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Biomedical subjects

L D Longo

Publications and source records attributed to L D Longo.

At least 73 records · Page 4Linked to original sources
PubMed1993

Changes in ovine fetal adrenocortical responsiveness after long-term hypoxemia.

This study tested the hypothesis that in the fetus long-term hypoxemia induces premature adrenocortical maturation and augments adrenal responsiveness to adrenocorticotropin hormone (ACTH). Pregnant ewes were exposed to high altitude (3,820 m) from 30 to 120 days gestation, when surgery was performed. Maternal arterial pressure of O2 (PaO2) was maintained at approximately 60 Torr by N2 infusion through a tracheal catheter. Fetal PaO2 was significantly lower in the hypoxemic (21 +/- 0.2 Torr) vs. normoxic (26 +/- 0.4 Torr) fetuses (P < 0.01). Between 125 and 140 days, basal ACTH and cortisol concentrations were similar in both groups. To assess changes in adrenal responsiveness, we challenged the fetuses with ACTH (100 ng/kg body wt, iv bolus) at 126 and 136 days. At 126 days, after ACTH challenge, fetal plasma ACTH peaked at similar values (275 +/- 43 and 250 +/- 26 pg/ml) in normoxic and hypoxemic fetuses, respectively. Plasma cortisol subsequently increased to 84 +/- 8 and 44 +/- 6 ng/ml in these groups. At 136 days, after ACTH challenge, plasma ACTH peaked at 379 +/- 57 and 336 +/- 21 pg/ml in normoxic and hypoxemic fetuses, respectively. Although plasma cortisol concentration in normoxic fetuses increased to 180 +/- 21 ng/ml, levels in hypoxemic fetuses only reached 62 +/- 12 ng/ml (P < 0.05 compared with normoxic). Catecholamine concentrations were not significantly different between the two groups. These data do not support the hypothesis that adrenocortical maturation occurs prematurely, augmenting adrenal responsiveness to ACTH after exposure to long-term hypoxemia. Rather, the ability of the fetus to respond to an ACTH challenge is blunted.

Adrenal Cortex↗
PubMed1993

Cerebrovascular adaptations to high-altitude hypoxemia in fetal and adult sheep.

In the fetus and infant, high-altitude hypoxemia is associated with increased cerebrovascular morbidity. To test the hypothesis that this increased morbidity involves changes in cerebrovascular endothelial and smooth muscle function, we examined middle cerebral, posterior communicating, basilar, and common carotid arteries obtained from 23 normoxic fetuses, 19 hypoxemic fetuses maintained at high altitude (3,820 m) from 30 days gestation to near term (approximately 143 days), 55 normoxic non-pregnant adults, and 24 hypoxemic nonpregnant adults maintained at the same altitude and duration as the hypoxemic fetuses. Long-term hypoxemia was associated with several significant changes in both fetal and adult arteries, including a generalized increase in base-soluble protein (5-50%), a depression of the maximum potassium-induced tensions (16-49%), and a depression of the relaxation responses to S-nitroso-N-acetylpenicillamine (1-11%), which releases nitric oxide into solution upon hydration. Altitude acclimatization significantly enhanced amine-to-potassium ratios (the ratio of tension produced by 10 microM serotonin with 20 microM histamine to that produced by 122 mM potassium) only in adult cerebral arteries (51-87%) and significantly depressed potassium-induced stresses (up to 41%) and serotonin/histamine-induced tensions (20-37%) only in fetuses. Endothelium-dependent relaxations to A23187 were significantly depressed in hypoxemic fetuses (4-11%) but were significantly enhanced in hypoxemic adults (2-14%). We conclude that chronic hypoxemia depresses both vascular smooth muscle and endothelial function to a greater extent in fetal than in adult cerebral arteries and that this effect could contribute to the greater postnatal vulnerability to asphyxic and hypertensive insults seen in hypoxemic neonates.

