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Biomedical subjects

K C Lowe

Publications and source records attributed to K C Lowe.

At least 91 records · Page 5Linked to original sources

Lymphoid tissue responses to perfluorocarbon emulsion in mice.

The effects of either intraperitoneal or intravenous injection of low doses (5 or 10 ml/kg) of the proprietary emulsified perfluorocarbon-based blood substitute, Fluosol-DA 20%, on mouse lymphoid tissue and antibody production against sheep erythrocytes (SRBC) have been investigated. Mean liver weight was significantly increased and gut mesenteric lymph node (MLN) weights decreased in all animals injected with Fluosol-DA, irrespective of route of administration. In contrast, spleen weight decreased following intravenous injection of emulsion at 5 ml/kg. The mean plasma haemagglutination response to SRBC was significantly (P less than 0.01) increased in animals injected intraperitoneally with Fluosol at both doses but was similar to control in all other cases. These results show that lymphoid tissue responses to Fluosol-DA in mice are variable and that antibody production against intraperitoneally-injected SRBC is enhanced by prior injection of emulsion into the peritoneal cavity.

Animals↗

Lymphoid tissue responses to a novel perfluorochemical emulsion in rats.

The effects of a novel perfluorochemical emulsion on rat lymphoid tissues and antibody production against sheep red blood cells (SRBC) have been studied. The responses were compared with those following injection of identical doses of the proprietary emulsion, Fluosol-DA 20% (F-DA). Liver weight was increased up to 15% at 8 days following intravenous (i.v.) or intraperitoneal (i.p.) injection of the novel emulsion but was unaffected by F-DA injection. Spleen weight also increased by a maximum of 20% in response to i.p. injection of the novel emulsion but this was less than increases of up to 44% which occurred in F-DA-injected rats. Thymus weight decreased (P less than 0.05) following i.p. injection of the novel emulsion whereas mesenteric lymph node (MLN) weight remained unchanged. However, MLN weight was increased in response to i.v. injected F-DA, while thymus weight showed a small increase following i.p. F-DA injection. Mean plasma antibody titres to SRBC were significantly (P less than 0.01) increased at 7 days after immunization in rats pretreated with i.p. injections of either the novel emulsion or F-DA; titres in animals pretreated with i.v. injections of either emulsion were similar to control.

Animals↗

Changes in plasma enzyme concentrations in response to blood substitution with perfluorocarbon emulsion in the conscious rat.

The effects of near total blood replacement with the proprietary perfluorocarbon (PFC)-based emulsion, Fluosol-DA 20%, on plasma concentrations of 2 enzymes, lactate dehydrogeanse (LDH) and alkaline phosphatase (ALP), have been examined in conscious, chronically catheterized rats. A pronounced fall in both plasma LDH (p less than 0.05) an ALP (p less than 0.01) occurred in response to exchange-transfusion. However, at 6 h following blood replacement, plasma concentrations of both enzymes had risen to values significantly greater than those measured immediately before perfusion. The observed changes in plasma LDH and ALP after blood replacement with Fluosol-DA indicated alterations in normal functioning of tissues from which these enzymes originate.

Alkaline Phosphatase↗

Plasma growth hormone concentration in the chronically catheterized ovine fetus during spontaneous term delivery and premature delivery induced by continuous intravascular infusion of low doses of adrenocorticotropin or cortisol to the fetus.

Fetal plasma growth hormone concentrations were measured in 15 pregnant ewes over the last 5 days before delivery. In five chronically catheterized pregnant ewes that underwent spontaneous vaginal delivery 146 +/- 2 days (mean +/- SD) of gestation, fetal plasma growth hormone concentrations fell from 124.6 +/- 44.1 ng X ml-1 5 days before delivery to 35.2 +/- 31.3 ng X ml-1 at delivery. In three fetuses in which premature delivery was induced by the infusion of cortisol to the fetus at 128 days of gestation, fetal plasma growth hormone levels fell from 195 +/- 19.1 ng X ml-1 to 70.7 +/- 25.5 ng X ml-1 over the last 5 days of intrauterine life. In seven fetuses in which premature delivery was induced with infusion of synthetic adrenocorticotropin to the fetus beginning at 120 or 130 days of gestation, the fetal plasma growth hormone level did not fall (175.6 +/- 75.7 to 158.9 +/- 60.1 ng X ml-1). Fetal plasma cortisol concentrations at delivery were significantly higher in the cortisol-infused fetuses (214 +/- 38.4 ng X ml-1) than in both control (94.4 +/- 33.7 ng X ml-1) and adrenocorticotropic hormone-infused fetuses (94.5 +/- 31.9 ng X ml-1). The fall in the fetal plasma growth hormone level in cortisol-induced fetuses may be due to the higher fetal plasma cortisol concentrations achieved in the cortisol-infused compared with the adrenocorticotropic hormone-infused fetuses in which no comparable decrease in growth hormone was observed. These findings suggest that there are significant differences in the fetal response to various experimental regimens used for the induction of premature labor in the sheep.

