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Biomedical subjects

A M Rudolph

Publications and source records attributed to A M Rudolph.

At least 127 records · Page 7Linked to original sources
PubMed1983

Maturation of circulatory responses to methionine-enkephalin.

The cardiovascular and respiratory effects of the naturally occurring endogenous opiate, methionine-enkephalin, were studied in 23 fetal sheep, five newborn lambs, 15 pregnant sheep, and four nonpregnant ewes. The opiate peptide produced dose-dependent decreases in heart rate and blood pressure in fetal and neonatal lambs but increased heart rate and blood pressure followed immediately by decreased heart rate and blood pressure in pregnant ewes. The circulatory responses were examined by pharmacologic blockade of receptor activity and by vagotomy. The bradycardia and hypotension in the fetus and tachycardia and hypertension in the adult were shown to be mediated by autonomic efferent nerves. Sinoaortic denervation did not affect the fetal responses to infused enkephalin. Respiration decreased in fetal as well as postnatal animals even at doses of methionine-enkephalin that did not significantly affect heart rate and blood pressure. These data indicate that the cardiovascular effects of infused enkephalins undergo maturational changes and are mediated by the autonomic nervous system.

Aging↗
PubMed1983

Effects of ambient temperature on oxygen consumption and the circulation in newborn lambs at rest and during hypoxemia.

To assess the effects of environmental temperature on responses to hypoxemia, we studied five unsedated lambs in the first week after birth. We catheterized the carotid artery and pulmonary artery (via the jugular vein). After recovery of at least 1 day, we measured pH, blood gases, arterial and mixed venous blood O2 content, oxygen consumption (VO2), heart rate, carotid and pulmonary arterial pressures, and cardiac output in both warm (25 degrees C) and cool (17.4 +/- 1.1 degree C) environments. In the cool environment, with no shivering, VO2 increased 40% (14.9 to 20.8 ml/kg/min). There were also increases of arteriovenous blood O2 content difference of 19%, cardiac output of 18%, and heart rate of 14%. In four lambs, we studied the same variables during hypoxemia (FiO2 = 0.09 for 1 h) at both temperatures. In the cool environment, hypoxemia produced a greater fall of VO2 (26% versus 6%) and arteriovenous oxygen differences (30% versus 19%) and a smaller increase of cardiac output (8% versus 14%) and heart rate (26% versus 43%). Also in the cool environment, core temperature decreased more (2.1 versus 0.4 degree C), but base deficit was the same (-6 versus -5 mEq/liter). Despite the greater fall in VO2 during hypoxemia in the cool environment, the lowest value achieved was still higher than the level during normoxemia in the warm environment. Similarly, cardiac output during hypoxemia was greater in the cool than in the warm environment. These findings may explain the variability in reported normal resting values and responses to hypoxemia. Contrary to previous reports, they also indicate that during severe hypoxemia neonates have a decreased reserve of metabolic and cardiovascular responses in a cool compared with a warm environment.

Animals↗
PubMed1983

Cardiovascular responses to alpha-melanocyte stimulating hormone during the perinatal period in sheep.

To determine the effects of alpha-melanocyte stimulating hormone (alpha MSH) on the circulation of undisturbed fetal sheep and young lambs and to explore possible mechanisms of actions, we examined the responses of ascending aortic blood flow, heart rate, stroke volume, and arterial blood pressure to a single intravenous injection of alpha MSH, ACTH, cortisol and to alpha MSH after beta-adrenergic blockade. We also measured cardiac output and organ blood flows before and after alpha MSH injection by the radionuclide labeled microsphere technique. alpha MSH increased ascending aortic blood flow from 249 +/- 23 to 327 +/- 30 ml X min-1 X kg-1 (P less than 0.001), heart rate from 111 +/- 10 to 126 +/- 11 min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-day-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and min-1, (P less than 0.001) and stroke volume from 2.32 +/- 0.21 to 2.75 +/- 0.20 ml X kg-1, (P less than 0.001) in 10 young lambs 15-30-days-old. alpha MSH decreased mean systemic arterial blood pressure from 42.6 +/- 1.7 to 39.3 +/- 1.6 mmHg (P less than 0.001) in fetal sheep and from 77.5 +/- 4.5 to 72.7 +/- 4.3 mmHg (P less than 0.001) in young lambs. In six additional young lambs (20-35-day-old) cardiac output, measured by microspheres, increased with alpha MSH from 216 +/- 20 to 261 +/- 19 ml X min-1 X kg-1 (P less than 0.001). alpha MSH also increased blood flow to the myocardium from 104 +/- 22 to 151 +/- 26 ml X min-1 X 100 g-1 (P less than 0.001), to the adrenals from 195 +/- 38 to 243 +/- 41 ml X min-1 X 100 g-1, (P less than 0.05), and to the lungs from 157 +/- 31 to 468 +/- 81 ml X min-1 X 100 g-1 (P less than 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗
PubMed1983