Acclimatization↗
PubMed1993

Fibroblast growth factor enhances the transcription and stability of human chorionic gonadotropin beta-subunit messenger ribonucleic acid in Jar choriocarcinoma cells.

In previous studies, we found that basic fibroblast growth factor (bFGF) significantly stimulated the secretion of hCG beta in the Jar choriocarcinoma cell line. In the present study, the effect of bFGF on the steady state hCG beta mRNA level in this cell line was determined. Application of Northern analyses with total RNA isolated from bFGF-stimulated Jar cells revealed that, in a time-dependent manner, the steady state hCG beta mRNA level increased progressively, reaching 4-fold of the control value within 4 h after exposure to bFGF. The observed accumulation was due in part to increased transcription (2.4-fold relative to that in control cultures), as determined by nuclear transcription studies. In addition, bFGF increased the stability of the hCG beta message; the message half-life was increased from approximately 3 h (in control cultures) to greater than 6 h (in bFGF-treated cultures). These data demonstrate that bFGF stimulates hCG beta mRNA accumulation in a complex manner regulated through both transcriptional and posttranscriptional mechanisms.

Actins↗
PubMed1992

Right and left ventricular function in fetal sheep exposed to long-term high-altitude hypoxemia.

To test the hypothesis that long-term hypoxemia affects fetal cardiac function, we measured right (RVO) and left (LVO) ventricular output by electromagnetic flow probes. We also determined their responses to increased preload (ventricular function curve, VFC) and afterload (arterial sensitivity curve, ASC). We exposed seven pregnant ewes to high altitude (3,820 m) from 30 to 120 days gestation, at which time surgery was performed. Thereafter, maternal arterial PO2 was maintained at approximately 60 Torr by N2 administration. Fetal arterial PO2 was significantly reduced in the hypoxemic fetuses (Hyp, n = 7) compared with that of control (Con, n = 9) (19.3 +/- 0.8 vs. 23.3 +/- 0.5 Torr, P less than 0.01). Mean arterial pressures in the Hyp group were elevated (52.0 +/- 1.2 vs. 44.4 +/- 1.7 mmHg, P less than 0.01) and fetal heart rate showed minimal change. Catecholamine concentrations in the Hyp group tended to be higher than the Con group, but not significantly so. For Con and Hyp, RVO equaled 275.7 +/- 9.1 vs. 183.1 +/- 10.1 (P less than 0.01), LVO equaled 165.7 +/- 16.9 vs. 141.6 +/- 16.5 (NS), and combined ventricular output (CVO) equaled 441.1 +/- 22.9 vs. 334.9 +/- 28.3 ml.min-1.kg-1 (P less than 0.05). For the LV there were no significant differences of the VFC between the Con and Hyp groups. However, the right VFC in the Hyp was significantly shifted downward. Concerning afterload, in the RV the slope of the ASC of Con was steeper than that of Hyp (-3.00 +/- 0.05 vs. -0.84 +/- 0.11 ml.ml.min-1.g-1.mmHg-1, P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Altitude↗
PubMed1992

Pregnancy-induced changes in ovine cerebral arteries.

We examined the effects of pregnancy on the ovine cerebral vasculature by comparing several characteristics of isolated endothelium-intact segments of three intracranial arteries including the middle cerebral (MCA), posterior communicating (PC), and basilar (BAS) arteries taken from pregnant sheep (138-143 days gestation, term approximately 145 days) and nonpregnant controls. For comparison, segments of the extracranial common carotid (COM) artery were also studied. With pregnancy, vessel water content increased (5.4-5.8%) in all arteries except the PC. Additionally, cellular protein content increased in all arteries (4.4-50.0%). Arterial stiffness, as determined by passive stress-strain determinations, was significantly decreased during pregnancy in the MCA but not in the larger arteries. Maximum contractile responses, when normalized to vessel wall cross-sectional area, were consistently greater in arteries from pregnant than in those from nonpregnant animals (10.1-49.7%). Relaxation to the endothelium-independent guanylate cyclase stimulator S-nitroso-N-acetyl penicillamine (SNAP) increased with pregnancy only in the distal MCA (approximately 17%). Endothelium-dependent relaxation to the calcium ionophore A23187 decreased only in the larger and more proximal COM (-39%). Thus pregnancy was associated with an increase in production of contractile force, a decrease in peripheral vascular stiffness, a decrease in the relaxant response to A23187 in the COM, and an increase in the relaxant response to SNAP in the MCA. Together, these findings indicate that pregnancy has widespread and important vessel specific cerebrovascular consequences that affect not only arterial composition, but also contractility and endothelial reactivity.

