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Biomedical subjects

M Ikegami

Publications and source records attributed to M Ikegami.

At least 19 recordsLinked to original sources
PubMed1992

Effects of antenatal thyrotropin-releasing hormone, antenatal corticosteroids, and postnatal ventilation on surfactant mobilization in premature rabbits.

OBJECTIVE: The effects of antenatal hormones on postnatal surfactant mobilization were evaluated in preterm rabbits. STUDY DESIGN: Pregnant rabbits were treated with vehicle, betamethasone, or thyrotropin-releasing hormone for 2 days before cesarean section at 29 days' gestation (term 31 days). Newborns were mechanically ventilated or allowed to spontaneously breathe, and groups were compared by analysis of variance. RESULTS: Neither antenatal corticosteroids nor thyrotropin-releasing hormone increased radiolabeled precursor incorporation, alveolar wash or total lung saturated phosphatidylcholine pools, lung clearance of radiolabeled rabbit surfactant, or estimated net secretion of saturated phosphatidylcholine. However, saturated phosphatidylcholine pools in alveolar wash increased 2.7-fold during the first 24 hours in spontaneously breathing rabbits versus 2.1-fold in mechanically ventilated thyrotropin-releasing hormone-treated and control rabbits (p less than 0.05). In addition, estimated net secretion of precursor-derived saturated phosphatidylcholine was 50% higher after 24 hours in spontaneously breathing rabbits. CONCLUSION: Mechanical ventilation may have hindered the mobilization of surfactant saturated phosphatidylcholine pools to the alveolar space after birth in preterm rabbits, but maternal hormonal therapies did not appear to influence this adaptive process or change surfactant metabolism.

Adrenal Cortex Hormones↗
PubMed1992

Platelet-activating factor antagonists decrease lung protein leak in preterm ventilated rabbits.

OBJECTIVE: The preterm ventilated lung is characterized by an increased protein leak from the pulmonary vascular spaces into the air spaces, which interferes with lung function and plays a role in neonatal respiratory distress syndrome. To investigate the role of platelet-activating factor in this process, platelet-activating factor antagonists were given to preterm ventilated rabbits. STUDY DESIGN: New Zealand White rabbits were delivered on day 28 of 31 days' gestation. Each rabbit pup received saline solution or one of two platelet-activating factor antagonists and were ventilated for 30 minutes with measurement of compliance, surfactant pool size, and protein leak into and out of the lung. Statistical analysis was performed with analysis of variance followed by Student-Newman-Keuls correction for multiple comparisons. RESULTS: There were no differences in lung compliance, surfactant pool size, or protein leak out of the air spaces among any of the groups. Treatment with the platelet-activating factor antagonists decreased the protein leak into the air spaces by greater than 50% and into the lung as a whole by 40% (p less than 0.01). CONCLUSION: Platelet-activating factor plays a role in the protein leak seen in the preterm lung, which contributes to neonatal respiratory distress syndrome.

Animals↗
PubMed1992

Surfactant protein A metabolism in preterm ventilated lambs.

Surfactant protein A (SP-A) metabolism was studied in vivo in 33 preterm ventilated lambs at 138 +/- 1 days gestational age by measuring recoveries of exogenously administered surfactant containing both radiolabeled SP-A and labeled saturated phosphatidylcholine (Sat PC) given via the trachea at birth. Endogenously secreted SP-A was also labeled with [35S]methionine and followed over 24 h. The exogenously labeled SP-A left the alveolar pool more rapidly than did Sat PC over the first 5 h of life (P less than 0.05), and both exogenously labeled SP-A and Sat PC were detected within lamellar bodies by 2 h, indicating uptake from the airspaces. The quantity of SP-A in alveolar washes increased about twofold from birth to 5 h of age, whereas alveolar Sat PC pools were constant over 24 h. The SP-A endogenously labeled with [35S]methionine was recovered at highest specific activities in the alveolar washes at 10 and 45 min after birth with no labeled SP-A detectable in lamellar body fractions until 2 h. The curve for endogenous SP-A labeling of lamellar bodies was similar to that for exogenous labeling, indicating that SP-A was initially secreted by a pathway independent of lamellar bodies with subsequent SP-A labeling of lamellar bodies. The kinetics of SP-A metabolism were very different than for Sat PC in preterm lambs.

Animals↗
PubMed1992

Localization of alveolar surfactant clearance in rabbit lung cells.