Adrenocorticotropic Hormone↗

Effects of a perfluorocarbon emulsion, Fluosol-DA, on rat lymphoid tissue and immunological competence.

The effects of administration of low doses (5 or 10 ml/kg body wt) of the proprietary perfluorocarbon emulsion blood substitute, Fluosol-DA 20%, on rat lymphoid tissue and antibody production against sheep red blood cells (SRBC) have been studied. Spleen and mesenteric lymph nodes (MLN) were significantly heavier at eight days after injection of Fluosol, whereas liver and thymus weights were unchanged. The mean plasma antibody titre to sheep red blood cells was significantly (P less than 0.05) increased in animals injected intraperitoneally with both doses of Fluosol-DA before immunization. These results show that there are differences in the uptake of perfluorochemicals by certain rat lymphoid tissues and that immunological competence can be altered following administration of such materials.

Animals↗

Blood transfusion or blood substitution?

Blood transfusion has become a universally accepted, life-saving procedure in modern clinical medicine. In addition, specific blood fractions are widely used in the therapeutic treatment of haematological disorders. Problems are, however, encountered in conventional transfusion practice and in the clinical use of blood components. This paper outlines some of those problems and considers how plasma expanders and oxygen-carrying blood substitutes may be used to overcome some of them. The extent to which acceptable blood substitutes have been developed and tested in both animal and human studies is especially emphasized.

Blood Substitutes↗

Changes in intravascular fluid composition following blood replacement with perfluorocarbon emulsion in the rat.

The effects of near total blood replacement with the proprietary perfluorocarbon emulsion, Fluosol-DA, have been examined in conscious, chronically catheterized rats. Animals survived for up to 48 h with a haematocrit of less than 2%. No overt changes in cardiovascular or respiratory functions occurred during blood replacement but thereafter, animals showed a progressive deterioration of haemodynamic control. Changes in intravascular fluid composition during and following exchange-transfusion have been monitored and the extent to which these changes could have contributed to the eventual disruption of homeostasis is discussed.

Animals↗

Comparison of changes in ovine plasma chorionic somatomammotropin concentrations in the fetus and mother before spontaneous vaginal delivery at term and adrenocorticotropin-induced premature delivery.

Fetal and maternal plasma ovine chorionic somatomammotropin concentrations have been measured in eight pregnant ewes immediately prior to spontaneous vaginal delivery at 146 +/- 2 gestational days. In seven additional ewes, fetal and maternal plasma ovine chorionic somatomammotropin concentrations were measured immediately before and during induction of premature delivery by infusion of 1 microgram X hr-1 synthetic adrenocorticotropin (ACTH1-24) to the fetus commencing at either 120 to 122 gestational days (n = 3) or 130 to 132 gestational days (n = 4). Both fetal and maternal plasma ovine chorionic somatomammotropin concentrations fell significantly (p less than 0.05) in the 5 days before spontaneous term delivery; no change in the fetal to maternal ratio for plasma ovine chorionic somatomammotropin concentrations was observed. In contrast, the maternal plasma ovine chorionic somatomammotropin concentration rose (p less than 0.05) during infusion of ACTH1-24 to the fetus while the fetal concentration declined. During infusion of ACTH1-24 to the fetus the fetal to maternal ratio for plasma ovine chorionic somatomammotropin concentrations also fell. The finding that the parallel fall in ovine plasma ovine chorionic somatomammotropin concentrations in the fetus and mother in spontaneous term deliveries is not seen following ACTH-induced premature delivery suggests that mechanisms other than activation of the fetal adrenal axis induce the prepartum fall in ovine chorionic somatomammotropin secretion. These findings militate against a role for the fall in ovine chorionic somatomammotropin in the initiation of parturition.

Adrenocorticotropic Hormone↗

The effects of xylazine on uterine activity, fetal and maternal oxygenation, cardiovascular function, and fetal breathing.