Negative feedback regulation of adrenocorticotropin secretion by cortisol in ovine fetuses.

The purpose of this study was to test the hypothesis that physiological increases in the fetal plasma cortisol concentration inhibit fetal ACTH responses to stress. Fetal sheep, between 121 and 131 days gestation, were infused with cortisol (4 micrograms/min) or vehicle for 5 h. One hour after the end of the cortisol or vehicle infusion, fetuses were infused with sodium nitroprusside (100 micrograms/min) to stimulate fetal ACTH and adrenal corticosteroid secretion. Cortisol, but not vehicle, elevated fetal plasma cortisol and suppressed the fetal ACTH and cortisol responses to nitroprusside. Cortisol and 11-deoxycortisol concentrations were significantly correlated in fetal plasma samples drawn during experiments in which cortisol was not infused; however, the cortisol to 11-deoxycortisol ratio was significantly increased during the infusion of nitroprusside. Fetal heart rate increased during vehicle infusion and decreased during cortisol infusion. Fetal blood pressure was not altered by either cortisol or vehicle infusion. Cortisol infusion increased fetal blood hemoglobin concentration, decreased maternal blood hemoglobin concentration, and produced metabolic acidosis in both mother and fetus. Vehicle infusion did not alter either fetal or maternal hemoglobin or pH. The data do not suggest an obvious mechanism for the cortisol-induced changes in fetal and maternal pH and hemoglobin or in fetal heart rate. However, some of the changes might be attributable to changes in fetal sympathetic outflow or to fluid shifts. We conclude that physiological increases in fetal plasma cortisol concentration: 1) inhibit subsequent ACTH responses to stress and 2) alter fetal cardiovascular function.

Adrenocorticotropic Hormone↗
PubMed1982

Effects of naloxone on fetal circulatory responses to hypoxemia.

The effects of opiate receptor antagonism on the fetal cardiovascular response to hypoxemia were examined by means of the radionuclide-labeled microsphere technique. Heart rate, blood pressure, and cardiac output were measured during baseline periods, during hypoxemia, and before and after infusion of either naloxone (1 mg/kg) or an equivalent volume of 0.0% saline solution. Seventeen fetal sheep were subjected to maternal hypoxemia by allowing the ewes to breathe 10% oxygen (3% carbon dioxide, 87% nitrogen). The fetuses responded with bradycardia (p less than 0.002 compared with control), increased blood pressure (p less than 0.002 compared with control), and no significant change in combined ventricular output or placental blood flow. After naloxone, the bradycardia increased by 10% (p less than 0.001), and both combined ventricular output and placental blood flow fell by 20% (p less than 0.01 and p less than 0.01, respectively). The fetal bradycardic response to naloxone was reversible with atropine. In fetuses with normal oxygenation of the blood (normoxemic), naloxone had no significant effect on heart rate and blood pressure. These data indicate that endogenous opiates (e.g., endorphin and enkephalin) are important in regulating the fetal circulation during hypoxia, and that the effects of opiate receptor antagonism may be mediated through the autonomic nervous system.

Animals↗
PubMed1982

The mechanism of late deceleration of the heart rate and its relationship to oxygenation in normoxemic and chronically hypoxemic fetal lambs.