Localization of surfactant phospholipid clearance in lung cells was investigated in vivo in rabbits using radiolabeled dipalmitoylphosphatidylcholine (DPPC) and 1,2-dihexa-decyl-sn-glycero-3-phosphocholine (DPPC-ether), a phospholipase A1- and A2-resistant analogue of DPPC. After intratracheal injection of liposomes of the labeled lipids associated with unlabeled surfactant, adult rabbits were killed in groups of three to five at 0, 4, 12, and 24 h with recovery of bronchoalveolar lavages for alveolar macrophages and surfactant. Type II cells and tissue-associated macrophages were isolated on Percoll gradients following elastase and trypsin digestion of the lungs. Radiolabel recoveries as saturated phosphatidylcholine were measured in alveolar wash, alveolar macrophages, lung tissue, and the type II cell and mixed cell bands from the Percoll gradients. Cost accounting of label demonstrated similar recoveries at 0 h, but significantly more DPPC-ether compared with DPPC in cells at later times, indicating ineffective degradation of the DPPC-ether. Internalization of the lung tissue-associated labels into cells was time dependent. At all times, greater than 65% of the cell-associated labels were recovered in type II cells, indicating the primary role for these cells in clearing alveolar surfactant phospholipid in vivo. The total contribution of alveolar macrophages to the overall clearance was approximately 20%.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1992

Different ventilation strategies alter surfactant responses in preterm rabbits.

The effect of ventilation strategy on in vivo function of different surfactants was evaluated in preterm rabbits delivered at 27 days gestational age and ventilated with either 0 cmH2O positive end-expiratory pressure (PEEP) at tidal volumes of 10-11 ml/kg or 3 cmH2O PEEP at tidal volumes of 7-8 ml/kg after treatment with one of four different surfactants: sheep surfactant, the lipids of sheep surfactant stripped of protein (LH-20 lipid), Exosurf, and Survanta. The use of 3 cmH2O PEEP decreased pneumothoraces in all groups except for the sheep surfactant group where pneumothoraces increased (P < 0.01). Ventilatory pressures (peak pressures - PEEP) decreased more with the 3 cmH2O PEEP, low-tidal-volume ventilation strategy for Exosurf-, Survanta-, and sheep surfactant-treated rabbits (P < 0.05), whereas ventilation efficiency indexes (VEI) improved only for Survanta- and sheep surfactant-treated rabbits with 3 cmH2O PEEP (P < 0.01). Pressure-volume curves for sheep surfactant-treated rabbits were better than for all other treated groups (P < 0.01), although Exosurf and Survanta increased lung volumes above those in control rabbits (P < 0.05). The recovery of intravascular radiolabeled albumin in the lungs and alveolar washes was used as an indicator of pulmonary edema. Only Survanta and sheep surfactant decreased protein leaks in the absence of PEEP, whereas all treatments decreased labeled albumin recoveries when 3 cmH2O PEEP was used (P < 0.05). These experiments demonstrate that ventilation style will alter a number of measurements of surfactant function, and the effects differ for different surfactants.

Air Pressure↗
PubMed1992

Antenatal ambroxol effects on surfactant pool size and postnatal lung function in preterm ventilated rabbits.

Following maternal treatments with 50 mg/kg/day ambroxol for 2 or 3 days before delivery at 28 days gestation, preterm rabbits were ventilated to evaluate lung function. Subsequently, surfactant saturated phosphatidylcholine (SatPC) pool sizes were measured. One half of the ambroxol treated and control rabbits were given surfactant at delivery. Although surfactant improved lung function comparably for control and ambroxol treated rabbits, ambroxol treatments did not change ventilatory pressure requirements, compliances, or the recovery of intravascular labeled albumin in the lungs. Ambroxol treatments tended to increase lung volumes as evaluated by pressure-volume curves. The ambroxol treatments significantly increased lung tissue SatPC by 22%, but there were no changes in alveolar SatPC pool values. These results do not indicate a large effect of ambroxol on lung function in preterm rabbits.

Ambroxol↗
PubMed1992

Metabolism of exogenously administered surfactant in the acutely injured lungs of adult rabbits.