Analysis of Variance↗
PubMed1992

Dissociation of pulsatile cortisol and adrenocorticotropin secretion in fetal sheep during late gestation.

In the fetal sheep, plasma cortisol concentrations gradually increase in the last weeks of gestation and abruptly rise during the final 48-72 h preceding birth. To determine if these changes in mean circulating cortisol concentrations result from increased pulsatile secretion and are driven by changes in ACTH pulses, blood samples from five chronically catheterized fetuses were collected every 5 min for 2 h at 133 days gestation and every 4 days thereafter until delivery at 146 +/- 2 days. Volume was replaced after each blood sample and erythrocytes were returned every 20 min. Plasma cortisol and ACTH secretion were pulsatile in fetuses at all ages. Cortisol pulse frequency increased significantly with gestation from a mean of 2.2 pulses/2 h at 133 days to 4.8 pulses/2 h at 146 days. The interpulse interval (mean +/- SE) decreased between 133 and 146 days from 54 +/- 11 min to 23 +/- 3 min, respectively. Cortisol pulse amplitude increased significantly from 10 +/- 2 ng/ml at 133 days to 44 +/- 13 ng/ml at 146 days. In contrast to cortisol, ACTH pulse frequency (3 +/- 0.6 pulses/2 h) and amplitude (21 +/- 3 pg/ml) were similar at 133 days and 146 days. The coincidence of cortisol and ACTH pulses did not change between 133 and 146 days. Furthermore, the number of coincident pulses failed to exceed random associations (hypergeometric probability analysis) and could have occurred by chance alone (P values ranged from 0.11-0.63). A point by point comparison of cortisol and ACTH concentrations in fetal circulation indicate that only 36% of the variance in cortisol concentrations could be explained by variance in ACTH (cross-correlation analysis). These data suggest that fetal cortisol and ACTH secretion are pulsatile and that, as gestation advances, increases in constitutive cortisol pulse amplitude and frequency may not be predominantly driven by pulsatile changes in ACTH in the ovine fetal circulation near term.

Activity Cycles↗
PubMed1991

Developmental changes in ovine cerebral artery composition and reactivity.

We have examined age-related changes in segments of common carotid (Com), basilar (Bas), posterior communicating (PC), and middle cerebral (MC) arteries taken from 14 near-term fetal lambs, 62 newborn lambs 3-7 days old, and 42 adult nonpregnant sheep. Transition from fetal to newborn life was associated with a decreased water content in all arteries ranging from 0.6% (Com) to 2.3% (Bas), no change in the relative content of cellular protein, an increase in wall thickness ranging from 4% (MC) to 26% (Com), an increase in maximum contractile tension ranging from 18% (MC) to 82% (Com), an increase in stiffness, an increase in the maximum active stress ranging from 6% (Bas) to 43% (Com), a decrease in the amine-to-potassium ratio (calculated as the maximum response to 10 microM serotonin with 20 microM histamine divided by the maximum response to 122 mM K+) ranging from 8% (Bas) to 51% (Com), and a decrease in the norepinephrine-to-potassium ratio ranging from 2.1% (Bas) to 56% (Com). Thus developmental changes associated with the transition from fetal to newborn life were much more pronounced in the larger, more proximal Com than in the smaller, more distal cerebral arteries, suggesting that, at term, the cerebral arteries are more mature both functionally and structurally than the Com arteries. Similarly, the transition from newborn to adult life was associated with much greater changes in Com characteristics than with those of the cerebral arteries. These studies demonstrate that the effects of aging vary considerably along the cerebrovascular tree and that conclusions based on developmental studies of large systemic arteries cannot be freely extrapolated to the smaller arteries of the circle of Willis.

