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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 325 records · Page 18Linked to original sources
PubMed1985

Leakage of protein in the immature rabbit lung; effect of surfactant replacement.

Immature newborn rabbits, delivered on day 27 of gestation, were ventilated artificially for 60 min, with or without previous treatment with natural surfactant. Insufflation pressure was adjusted to maintain an average tidal volume of about 10 ml/kg. All animals received, before the onset of ventilation, 125I-labeled albumin via the airways and 131I-labeled albumin intravenously. At the end of the experiment 3.1 +/- 1.3% (means +/- SD) of the 131I-albumin had permeated into the alveolar compartment of control animals; the corresponding figures for surfactant-treated animals were 1.7 +/- 0.8% (P less than 0.002). In control animals only 18.2 +/- 4.4% of the 125I-albumin could be recovered from the airspaces after 60 min, whereas 69.9 +/- 14.6% of this label was recovered in surfactant-treated animals (P less than 0.002). Alveolar wash samples from control animals also contained significantly increased activity of surfactant inhibitor, as evaluated with pulsating bubble. The bidirectional flux of protein, including surfactant inhibitor, was thus significantly decreased in these immature lungs by surfactant replacement.

Albumins↗
PubMed1985

Lung protein leaks in ventilated lambs: effects of gestational age.

To study the protein permeability properties of the ventilated premature lung, we delivered groups of eight lambs at 122 and 135 days gestational age and ventilated the lambs equivalently. The lambs at 122 days gestational age had been treated with natural sheep surfactant at birth, and both groups of lambs had similar pH and blood gas values to 3 h of age. Three groups of lambs at 146 days gestational age also were studied for comparison; four lambs were ventilated to normalized PCO2 values, four lambs were ventilated equivalently to the premature lambs with supplemental CO2 used to normalize PCO2 values, and four lambs were treated with natural surfactant and ventilated similarly to the preterm lambs. The percent recovery into an alveolar wash and lung tissue of 131I-albumin given by intravascular injection and of 125I-albumin given into the airways was measured in each animal after killing at 3 h of age. Full-term lambs had a small bidirectional leak of albumin to and from the alveoli and lung tissue. The recovery of intravascular 131I-albumin in the alveolar wash was 5.8- and 4.1-fold higher in lambs at 122 and 135 days gestational age, respectively, than in full-term lambs. The loss of 125I-albumin from the airways and alveoli also increased as gestational age decreased. The bidirectional flux of albumin to and from the alveoli increased as gestational age decreased in the prematurely delivered and ventilated lambs.

Albumins↗
PubMed1985

Effects of high-frequency and conventional ventilation on the premature lamb lung.

Twelve sets of twin lambs were delivered prematurely by cesarean section at 133-136 days gestational age and ventilated for 3 h with either high-frequency oscillation (HFO) or conventional mechanical ventilation (CMV). Blood gases and pH values were monitored at 30-min intervals, and ventilator settings were adjusted to maintain CO2 partial pressure (PCO2) values within the normal range. There were no differences in the sequential blood gas or pH values between the HFO or CMV lambs. Mean airway pressures (MAP) between 8.0 and 20.4 cmH2O were required, indicating lung disease of variable severity in the lambs. The bidirectional protein leak from the vascular space to the airways and alveoli and vice versa was measured with radiolabeled albumins given by intravascular injection and with fetal lung fluid at birth. The albumin leaks in both directions increased as MAP required to normalize PCO2 increased, but the degree of leak was independent of type of ventilation. Pathological findings of epithelial necrosis and hyaline membranes occurred to a similar extent in lung sections from both groups of lambs. In the HFO animals less phosphatidylcholine in the alveolar wash and more of a tracer dose of radiolabeled natural surfactant that had been given at birth became tissue associated. These results indicate a decrease in the initial secretion of surfactant and/or a stimulation of reuptake in the HFO animals. HFO did not protect the immature lung from the development of large protein leaks or the pathological changes of the respiratory distress syndrome.

Animals↗
PubMed1985

Distribution of pulmonary blood flow in relation to atelectasis in premature ventilated lambs.