The responses of fetal heart rate and blood pressure to a transient reduction in uterine blood flow were studied in normoxemic and chronically hypoxemic lambs. In normoxemic fetuses, a reduction in uterine blood flow, if prolonged sufficiently, produced reflex bradycardia mediated through chemoreceptors and was associated with a decrease in carotid arterial PO2 to below 20 torr. The bradycardia was associated with a marked decrease in left ventricular output as measured by electromagnetic flowmeter; both were abolished by atropine. In chronically hypoxemic fetuses, a reduction in uterine blood flow produced a delayed deceleration of the heart rate which consisted of three components: reflex bradycardia due to chemoreceptor stimulation; baroreceptor-mediated reflex bradycardia which involved the slow and late recovery of the heart rate; and nonreflex bradycardia which was probably secondary to hypoxic myocardial depression. Quantitative analysis revealed a relationship between the components of delayed deceleration and the status of fetal oxygenation prior to the reduction in uterine blood flow. The lower the carotid arterial PO2, the shorter was the delay in the onset of bradycardia, the greater the decrease in heart rate, and the more prolonged the duration of bradycardia. The conclusion is that the response of fetal heart rate to a transient reduction in uterine blood flow is related to the duration of the reduction and to the status of fetal oxygenation prior to the decrease in uterine blood flow.

Animals↗
PubMed1982

Hormonal and hemodynamic responses to vena caval obstruction in fetal sheep.

To test the hypothesis that ACTH and vasopressin responses are quantifiable as functions of induced changes in central venous or arterial pressures, we produced various degrees of vena caval obstruction in fetal sheep (118--134 days gestation). In seven experiments, vena caval obstruction increased heart rate 18 +/- 7 beats/min and carotid arterial oxygen saturation 8.4 +/- 2.1%, but did not alter any measured vascular pressure or hormones. More severe vena caval obstruction (n = 10) decreased mean arterial pressure 13 +/- 2 mmHg, central venous pressure 1.3 +/- 0.3 mmHg, and heart rate 47 +/- 12 beats/min, and increased fetal plasma ACTH 1,047 +/- 448 pg/ml, cortisol 4.4 +/- 2.2 ng/ml, and vasopressin 47.9 +/- 24.2 pg/ml, but did not alter 11-deoxycortisol. The stimulus increased plasma cortisol (radioimmunoassay after chromatography) 100% and "corticosteroids" (radiotransinassay without chromatography) 20%, demonstrating the nonlinear relationship between these two variables. End-inflation plasma ACTH and vasopressin concentrations were significantly related to the induced decreases in mean arterial and central venous pressures, suggesting that the hormonal responses to vena caval obstruction were mediated by cardiovascular mechanoreceptors. Plasma vasopressin concentrations were linearly related to plasma ACTH concentrations (4 = 0.94; P less than 0.001), suggesting parallel release of the two hormones.

Adrenal Cortex Hormones↗
PubMed1982

Effects of hemorrhage on umbilical venous return and oxygen delivery in fetal lambs.

The effect of acute hemorrhage (21.7 +/- 1.6%, mean +/- SE of the estimated blood volume) on the distribution of the umbilical venous return (UVR) and oxygen delivery to fetal organs (radionuclide microsphere technique) was studied in 10 chronically catheterized fetal lambs. Hemorrhage decreased UVR and total oxygen delivery to the fetus by 23 and 28%, respectively (P less than 0.001). A greater proportion of the UVR bypassed the liver through the ductus venosus (DV) (P less than 0.01). Consequently, DV blood flow was relatively maintained, and liver blood flow and oxygen delivery derived from the UVR decreased by 41 and 45%, respectively (P less than 0.002). The proportion of cardiac output constituted by DV blood increased by 30% (P less than 0.01). The changes in the distribution of the DV blood were similar to the changes in the distribution of cardiac output. As a result the proportion of organ blood flow and oxygen delivery derived from DV blood increased by 30% in both the upper and lower body organs. These studies show that fetal hemorrhage has a marked effect on the distribution of the UVR to the liver. The preferential distribution of the DV blood to the heart and brain is maintained but not enhanced. Our results indicate that changes in distribution of the DV-derived blood and oxygen following fetal hemorrhage is determined primarily by the responses of the arterial circulation, i.e., circulatory afterload.

Animals↗
PubMed1982

Fetal myocardial oxygen and carbohydrate consumption during acutely induced hypoxemia.