Aging↗
PubMed1991

Regulation of basal adrenocorticotropin and cortisol secretion by arginine vasopressin in the fetal sheep during late gestation.

This study tested the hypothesis that arginine vasopressin (AVP) is involved in the regulation of basal ACTH secretion in the ovine fetus near term. In five fetuses challenged with AVP (1 microgram/ml, iv bolus) plasma ACTH concentrations increased to an 8-fold peak within 10 min of the preceding baseline (55 +/- 6 to 403 +/- 241 pg/ml). Cortisol in fetal circulation subsequently increased 2-fold (11 +/- 1 to 28 +/- 5 ng/ml) within 15 min of the AVP injection. The AVP-induced rise in plasma ACTH and cortisol concentrations was blocked when the fetus was pretreated with the AVP V1 receptor antagonist d(Ch2)5Tyr(Me)AVP. In a total of seven studies, antagonist (10 micrograms/kg estimated BW, iv bolus) was administered to three fetuses, aged 137-147 days gestation, followed 40 min later by the exogenous AVP challenge, as described above. After AVP antagonist treatment, basal ACTH and cortisol concentrations were not significantly different from the preinjection baseline levels (P greater than 0.05, by analysis of variance). Moreover, plasma ACTH and cortisol remained unchanged after the AVP challenge. To further define the role of endogenous AVP in basal ACTH and cortisol secretion, the AVP antagonist was administered (five studies in two fetuses) at 30-min intervals for a total of three injections per fetus. This extended AVP antagonist regimen also failed to alter fetal circulating concentrations of ACTH or cortisol (P greater than 0.05). Cortisol in the maternal circulation was not affected by any of the fetal AVP or AVP antagonist treatments. Lambs were born at 146 +/- 2 days gestation (n = 5), within the range for the normal duration of pregnancy. These data do not support the hypotheses that AVP is involved in the regulation of basal ACTH secretion in the fetal sheep during the 10 days preceding parturition. Rather, the ability of AVP antagonist to block the AVP-induced rise in plasma ACTH and cortisol in the fetus suggests that basal and stimulated ACTH secretion are under separate regulatory mechanisms.

Adrenal Glands↗
PubMed1991

Developmental aspects of endothelial function.

We believe that the mechanisms through which nitric oxide and guanylate cyclase produce relaxation are fully functional in cerebral arteries at term in the fetal sheep and probably also in the term human infant. The relation between cGMP levels and the degree of relaxation varies both with age and with the relaxant used in a vessel specific manner. The factors underlying this variability constitute a fruitful area for future research and include possible age-related changes in membrane potential, calcium channel density and currents, and the participation of cGMP-independent mechanisms, to name only a few. Between fetal and newborn life, the biotransformation of nitroglycerin appears to improve significantly, particularly in the smaller more distal cerebral arteries. This improvement may be a clue to other important vascular metabolic and enzymatic changes that occur during the perinatal period. At the endothelial level, responses to A23187, an index of maximum endothelial vasodilator capacity, are relatively stable across the perinatal period and do not change consistently with age across all arteries. More importantly, large arteries, such as the common carotid, appear to relax better than the smaller cerebral arteries, and this difference is greater in fetal than in adult arteries. Responses to ADP disappear with age in the common carotid, but remain or even become enhanced in the cerebral arteries, thus illustrating the key role played by changes in receptor type and distribution in development and maturation.