To investigate the ability of the preterm, ventilated lung to redirect blood flow away from atelectatic regions, we studied lambs with respiratory distress syndrome and spontaneous atelectasis or atelectasis caused by bronchial obstruction with a balloon catheter. Pulmonary blood flow distributions were measured by quantifying 15-mu, microsphere-associated radioactivity within multiple pieces of lung. Lambs with well aerated or very atelectatic lungs had relatively uniform blood flow/gram lung in all pieces of lung. Blood flow was much less uniform in lungs with both aerated and atelectatic regions. In 9 lambs with spontaneous atelectasis that included 25 +/- 5% (mean +/- SE) of the lungs by weight, blood flow was 29 +/- 4% less to atelectatic than to aerated lung volumes (p less than 0.01). In 5 lambs with well-aerated lungs, 18 +/- 3% of the lung by weight was made atelectatic by balloon occlusion of a major lower lobe bronchus. There was a 44 +/- 11% decrease in blood flow to the atelectatic lung segments. These studies document the ability of the lung of the premature, ventilated lamb to shunt pulmonary blood flow away from atelectatic lung volumes.

Animals↗
PubMed1985

Normalization of arterial blood gases after treatment of surfactant-deficient lambs with Tween 20.

Pulmonary surfactant (PS) is capable of lowering surface tension at an air-water interface to less than 10 dynes/cm. This property of PS is believed to be important for normal lung function. We tested the detergent Tween 20, which cannot lower surface tension at an air-water interface to less than 25 dynes/cm, for its ability to promote reasonable gas exchange in surfactant-deficient lambs delivered prematurely at 120 to 124 days gestation. Lambs were treated at birth with 75 mM NaCl (control), 5% Tween 20 in 75 mM NaCl, or PS in 75 mM NaCl and placed on infant ventilators. Control lambs had poor oxygenation and were in respiratory failure at 30 min of age (arterial PCO2 of 75.8 +/- 11 mmHg (mean +/- SE)) despite peak inspiratory pressures (PIP) of 32 +/- 0.7 cm H2O. Pulmonary surfactant treatment allowed adequate ventilation with a PIP of 23.8 +/- 1.2 cm H2O. Tween treatment also allowed adequate ventilation with a PIP of only 27 +/- 1.3 cm H2O. Minimal surface tensions in alveolar washes of control and Tween-treated lambs were 28.7 +/- 1.3 and 26.7 +/- 2.3 dynes/cm, respectively, compared with less than 10 dynes/cm for PS-treated lambs. Thus, Tween 20 did not alter the alveolar wash minimal surface tension when compared with that of the control animals but it did significantly improve gas exchange and lung compliance.

Animals↗
PubMed1985

The contractility and performance of the preterm left ventricle before and after early patent ductus arteriosus occlusion in surfactant-treated lambs.

The influence of left-right ductal shunting on early hemodynamic responses, namely left ventricular performance, contractility, and systemic perfusion was evaluated in nine preterm lambs (120 days gestational age) treated with surfactant. Blood gases were maintained in the physiological range using mechanical ventilation; hemodynamic and blood flow measurements (radionuclide labeled microspheres) were obtained before and after occlusion of the patent ductus arteriosus with a catheter balloon. The mean left-right ductal shunt before occlusion (1.2 h postnatal age) was 59 +/- 11% SD. Left ventricular output was increased in all lambs with PDA (pre: 306 +/- 106 versus post: 155 +/- 31 ml/min/kg; p less than 0.001); effective systemic blood flow and organ blood flows did not change. The left ventricle end-diastolic volume was increased in all and decreased following ductal occlusion (pre: 2.0 +/- 0.4 versus post: 1.5 +/- 0.2 ml/kg; p less than 0.01). Cardiac rate, ejection fraction, and contractility (peak dP/dt) did not change. Right-left ductal shunting was not detected in six similarly treated lambs. Thus, during the 1st h of life the hemodynamic profile of preterm lambs with patent ductus arteriosus was characterized by large magnitude left-right shunt and a "high" cardiac output state sufficient to maintain unchanged systemic perfusion. The increased left ventricle output was accomplished by increasing end-diastolic volume (Frank-Starling mechanism), but left ventricle contractility remained unchanged. We speculate that the preterm left ventricle may be unable to sustain the high level of pump performance and contractility required to compensate for the ductal "steal" of systemic blood flow.

Animals↗
PubMed1985

Accumulation of alveolar surfactant following delivery and ventilation of premature lambs.