Various pharmacologic agents used in the experimental study of physiologic processes may have pronounced effects on the systems under study. We have studied the effects of xylazine (Rompun) on myometrial activity, fetal and maternal pH, blood gases, heart rate, and fetal breathing movements in chronically catheterized fetal sheep. Xylazine is widely used as a premedication for various forms of animal operations, including the instrumentation of the chronically catheterized fetal sheep preparation. Animals were studied on postoperative day 5. Xylazine had pronounced effects on maternal PaO2 and heart rate that lasted for at least 3 hours. Fetal heart rate and PaO2 returned to preinjection levels within 60 minutes. Myometrial activity doubled in the first 60 minutes after administration of xylazine and did not return to preinjection levels for 3 hours. Fetal diaphragmatic electromyographic activity was almost completely absent in the first and second hours, with a return to normal within 4 hours. These changes were absent in the saline solution-injected control animals. The observed changes in uterine activity and fetal breathing may have been direct effects of xylazine itself or the result of increased uterine activity. The different duration of changes in the ewe and fetus suggests a compensatory mechanism at the uteroplacental level or in the fetoplacental unit.

Animals↗

Acute responses during blood substitution in the conscious rat.

Changes in the cellular components of blood in response to exchange transfusion with the fluorocarbon emulsion blood substitute Fluosol-DA 20% have been examined in conscious chronically catheterized rats. Continuous isovolemic exchange transfusion at 1 ml X min-1 for 40 min reduced the mean haematocrit from 36% to less than 2%. The animals behaved normally during blood replacement and no significant changes in mean arterial blood pressure, heart rate or respiration rate were observed. An exponential decline in circulating red and total white cell count was observed during exchange transfusion. However, the rates of decline were significantly different for red and white cells as was reflected in the half-times (t1/2) for the decrease in cell numbers (red blood cells: 7.5 min; white blood cells: 27.5 min) and the fractional turnover rates (k). An exponential decline in total plasma protein and plasma albumin concentrations occurred in response to blood substitution with highly significant inverse log-linear relationships with time and with closely similar half-times (t1/2) for the decrease in concentration (total protein: 10.5 min; albumin: 11.3 min) and the fractional turnover rates (k). If a single well-mixed compartment is assumed for each type of blood cell and plasma proteins, the differences in turnover rates can be attributed to the volumes of these compartments (red blood cells: 10.9 ml.; white blood cells: 40.0 ml.; total protein: 15.2 ml.; albumin: 16.4 ml.). Possible anatomical boundaries for these compartments are considered. Plasma sodium concentration showed a significant decrease in response to blood substitution; no corresponding changes in either plasma potassium or total plasma calcium concentrations were observed. A progressive rise in plasma glucose concentration occurred during blood substitution, with levels at the end of the experiment approximately 2-fold higher than the mean initial value. There was also a small but not statistically significant decrease in plasma urea concentration during the procedure.

Animals↗

Fetal and adult hemoglobin in the chronically catheterized sheep fetus.

The switch from fetal to adult hemoglobin (Hb) has been investigated in fetal and newborn lambs. In the period between 125 and 145 days gestation, the proportion of fetal cells containing adult Hb increased significantly in catheterized fetuses. This increase paralleled the rise in fetal plasma cortisol under several different experimental conditions. However, infusion of synthetic adrenocorticotropin (ACTH1-24) into the fetus, which increased fetal plasma cortisol concentrations to levels slightly higher than observed at term, did not bring about any increase in the proportion of cells containing adult Hb. Increasing fetal plasma prolactin (PRL) concentration either by infusion of PRL or by stimulating endogenous PRL release with thyrotropin-releasing hormone (TRH) did not influence the time or rate of the switch. The fetal reticulocyte count was significantly higher in blood samples taken at the time of catheterization in fetuses of 103-115 days gestation than at 116-128 days gestation. In one repeatedly sampled fetus of adult type Hb AB, Hb C was observed at the time when the fetus was anemic. At birth the number of cells containing adult Hb was significantly higher in catheterized lambs than in nonoperated controls.

Animals↗

Changing patterns of steroid production in the fetus and placenta and their effects on development.

A variety of radioimmunoassays specifically characterized for use with fetal and maternal ovine plasma have been used to measure steroid hormone concentrations in small plasma samples drawn simultaneously from mother and fetus. By repeated sampling from the same animal preparation the changes over time of plasma concentrations of cortisol, pregnenolone and its sulphate, and oestrone and oestrone sulphate have been systematically studied. In animals delivering spontaneously at term the fetal plasma cortisol concentration rises between 120 and 130 days gestation and plays an important part in the maturation of several vital physiological systems, including the fetal thyroid axis. In normal term deliveries and premature deliveries induced by synthetic adrenocorticotropin (ACTH(1-24), 1 microgram h-1), the concentration of oestrone sulphate in maternal plasma increases before the fetal plasma concentration. Fetal and maternal oestrogens are probably important in the control of the low-grade tonic myometrial activity that occurs throughout gestation, in the initiation of labour and in the control of uterine blood flow. Low-grade tonic myometrial activity affects fetal oxygenation, fetal breathing and the fetal sleep state and may constitute a pathway through which the mother influences fetal development, with important physiological and possibly pathological consequences.

Adrenal Glands↗