinations of oxygen ventilation, isoproterenol infusion, and volume infusion. Baseline LVO was normal (133 +/- 27 mL.kg-1.min-1). Individually, oxygen ventilation (136 +/- 11 mL.kg-1.min-1, p less than 0.001) and isoproterenol (48 +/- 11 mL.kg-1.min-1, p less than 0.05) increased LVO significantly; volume infusion did not. Their cumulative effect increased LVO nearly 3-fold (to 387 +/- 98 mL.kg-1.min-1), similar to levels seen in the newborn lamb. Mean left atrial pressure increased above right during oxygen ventilation (from 0.05 +/- 0.54 kPa to 0.82 +/- 0.39 kPa, p less than or equal to 0.0001). We conclude that the previously observed limitation in maximal LVO in the near-term fetus is primarily caused by its circulatory environment rather than relative myocardial immaturity, and speculate that a prominent Starling response is uncovered by decreases in left ventricular afterload and right ventricular constraint.

Animals↗

PubMed1991

Effect of birth-related events on metabolism in fetal sheep.

At birth, changes in utilization of metabolic substrates occur as the fetus, dependent upon carbohydrates and amino acids available continuously from the placenta, becomes a neonate, dependent primarily upon fat obtained intermittently by suckling. In addition to changes in substrates, at birth, metabolic rate increases dramatically as the activity of several organs and thermoregulatory mechanisms increase. To determine whether metabolic changes are related to certain events that occur at birth, we studied 15 fetal sheep instrumented chronically with vascular catheters and an endotracheal tube at 133 to 137 d gestational age. We measured blood flow with radionuclide-labeled microspheres and arteriovenous concentration differences for oxygen content, blood glucose, and lactate across the placental, cerebral, myocardial, and hindlimb circulations at rest, during in utero ventilation of the fetal lungs with 3% O2, during in utero ventilation with 100% O2, and during ventilation with 100% O2 and umbilical cord occlusion. Ventilation with 3% O2 decreased oxygen uptake by the fetus and by the cerebral circulation but produced no other significant changes. Ventilation with the low and high oxygen gas mixture reduced glucose uptake by the fetus from the placental circulation dramatically to zero. In contrast, blood glucose concentrations increased and glucose uptake by the fetal brain, heart, and hindlimb were not altered significantly. These data indicate that, for a short time at least, complete cessation of glucose supply to the fetus from the placenta is not associated with decreases in blood glucose concentrations or utilization of glucose by a major portion of the fetal body.

Animals↗

PubMed1991

Cardiovascular responses to hypoxemia in sinoaortic-denervated fetal sheep.

Fetal cardiovascular response to acute hypoxemia is characterized by bradycardia, hypertension, and redistribution of cardiac output. The role of aortic and carotid chemoreceptors in mediating these responses was examined in eight sinoaortic-denervated and nine shamoperated fetal lambs. Blood gases, pH, heart rate, arterial pressure, and blood flow distribution were determined before and during hypoxemia. In intact fetuses, heart rate fell from 184 +/- 12 to 165 +/- 23 beats/min (p less than 0.01) but increased from 184 +/- 22 to 200 +/- 16 beats/min (p less than 0.05) in the sinoaortic-denervated fetuses. Intact fetuses showed an early hypertensive response to hypoxemia, whereas the sinoaortic-denervated fetuses developed a delayed, progressive rise in blood pressure. In both groups, fetal cardiac output and umbilical blood flow were maintained; cerebral, myocardial, and adrenal blood flow increased, and pulmonary blood flow decreased. Peripheral blood flow decreased 39% (p less than 0.001) in intact fetuses but was maintained in sinoaortic-denervated fetuses. Vascular responses to hypoxia in the brain, heart, adrenal, and lungs are regulated primarily by direct local effects. During hypoxemia, peripheral chemoreceptors mediate bradycardia and peripheral vasoconstriction but do not appear to be crucial for immediate fetal survival.

Animals↗

PubMed1991

Hemodynamic responses to alpha-adrenergic blockade during hypoxemia in the fetal lamb.

The mechanisms responsible for the increase in umbilical venous and hepatic vascular resistance during hypoxemia are poorly understood. To assess the relative importance of alpha-adrenergic receptors, we produced an acute, severe hypoxemia in chronically instrumented fetal sheep. While fetal arterial oxygen saturation was maintained at the same level, we then injected phentolamine, a selective alpha-adrenoreceptor blocker. We found that the hypoxemia-induced vasoconstriction of the umbilical veins and hepatic vasculature was reversed by alpha blockade. Thus, alpha-adrenergic stimulation is necessary to maintain vasoconstriction of the umbilical veins and hepatic vasculature during acute fetal hypoxemia. Furthermore, alpha-adrenergic stimulation is responsible for the hypoxemia-induced vasoconstriction of the gut, spleen, and lower carcass. Thus, the alpha-adrenergic system mediates important fetal hemodynamic adaptations to acute hypoxemia. However, the alpha-adrenergic system is not responsible for the hypoxemia-induced constriction of the renal vasculature.

Adrenergic alpha-Antagonists↗