We studied the accumulation of surfactant in the alveoli and airways from birth to 10 h of age in 60 lambs delivered prematurely at a mean gestational age of 136 days. The lambs were delivered by cesarean section and ventilated by varying peak inspiratory pressures only to normalize arterial blood gas and pH values. Alveolar surfactant accumulation was measured either by alveolar wash after timed sacrifice or by repetitive sampling of the airways using an isotope dilution technique. The fall in specific activity of phosphatidylcholine with time was measured after the intratracheal administration of either a trace dose of 3H-labeled natural surfactant and synthetic 14C-dipalmitoylphosphatidylcholine (DPPC) at birth or a treatment dose of the same mixture at 5 h of age (about 55 mg of total surfactant lipid/kg body weight). From the change in phosphatidylcholine-specific activities and the quantities and specific activities of phosphatidylcholine measured in alveolar washes, we found that the surfactant pool sizes as estimated by alveolar wash or by the isotope dilution technique were similar. The pool size of alveolar surfactant increased fourfold from birth to 20 min of age and doubled again by 10 h of age. The shape of the curve for the accumulation of alveolar surfactant versus time was independent of the final pool size achieved at 10 h of age. Sonicates of DPPC when mixed with either a trace amount or a treatment dose of natural surfactant were treated by the premature lung in a manner indistinguishable from the phosphatidylcholine associated with natural surfactant.

Animals↗
PubMed1985

Clearance of large amounts of natural surfactants and liposomes of dipalmitoylphosphatidylcholine from the lungs of rabbits.

Three-day-old rabbits were given intratracheal injections of radiolabeled natural sheep surfactant, rabbit surfactant, or liposomes of dipalmitoylphosphatidylcholine that contained greater than three times the quantity of phosphatidylcholine present in the endogenous surfactant pool. The recoveries of radiolabeled phosphatidylcholine and total phosphatidylcholine in alveolar washes, lung tissue, and total lung (alveolar washes plus lung tissue) were measured for 72 h. Approximately half of the two natural surfactants rapidly became lung tissue associated, and phosphatidylcholine derived from the rabbit surfactant was cleared from the total lung twice as rapidly as was the phosphatidylcholine from sheep surfactant (20.7% versus 10.4% of the amount present at zero time/24 h, p less than .05). The alveolar surfactant pool size did not decrease despite the clearance of the exogenously administered material. The liposomes of dipalmitoylphosphatidylcholine were cleared from the total lung at the same rate as the rabbit surfactant phosphatidylcholine; however, compared to the natural surfactants, much less of this material became lung tissue associated. The administration of the natural rabbit surfactant did not decrease the amount of radiolabeled choline, palmitic acid, or 32P that was incorporated into lung phosphatidylcholine or the amount of labeled phosphatidylcholine that was secreted to the alveoli. However, sheep surfactant increased the percent of radiolabeled phosphatidylcholine recovered by alveolar wash. These experiments document differences in clearance rates, tissue and alveolar association patterns, and subtle effects on endogenous surfactant metabolism for two surfactants and liposomes of dipalmitoylphosphatidylcholine following intratracheal administration. Uniform metabolic responses should not be anticipated following treatments with different surfactant preparations.

Animals↗
PubMed1984

Reutilization of phosphatidylcholine analogues by the pulmonary surfactant system. The lack of specificity.

Five specific 14C-labelled analogues of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, (L-alpha-DPPC) including 1-palmitoyl-sn-glycero-3-phosphocholine, (L-alpha-lysoPC) and 2,3-dipalmitoyl-sn-glycero-1-phosphocholine (the D isomer of DPPC) were individually mixed with L-alpha-[3H]DPPC and unlabelled natural surfactant isolated from 3-day-old rabbits. The mixtures were injected intratracheally into 3-day-old rabbits which were then killed at preset times up to 72 h after injection. Phosphatidylcholine was isolated from the alveolar wash and from lamellar body fraction from each rabbit and was analyzed for the ratio of 3H-to-14C counts/min. These ratios were plotted against the time the rabbits were killed to determine whether a difference existed in the rates of reutilization of the analogues relative to L-alpha-DPPC. By 60 h L-alpha-lysoPC was reutilized at 42% of the efficiency of the L-alpha-[3H]DPPC with which it was injected. That part of the L-alpha-lyso which was reutilized had been converted to [14C]phosphatidylcholine. Each of the other four analogues was reutilized by the surfactant system as efficiently as L-alpha-DPPC. These results are most consistent with a process of bulk uptake of surfactant from the alveolar space by the Type II cell with subsequent processing for resecretion which involves minimal specificity for molecular structure.