Acute lung injury was induced in adult rabbits with a subcutaneous injection of N-nitro-so-N-methylurethane (NNNMU). Clearance of saturated phosphatidylcholine (Sat.PC) from a treatment dose of exogenous surfactant (100 mg/kg) in the injured lungs of these rabbits was similar to normal, control rabbits when measured 24 h after treatment. However, total Sat.PC pool sizes in both the alveolar wash and total lung at this time point were significantly lower for the injured lungs than for the control lungs (p less than 0.05), implying altered endogenous surfactant metabolism in response to surfactant treatment in the injured animals. Although both injured and control animals had comparable ratios of small to large surfactant aggregates, as measured by differential centrifugation of alveolar wash 5 min after treatment, by 24 h this ratio had increased 5-fold in the control animals and remained unchanged in the injured animals. This indicated diminished conversion of large surfactant aggregates to the smaller forms in lung injury. In vivo functional studies of these aggregates were performed by intratracheal injection into surfactant-deficient preterm rabbits. Large aggregates from normal adult rabbits given surfactant had superior functional properties than did the surfactant used for treatment alone, which in turn was better than large aggregates isolated from NNNMU-injured rabbits treated with surfactant. This indicates that the alveolar environment influenced the function of the exogenously administered surfactant differently in normal and injured rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1992

Lung albumin recovery in surfactant-treated preterm ventilated lambs.

Preterm ventilated animals and infants with respiratory distress syndrome (RDS) develop proteinaceous alveolar edema. To study the effect of postnatal age on intravascular radiolabeled albumin accumulation into lungs, preterm lambs at 132 days gestational age were ventilated after treatment with sheep surfactant or cow surfactant extract for periods as long as 24 h. Lambs not treated with surfactant were studied for only 5 h because of severe respiratory failure. All lambs were given radiolabeled albumin by intravascular injection 1 h before they were killed, and the net recovery of the labeled albumin was measured in the lung tissue and air space as quantified by alveolar lavage. Net 1-h radiolabeled albumin recoveries in the lungs decreased from 5 to 6% soon after birth to 0.9% at 24 h in the surfactant-treated groups (p less than 0.01). At 3 h there was less labeled albumin recovery by alveolar lavages in lambs treated with sheep surfactant than in control lambs and lambs treated with cow surfactant extract (p less than 0.05). Protein in alveolar washes from lambs treated with cow surfactant extract exceeded that in lambs treated with sheep surfactant at 3 h (p less than 0.05), but protein recoveries had decreased to similar values by 24 h, indicating a net clearance of air-space protein. These studies demonstrate a sixfold decrease in net albumin accumulation from birth to 24 h of age despite continued ventilation and oxygen exposure of the premature lamb lungs.

Animals↗
PubMed1992

In vitro conversion of surfactant subtypes is altered in alveolar surfactant isolated from injured lungs.

Pulmonary alveolar surfactant can be separated into different subtypes on the basis of their buoyant densities. These subtypes have been characterized as ultraheavy and heavy forms, which are surface-active, and light forms, which are less surface active. The ratio of these subtypes was altered in an animal model of acute lung injury that contributed to the physiologic abnormalities. We used an in vitro method of surface-area cycling to compare conversion of heavy subtypes isolated from injured and from normal lungs. Lung injury was induced in adult rabbits with a subcutaneous injection of N-nitroso-N-methylurethane (NNMU). Conversion of NNMU-injured heavy subtypes to light subtypes was significantly greater than normal heavy subtype conversion at each time point studied from 60 to 180 min of cycling (p less than 0.01). Surfactant protein A (SP-A) was added to heavy subtypes, with no effect on conversion when 1.5% SP-A was added, but the addition of 4.5, 10.5, and 22.5% caused complete conversion to ultraheavy forms with no cycling. With subsequent cycling, there was greater conversion from ultraheavy to lighter subtypes for normal surfactant material than for NNMU-injured material (p less than 0.05). We conclude that the altered ratio of surfactant subtypes in the alveolar lavage of injured lungs was due to a greater conversion of these subtypes within the alveolar space. Furthermore, SP-A may play an important role in the metabolism of alveolar surfactant both in normal and in injured lungs.

Animals↗
PubMed1992

[Evaluation of kidney graft function with dynamic MRI--preliminary report].

The value of dynamic magnetic resonance imaging (MRI) in the examination of the function of transplanted kidneys was examined. Dynamic MRI was performed on 14 renal transplant patients. After the injection of Gd-DTPA (dimeglumine gadopentetate), we used small tip angle gradient echo (STAGE) technique with a flip angle of 20 degrees. The cortex was higher in signal intensity of well functioning grafts than the medulla before the injection in Gd-DTPA. Signal intensity of the cortex decreased after 30 seconds. After 1 minute the signal intensity of the cortex recovered and low intensity band meaning passage of Gd-DTPA at corticomedullary differentiation was displayed. Signal intensity of the medulla decreased after 3 minutes. Signal intensity of the parenchyma of transplanted kidney after 5 minutes was much the same as that before injection. Image of poor functioning grafts displayed unclear figures. Time-intensity values of both cortex and medulla in well functioning grafts decreased rapidly after about 2 minutes, and rose thereafter. Time-intensity curves of both cortex and medulla were almost flat on and after 5 minutes. Time-intensity curves of both cortex and medulla in poor functioning grafts were almost flat through out the examination. We concluded that effective parameters of the graft function for the time-intensity curve were delta I1 and delta I2. Dynamic MRI was suggested to be useful in the evaluation of kidney graft function.

