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Biomedical subjects

L D Longo

Publications and source records attributed to L D Longo.

At least 19 recordsLinked to original sources
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↗
PubMed1989

Errors in microsphere determination of cardiac output: a computer simulation in fetal sheep.

Through use of a compartmental model, we simulated the measurement of cardiac output and distribution by means of radioactively labeled microspheres in fetal lambs with weights between 0.5 and 3 kg. A systematic error in measured cardiac output caused by artifactual changes in blood volume caused by the injection and withdrawal of fluids during the procedure was less than 5% for fetal weights greater than or equal to 1 kg but increased for fetal weights less than 1 kg and when hypovolemia was simulated at all fetal weights. Sensitivity analysis disclosed no significant effect of changes in vascular resistance. We examined the effects of recirculation of microspheres and found no significant increase in error in the measured value of cardiac output due to 20% recirculation of all spheres entering a single isolated organ system; however, errors between 7 and 14% were observed with simulations of 20% recirculation in more than one compartment simultaneously. Recirculation also introduced significant errors in the measured distribution of cardiac output in certain cases. The effect on the measured cardiac output of a temporary change in the true cardiac output was dampened by the artifactual blood volume changes mentioned above and the fact that the measurement is a time-weighted average. We also evaluated four different experimental designs. We conclude that the microsphere technique provides a remarkably reliable means of quantifying cardiac output and individual organ flow in the fetus. The nonrandom errors inherent in the procedure examined in this study are of the order of 10%, which is likely to be less than the moment-to-moment variation in the true cardiac output.

Algorithms↗
PubMed1989

Cardiac function during long-term hypoxemia in fetal sheep.

To examine right ventricular function during long-term hypoxemia, we instrumented 12 fetal sheep with intravascular catheters and an electromagnetic flow probe on the pulmonary artery. In six cases, hypoxemia was induced by infusing N2 gas into the maternal trachea for 2 wk. Maternal arterial PO2 was less than 60 Torr, and fetal arterial PO2 was reduced from approximately 26 to approximately 19 Torr. Six cases served as nonhypoxic controls. We studied fetal cardiac function by increasing either preload with a volume infusion of 5% (wt/vol) dextrose or afterload by administering methoxamine (alpha-adrenergic agonist). In hypoxic animals, right ventricular output (QRV) and stroke volume (SV) were not affected on the first 2 days but fell 30% on day 3. Fetal arterial pressure (Pfa) increased 20%, hemoglobin concentration increased approximately 30%, and fetal heart rate (FHR) showed minimal changes. Within 2 wk, QRV recovered to normal values, whereas ventricular sensitivity to arterial pressure was reduced. We observed no change in plasma concentration of "cardiac enzymes" or differences in fetal growth between groups. In conclusion, during prolonged hypoxemia, right ventricular function showed a triphasic response (primary maintenance, secondary depression, and subsequent recovery), achieving a new steady state 2 wk after the start of hypoxia, characterized by decreased sensitivity to afterload, associated with polycythemia and hypertension.

Animals↗
PubMed1989

Maternal responses to long-term hypoxemia in sheep.

To determine the maternal cardiovascular responses to long-term hypoxemia, we studied three groups of animals: 1) pregnant ewes (n = 20) at 110-115 days gestation subjected to hypoxia for up to 28 days; 2) pregnant ewes (n = 4) that served as normoxic controls; and 3) nonpregnant ewes (n = 6) subjected to hypoxemia for up to 28 days. We measured mean arterial pressure, heart rate, uterine blood flow, and uterine vascular resistance continuously for 1 h/day while the ewe was exposed to an inspired O2 fraction of 12-13% for at least 17 days. Arterial PO2, O2 saturation, hemoglobin, arteriovenous O2 difference, and uterine O2 uptake were measured daily while blood volume and erythropoietin concentration were measured weekly. In the pregnant hypoxic group arterial PO2 decreased from a control value of 101.5 +/- 5.1 to 59.2 +/- 5.1 Torr within a few minutes, where it remained throughout the study. The hemoglobin concentration increased from 8.9 +/- 0.5 to 10.0 +/- 0.5 g/dl within 24 h where it remained, whereas erythropoietin concentration increased from 16.6 +/- 2.1 to 39.1 +/- 7.8 mU/ml at 24 h but then returned to near-control levels. Arterial glucose concentration, mean arterial pressure, and cardiac output decreased slightly but insignificantly. In contrast, body weight, heart rate, blood volume, uterine blood flow, uterine O2 flow, uteroplacental O2 uptake, and the concentrations of catecholamines and cortisol remained relatively constant. Thus both pregnant and nonpregnant sheep experience relatively minor cardiovascular and hematologic responses in response to long-term hypoxemia of moderate severity.

Animals↗
PubMed1989

Fetal responses to long-term hypoxemia in sheep.

The effect of acute or short-term hypoxia on fetal cardiovascular hemodynamics has been well known; however, little is known about the effect of long-term hypoxemia. To determine the fetal hemodynamic responses to this stress we studied two groups of animals: 1) pregnant ewes (n = 20) at 110-115 days of gestation subjected to hypoxia for up to 28 days and 2) pregnant ewes (n = 4) that served as normoxic controls. We chronically catheterized the fetal brachiocephalic artery and vein. Five to 6 days after surgery, control measurements were made of mean arterial blood pressure, heart rate, arterial PO2, O2 saturation, hemoglobin, hematocrit, blood volume, and the concentrations of erythropoietin, cortisol, epinephrine, and norepinephrine. The next day the ewes were placed in a chamber with an inspired O2 fraction of 12-13%. Within a few minutes fetal arterial PO2 decreased from control value of 29.7 +/- 2.1 to 19.1 +/- 2.1 Torr, where it remained. Hemoglobin increased from 10.0 +/- 1.0 to 12.9 +/- 1.9 g/dl by day 7, where it remained. This was associated with an increase of erythropoietin from 22.8 +/- 2.2 to 144 +/- 37 mU/ml within 24 h, but by day 7 it had returned to levels slightly above normal. Epinephrine also increased moderately and remained elevated throughout the study. However, values of mean arterial pressure and heart rate did not differ from controls. Perhaps surprisingly, these fetuses were able to compensate so that at term their body weights were normal, 3.77 +/- 0.2 kg.

Animals↗