Animals↗
PubMed1984

Histopathological and immunohistochemical study of neuroendocrine tumors of the rectum.

A clinicopathological and immunohistochemical study was carried out on 32 cases of neuroendocrine tumors of the rectum. Typical carcinoids consisted of 27 cases, histologically showing uniform round to columnar cells forming solid alveolar nests and ribbon-like or trabecular arrangement. Neuroendocrine carcinomas consisted of 5 cases in which tumor cells with prominent nuclear atypism were arranged in a ribbon-like or trabecular fashion and formed gland-like structures. There were also small round tumor cells resembling lymphocytes. The prognosis of neuroendocrine carcinomas is very poor with marked tumor invasion of lymphatics and veins resulting in liver metastases and death within one year after operation. Thirty cases out of the 32 showed a positive argyrophil reaction, while immunohistochemistry of 29 cases revealed more than one peptide hormone in 23 cases. The most common hormone was somatostatin being present in 18 of the 23 tumors and glucagon in 16 of the 23 tumors. Gastrin/CCK and calcitonin were proven in 6 of the 23 tumors and in 4 of the 23 tumors, respectively. On the other hand, more than two hormones was present in 15 of the 23 tumors examined. Histologically, neuroendocrine tumors have a very wide spectrum. Histogenetically, typical carcinoids and neuroendocrine carcinomas are considered to be of the same origin with the former showing morphological and functional differentiation to endocrine cells and the latter being more undifferentiated.

Adult↗
PubMed1984

A protein from airways of premature lambs that inhibits surfactant function.

A protein that interfered with surfactant function was isolated from the alveolar washes of prematurely delivered and ventilated lambs. This inhibitor was recovered following sequential precipitation with polyethylene glycol, Affi-Gel Blue, and diethylaminoethyl (DEAE) cellulose chromatography as a protein of approximately 110,000 mol wt. Compared to surfactant alone or surfactant and bovine serum albumin, the purified inhibitor increased the time required for surfactant to spread, increased both maximal and minimal surface tensions, increased the percent surface area that had to be compressed to reach a minimum surface tension of less than 15 dyn/cm, and delayed the surface adsorption of surfactant. The effect of inhibitor on the minimum surface tensions of surfactant solutions was inversely related to surfactant concentration. A radioimmunoassay was used to estimate that approximately 10% of the protein from plasma of premature lambs and alveolar washes after 4 h of ventilation was inhibitory. Following the simultaneous intravascular injection of labeled inhibitor and bovine serum albumin, about 4% of the radioactivity associated with both proteins was recovered in alveolar washes and 6% was associated with lung tissue after alveolar wash. This large proportionate leakage of both proteins did not occur in other tissues. The inhibitor affected multiple measurements of surfactant function in vitro and its presence may contribute to a surfactant deficiency state in the immature lung.

Animals↗
PubMed1984

Surfactant and pulmonary blood flow distributions following treatment of premature lambs with natural surfactant.

Prematurely delivered lambs were treated with radiolabeled natural surfactant by either tracheal instillation at birth and before the onset of mechanical ventilation, or after 23 +/- 1 (+/- SE) min of mechanical ventilation. Right ventricular blood flow distributions, left ventricular outputs, and left-to-right ductal shunts were measured with radiolabeled microspheres. After sacrifice, the lungs of lambs receiving surfactant at birth inflated uniformly with constant distending pressure while the lungs of lambs treated after a period of ventilation had aerated, partially aerated, and atelectatic areas. All lungs were divided into pieces which were weighed and catalogued as to location. The amount of radiolabeled surfactant and microsphere-associated radioactivity in each piece of lung was quantified. Surfactant was relatively homogenously distributed to pieces of lung from lambs that were treated with surfactant at birth; 48% of lung pieces received amounts of surfactant within +/- 25% of the mean value. Surfactant was preferentially recovered from the aerated pieces of lungs of lambs treated after a period of mechanical ventilation, and the distribution of surfactant to these lungs was very nonhomogeneous. Right ventricular blood flow distributions to the lungs were quite homogeneous in both groups of lambs. However, in 8 of 12 lambs, pulmonary blood flow was preferentially directed away from those pieces of lung that received relatively large amounts of surfactant and toward pieces of lung that received less surfactant. This acute redirection of pulmonary blood flow distribution may result from the local changes in compliances within the lung following surfactant instillation.