Adenosine Diphosphate↗
PubMed1990

Harvey Cushing and pediatric neurosurgery.

Harvey Cushing made fundamental and seminal contributions to pediatric neurosurgery. Early in his surgical career, he described the diagnosis and treatment of subdural hematomas in newborn infants. Important investigations on the cerebrospinal fluid and the nature of hydrocephalus were carried out under his direction, first by Walter Dandy and Kenneth Blackfan in the Hunterian Laboratory at the Johns Hopkins School of Medicine, and shortly afterward by Lewis Weed at the Laboratory of Surgical Research at Harvard. Cushing's principle interest throughout his professional career was the surgical treatment of brain tumors. By his careful clinical examination of patients. Cushing described for the first time a typical and composite picture of the more common tumors of the posterior fossa in children, particularly the cerebellar astrocytomas and medulloblastomas. Percival Bailey, working under Cushing's supervision at Harvard, studied and classified the glioma group of brain tumors. This contribution by Bailey was a major factor in the understanding of the characteristics and natural history of these tumors. In the closing years of Cushing's surgical practice, he published three major papers summarizing the characteristics, clinical picture, and treatment of the more common brain tumors in the pediatric age group. As a result of his exceptional surgical skill and innovations, he was able to achieve a surgical mortality of only 4% in operations on brain tumors in children. These landmark papers secured Cushing's place as a pioneer in pediatric neurosurgery.

Animals↗
PubMed1990

Effects of hypoxia on contractility of isolated fetal lamb cerebral arteries.

We studied the contractile properties of isolated cerebral arteries in near term fetal lambs, as well as the magnitudes and rates of relaxation during moderate hypoxia. Paired 5-mm segments of basilar, middle cerebral, posterior communicating, and common carotid arteries were suspended in a temperature controlled bath and isometric tension measured during 122 mM K(+)-induced contractions. In one vessel of each pair hypoxia was imposed by switching the bubbling gas from 95% O2 + 5% CO2 to 95% N2 + 5% CO2 4 minutes into a K+ contraction, thus lowering the bath PO2 to approximately 15 Torr. After 15 min exposure to hypoxia the middle cerebral artery had relaxed 61%, the posterior communicating 46%, the basilar 44%, and the common carotid only 18% compared to normoxic controls. All cerebral arteries relaxed relatively rapidly (relaxation rates of 42-45 x 10(-4) s-1), whereas the common carotid relaxed slowly (20 x 10(-4) sec-1). The data indicate that these cerebral arteries play an important role in regulating blood flow responses during hypoxemia in intact fetuses.

Animals↗
PubMed1989

Lymph flow rate response to angiotensin II is decreased in pregnant sheep.

Pregnancy in humans is associated with a number of physiologic changes including interstitial fluid retention (edema) and a decrease in the systemic vascular response to infused angiotensin II. In nonpregnant sheep angiotensin II increases the lymph flow rate by what appears to be a direct effect on the lymphatic vessels. The purpose of this study was to test the hypothesis that during pregnancy the lymph flow rate response to angiotensin II infusion is decreased in relation to that of the nonpregnant state. We speculate that a decrease in lymph flow may explain the interstitial fluid retention observed during human pregnancy. In nine nonpregnant and five pregnant chronically catheterized ewes, we infused angiotensin II at rates of 0.1, 10, and 1000 ng/kg/min during a 5-minute period, with intervals of at least 15 minutes between doses. At the highest angiotensin II dose, peak lymph flow rate increased 286% in pregnant ewes compared with an increase of 344% in the nonpregnant sheep (p less than 0.05). No changes occurred in the intravascular volume, plasma or lymph protein concentration, or venous pressure. The arterial pressure responses to angiotensin II were decreased in pregnant sheep (p less than 0.05). These results are compatible with a model for fluid retention in pregnancy in which a decreased lymph flow rate plays a significant role in interstitial fluid retention.

Angiotensin II↗