Contrast Media↗
PubMed1992

Reduction of portal pressure by chronic administration of isosorbide dinitrate in patients with cirrhosis: effects on systemic and splanchnic hemodynamics and liver function.

We investigated the chronic effects of isosorbide dinitrate on systemic and splanchnic hemodynamics and liver function in 13 patients with liver cirrhosis and portal hypertension. Placebo administration for 4 wk (n = 4) had no significant effects on these parameters. In contrast, oral administration of 40 mg/day of isosorbide dinitrate for 4 wk (n = 9) caused a significant fall in portal pressure (-18%, p less than 0.02), as evaluated by measurements of the hepatic venous pressure gradient with no modification in hepatic blood flow (from 0.72 +/- 0.29 to 0.71 +/- 0.34 L/min, NS), suggesting decreased intrahepatic or collateral vascular resistance. On the other hand, there was no significant correlation between the changes in mean arterial pressure and hepatic venous pressure gradient (r = 0.42). Thus, it seems unlikely that a reduction in portal blood inflow by baroreceptor-mediated reflex splanchnic vasoconstriction contributed to the fall in portal pressure. In addition, this drug had no adverse effects on liver function, as evaluated by measurements of the intrinsic clearance. These results suggest that chronic administration of isosorbide dinitrate could be a potentially useful and associated with cirrhosis.

Adult↗
PubMed1992

Nicardipine infusion improved hepatic function but failed to reduce hepatic venous pressure gradient in patients with cirrhosis.

We investigated the effects of nicardipine on systemic and splanchnic hemodynamics and on liver function in 16 patients with cirrhosis and portal hypertension. Patients received a continuous infusion of 0.3 mg/min of nicardipine (n = 10) and a control infusion (n = 6). No significant changes were observed after a control infusion. In contrast, systemic vasodilatation, evidenced by a significant fall in mean arterial pressure (-14%, p less than 0.01) and systemic vascular resistance (-30%, p less than 0.01), increased heart rate (+8%, p less than 0.01) and cardiac output (+21%, p less than 0.01), and increased hepatic blood flow (+43%, p less than 0.01) were observed at 60 min after a continuous infusion of nicardipine. Although nicardipine improved hepatic function (intrinsic clearance from 0.29 +/- 0.13 to 0.33 +/- 0.15 L/min, p less than 0.05), portal pressure evaluated by hepatic venous pressure gradient was not reduced significantly (from 16.3 +/- 4.9 to 15.1 +/- 5.7 mm Hg; NS). We conclude that a continuous infusion of nicardipine improves liver function but has no beneficial effect on portal pressure in patients with cirrhosis.

Adult↗
PubMed1992

Portohepatic pressures, hepatic function, and blood gases in the combination of nitroglycerin and vasopressin: search for additive effects in cirrhotic portal hypertension.

We studied the effects of the combination of nitroglycerin and vasopressin on portohepatic hemodynamics, hepatic function, and blood gases in nine patients with cirrhosis and portal hypertension. Vasopressin infusion at a dose of 0.4 U/min caused a significant fall in portal pressure, which is evaluated by portal venous pressure gradient (-34%, p less than 0.01), associated with a decrease in hepatic perfusion (-33%, p less than 0.01) and intrinsic clearance (-20%, p less than 0.01) after 30 min. The arterial oxygenation, however, was not modified (paO2; from 73 +/- 8 to 72 +/- 7 mm Hg, NS). Nitroglycerin infusion at a dose of 100 micrograms/min was then administered for 20 min. The addition of nitroglycerin produced a further reduction in free portal venous pressure (-12%, p less than 0.01), but this was not associated with a significant improvement in both hepatic perfusion (+16%, NS) and intrinsic clearance (-7%, NS). In addition, there was a significant fall in arterial oxygenation (paO2; from 72 +/- 7 to 59 +/- 5 mm Hg, p less than 0.01). We conclude that the addition of nitroglycerin to vasopressin has a beneficial effect on free portal venous pressure, but does not have hepatic benefit. Moreover, sufficient care must be taken, when treating portal hypertension with this combination, to avoid arterial hypoxemia.

Aged↗