Animals↗
PubMed1984

Lack of correlation of severity of lung disease with the phosphatidylcholine concentration in fetal lung fluid from premature lambs at 133-136 days gestational age.

Fetal lung fluid was collected following tracheotomy at the time of delivery of 40 premature lambs at 133-136 days gestational age. The concentration of phosphatidylcholine and saturated photophatidylcholine in fetal lung fluid was compared with the severity of lung disease of the lambs as assessed after 3 to 10 h of controlled mechanical ventilation with only peak inspiratory pressures varied to control the PCO2 values. Phosphatidylcholine concentration in fetal lung fluid did not correlate with the peak inspiratory pressures needed to ventilate the lambs, total lung compliance values, or the surfactant phosphatidylcholine pool sizes measured by alveolar wash after sacrifice. The ratio of saturated to total phosphatidylcholine was constant (0.55 +/- 0.02) and independent of concentration of phosphatidylcholine in the fetal lung fluid. The fetal lung fluid contained only about 0.7% of the final surfactant phosphatidylcholine pool released by the lambs to the alveoli after birth. Within a narrow gestational age range characterized by lung disease of widely varying severity, the phosphatidylcholine concentrations in fetal lung fluid were not predictive of the severity of lung disease.

Animals↗
PubMed1983

Route of incorporation of alveolar palmitate and choline into surfactant phosphatidylcholine in rabbits.

Intratracheal injection of 3-day-old rabbits with radioactively labeled palmitic acid and choline results in an 8-10-fold increase in the efficiency of their incorporation into surfactant phosphatidylcholine when compared to the intravenous injection of these precursors. Based on labeling patterns in microsomal, lamellar body and alveolar wash fractions, the incorporation appears to be via normal surfactant synthetic pathways. Intratracheal injection of phospholipid precursors is useful for producing relatively high specific activity natural surfactant.

Animals↗
PubMed1983

The significance of reutilization of surfactant phosphatidylcholine.

To assess the magnitude of reutilization of surfactant phosphatidylcholine, 68 3-day-old rabbits were injected intratracheally with a trace dose of [3H]choline-labeled surfactant mixed with [14C]palmitate-labeled synthetic dipalmitoylphosphatidylcholine. After timed kills we measured the total phosphatidylcholine associated counts/min in whole lung and alveolar wash and the specific activities of phosphatidylcholine in the alveolar wash, lamellar bodies, and microsomes isolated from the lung of each rabbit. Using a modification of the compartment analysis of Skinner et al. (Skinner, S. M., Clark, R. E., Baker, N., and Shipley, R. A. (1959) Am. J. Physiol. 196, 238-244), we found that surfactant phosphatidylcholine was reutilized with greater than 90% efficiency. The turnover time of the alveolar wash phosphatidylcholine was estimated to be 10.1 h and 9.3 h as measured by the 3H and 14C labels, respectively. From the ratios of alveolar wash-associated natural to synthetic phosphatidylcholine specific activities and from similar ratios obtained in 30 additional rabbits using [14C]choline-labeled natural surfactant and [3H]choline-labeled dipalmitoylphosphatidylcholine, we showed that phosphatidylcholine was reutilized intact rather than as component parts. Within 6 h of injection, the synthetic dipalmitoylphosphatidylcholine functioned metabolically as that administered in the form of natural surfactant.

Animals↗
PubMed1983

Surfactant function in respiratory distress syndrome.

Airway samples from infants with respiratory distress syndrome were recovered by suction immediately after tracheal intubation for respiratory failure. The minimum surface tension of these airway samples was 27.3 +/- 3.0 dynes/cm. Surfactant with low surface tension (1.4 +/- 1.0 dynes/cm) was recovered from these samples by centrifugation; the supernatant fractions from the samples had high minimum surface tensions. The supernatant fractions contained soluble proteins that inhibited the surface tension-lowering properties of natural sheep surfactant. Similar supernatant fractions collected from infants intubated for reasons other than respiratory distress syndrome were much less inhibitory to sheep surfactant. The minimum surface tension of sequential daily airway samples from infants with respiratory distress syndrome fell progressively to 5.7 +/- 2.4 dynes/cm on the day of extubation. These results document the presence of proteins in the airways of infants with respiratory distress syndrome that inhibit the surface tension-lowering properties of surfactant.

Animals↗