Two days after catheter placement we measured the heart rate, arterial blood pressure, myocardial blood flow, and the myocardial consumption of oxygen, glucose, lactate, and pyruvate in 11 fetal sheep in utero. We then administered 8-10% oxygen to the ewe, producing a 50% decrease in oxygen content in the fetal ascending aortic blood. After 15 min of hypoxemia we repeated the measurements. Oxygen content in the fetal coronary sinus blood decreased significantly, but the arteriovenous difference of oxygen across the left ventricle also decreased during hypoxemia. Fetal myocardial blood flow increased 160% above the control level, and the myocardial oxygen consumption did not change. The systolic arterial blood pressure increased and the heart rate decreased, but cardiac work, as estimated by the rate-pressure product, was unchanged. As both fetal myocardial oxygen consumption and cardiac work did not change, myocardial oxygenation, the relationship between oxygen consumption and cardiac work, appears to be unchanged during this degree of hypoxemia. Although arterial blood glucose, lactate, and pyruvate concentrations increased significantly during hypoxemia, only the myocardial consumption of pyruvate increased; the arteriovenous difference of glucose and lactate decreased in proportion to the increase in myocardial blood flow. During hypoxemia, glucose consumption did not change, and lactate continued to be consumed rather than produced; thus it is apparent that fetal myocardial metabolism continued to be aerobic during this degree of hypoxemia. Complete oxidative combustion of the quantities of carbohydrates that were consumed would supply all of the substrate necessary to meet fetal myocardial energy demands both at rest and during hypoxemia.

Animals↗
PubMed1982

Denervation of arterial chemoreceptors and baroreceptors in fetal lambs in utero.

Arterial baroreceptors and chemoreceptors were denervated in eight fetal lambs in utero. Carotid sinus and carotid body denervation was accomplished by stripping the carotid artery rostral and caudal to the origin of the occipital and lingual arteries. Aortic bodies were denervated by section of the superior laryngeal nerve and aortic nerve in the neck. The anatomy relevant to the technique is presented. The effectiveness of the denervation was tested by injection of 20 micrograms phenylephrine. The slowing of the fetal heart rate normally present in the intact lambs was abolished in the denervated fetuses. Denervation of the carotid and aortic chemoreceptors abolished the reflex bradycardia following injection of 200 micrograms cyanide or following acute hypoxemia produced by uterine blood flow reduction for 20 s. These results indicate that the baroreflex and chemoreflex can be elicited in utero and eliminated by the method we described. The preparation we present allows the study of the role of the arterial chemoreceptors and baroreceptors in normal fetal cardiovascular regulation and in fetal responses to stress.

Animals↗
PubMed1982

Regional myocardial blood flow and oxygen delivery in fetal, newborn, and adult sheep.

We measured and calculated their product, regional myocardial oxygen delivery, in unanesthetized, previously instrumented fetal, newborn, and adult sheep. In the fetus, blood flow and oxygen delivery were greater to the right ventricular free wall than to the left ventricular free wall. In the left ventricular free wall oxygen delivery increased significantly after birth and later decreased to a level in the adult that was similar to that of the fetus. There was a progressive decrease in oxygen delivery to the right ventricular free wall during the developmental period that we studied. Although the inner-to-outer blood flow ratio was significantly lower for the left and right ventricular free walls of the fetuses as compared with the newborns and adults, the ratio was greater than one in all three groups for both of the ventricular free walls. These data demonstrate that the changes that occur in the circulation after birth are associated with significant alterations in right and left ventricular myocardial blood flow and oxygen delivery, which most likely reflect changes in regional myocardial metabolic demands. In addition, there are further significant changes in regional myocardial blood flow during the transition from the newborn to adult hemodynamics.

Aging↗
PubMed1982

Relationship between peripheral blood flow and blood temperatures in lambs during hypoxemia and hemorrhage.

The relationships between the peripheral blood flow and arterial and venous blood temperatures were examined in 5 lambs (mean weight 10.5 kg, 4-12 weeks old) during hypoxemia and hemorrhage. Blood flow to one hind limb was measured continuously with an electromagnetic flow transducer around the femoral artery. Aortic and venous blood temperatures were monitored by means of thermistor catheters in the descending aorta and iliac vein. The intravascular catheters and flow transducer were implanted chronically and all studies were performed in conscious lambs, resting quietly. Skin temperatures were recorded at the hip and at the foot. The total heat in the hind limb (Htot), the net heat transported by circulating blood (Hbl), and the metabolic heat produced in the hind limb were calculated. The arterial and venous blood temperature were related to peripheral blood flow. When the flow was constant over a control period, blood temperatures remained constant. Hypoxemia, produced by administering a low oxygen gas mixture to the lamb, did not alter femoral blood flow, nor did it affect vascular temperatures. During hemorrhage, femoral blood flow fell, arterial temperature rose by 0.46 degrees C and venous temperature by 0.85 degrees C; arteriovenous temperature difference decreased from 0.85 to 0.44 degrees C. There was an inverse relationship between femoral blood flow and venous temperature in each individual lamb subjected to hemorrhage, with a correlation of 0.91. For each 10-ml/min decrease in peripheral blood flow the venous temperature rose an average of 0.33 degrees C. Changes in peripheral blood flow were immediately reflected by changes in the venous temperature.

Animals↗
PubMed1982

Comparison of methods of measuring cardiac output in newborn lambs.

To define agreement between methods, we measured cardiac output (CO) in chronically instrumented lambs by four different methods. In 23 lambs we measured CO simultaneously by the Fick and microsphere methods and with an electromagnetic flowmeter over a wide range of CO (80-454 ml/kg/min) in different experimental conditions on 97 occasions. When the electromagnetic flowmeter was corrected for coronary flow (about 8% of CO) calculated from microspheres, the mean cardiac outputs were almost identical for these three methods (237, 235, and 236 ml/kg x min, respectively). Comparisons between any two of the methods showed a correlation coefficient greater than 0.89. In four lambs, 52 measurements of CO by Fick and thermodilution had a correlation coefficient of 0.94. We conclude that any of the four methods, if appropriately applied, adequately measures CO in a variety of circumstances and may be used with confidence for physiologic or other studies.

Animals↗
PubMed1982

Recovery of cardiovascular function in newborn lambs after thoracotomy.

Knowledge of the quality and speed of recovery after thoracotomy is crucial for studies of the early changes in cardiovascular function in the neonatal period. We studied the early recovery period after thoracotomy with pericardiotomy, but without ventriculotomy, in 21 lambs operated on between 2-24 days after birth. In 15 lambs, we measured resting pH,, PaO2, PaCO2, O2 consumption, cardiac output, heart rate, and aortic and pulmonary arterial pressures, before and after thoracotomy, daily for 1 wk. We found that, except for PaO2 (82 versus 87 torr), all variables returned to normal by the third day after thoracotomy. Four lambs were exposed to hypoxia (FIO2 0.09 for 1 h) before and 3 days after thoracotomy; hypoxia-induced changes were not different at the two different periods. Six other lambs, undergoing thoracotomy within the first 3 days after birth and exposed to hypoxia on the third postoperative day, had hypoxia-induced responses similar to six age-matched nonthoracotomized lambs. These findings indicate recovery of cardiovascular function by 48-72 h after thoracotomy. We believe, therefore, that reliable studies of the circulation in lambs are possible as early as 3-4 days after birth, even if thoracotomy is required for making measurements.

Age Factors↗
PubMed1981

Selective distribution of microspheres injected into the umbilical veins and inferior venae cavae of fetal sheep.

To investigate the extent of streaming of umbilical venous blood in the venous and arterial circulations of normal and hypoxic sheep fetuses and to experimentally determine its effect on determinations of blood flow by means of the microsphere method, we injected 15 mu microspheres labeled with different radionuclides into the umbilical veins (UVs) and distal inferior venae cavae (DIVC) of 21 chronically catheterized near-term sheep fetuses. We determined the ratio of the radioactive counts from the UV-injected microspheres to the radioactive counts from the DIVC-injected microspheres (UV/DIVC count ratio) in each fetal tissue in 40 experiments. In 75% of the normal fetuses and 58% of the hypoxic fetuses, UV-injected microspheres streamed preferentially through the foramen ovale to the left atrium and ventricle when compared with DIVC-injected microspheres. Fetal hypoxia was associated with a significant decrease in the extent of preferential streaming. In the arterial circulation, we found no evidence for preferential streaming of UV-injected and DIVC-injected microspheres.

Animals↗