摘要:

This study was a prospective, randomized design to compare oxygenation and pulmonary hemodynamics between inhaled nitric oxide (NO) and inhaled prostacylcin (PGI2), and between inhaled and i.v. PGI2in acute respiratory failure with pulmonary hypertension. Acute respiratory failure with pulmonary hypertension was induced in 12 piglets weighing 9–12 kg by repeated lung lavages and a continuous infusion of the stable endoperoxane analogue of thromboxane. Thereafter the animals were randomly assigned either for NO or PGI2application. All animals were treated with different concentrations of NO or different doses of PGI2applied i.v. and inhaled in random order. Continuous monitoring included ECG, central venous pressure (CVP), mean pulmonary artery pressure (MPAP), mean arterial pressure (MAP), artertial oxygen saturation (SaO2), and mixed venous oxygen saturation (SvO2) measurements. NO inhalation of 10 ppm resulted in a significant increase in Pao2/fraction of inspired oxygen (FiO2) from 7.8 ± 1.34 kPa to 46.1 ± 9.7 kPa. MPAP decreased significantly from 5.1 ± 0.26 kPa to 3.7 ± 0.26 kPa during inhaled NO of 40 ppm; i.v. infusion of PGI2slightly increased oxygenation parameters. A significant increase in Pao2/FiO2up to 32.4 ± 3.1kPa was observed during PGI2aerosol delivery (p< 0.01); i.v. PGI2decreased MAP from 11.5 ± 0.39 kPa to 9.8 ± 0.66 kPa (p< 0.05) and MPAP from 5.8 ± 0.53 kPa to 4.5 ± 0.66 kPa, respectively (p< 0.05). PGI2aerosol delivery significantly decreased the MPAP to 3.7 ± 0.53 kPa (p< 0.05) without influencing the MAP. It was concluded that inhaled NO and inhaled PGI2act as selective pulmonary vasodilators in acute respiratory failure with pulmonary hypertension resulting in improved oxygenation mainly due to improved mismatch of pulmonary perfusion and ventilation. Intravenous PGI2improves oxygenation and pulmonary hemodynamics to a lesser extent than aerosolized PGI2and has the risk of systemic hypotension at a higher dose.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

To determine whether β-endorphin is involved in the laryngeal chemoreflex. we initially injected 0.01 1 mg of β-endorphin into the cisterna magna (i.c.m.) and registered the respiralory and cardiovascular patterns in 5–10-d-old piglets. From 0.1 to 1 mg of β-cndorphin i.c.m. induced a decrease in the minute volume, hearl rate, and blood pressure within 15 min. Within the next 30 min respiratory pauses accompanied by blood pressure increases and reductions in heart ratc developed, similar to the respiratory and cardiovascular pattern of the induced laryngcal chemoreflex. Based on these initial data, we decided to induce a laryngeal chemoreflex in piglets pretreated with 0.1 mg of β-endorphin i.c.m (n= 6), 0.2 mg of β-endorphin i.c.m. (n= 6), 0.1 mg of β-endorphin i.c.m. and 100 μg/kg naloxone i.v. (n= 6), 100 μg/kg naloxonc i.v. (n- 6). or water i.c.m. (n= 6). Because clevated levels of hypoxanthine in the vitreous humor may indicate hypoxia before death, we therefore measured the postmortem hypoxanthine levels in the vitreous humor. The laryngeal chemoreflex-induced apnea was shortenec in the piglet group pretreated with water i.c.m and naloxone i.v. (p< 0.01) and in the piglet group pictreated with 0.1 mg of β-endorphin i.c.m and naloxone i.v. (p< 0.05), but not significantly prolonged in the piglet groups pretreated with 0.1 or 0.2 mg of β-endorphin i.c.m. when compared with the piglcts prerreated with water i.c.m. The hypoxanthine levels in the vitreous humor were found increased after death only in piglets prctreated with 0.2 mg of β-endorphin i.c.m. before the laryngeal chemorefltex was induced (p< 0.05). We conclude that β-cndorphin is probably a mediator of apnca induced by the laryngenl chemoreflex in piglets.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Intrapulmonary distribution of a peptice-phospholipid (KJ,4) surfactant administered through an adapter permitting maintenance of positive end-expiratory pressure was compared with distribution by instillation with disconnection from mechanical ventilation in 10 surfactant-deficientMacaca mullatapreterm infants. Animals received KL4surfactant (200 mg/kg) when the arterial to alveolar (oxygen ratio) (a/Ao2) was ≤0.22 (approximately 50 min after birth) on mechanical ventilation. Six rhesus infants received bolus instillation of two half doses of KL4surfactant through an cndotrachcal tube adapter over 10–15 s while maintaining positive end-expiratory pressure (0.4 kPa) accompanied by turning to the right and left lateral positions for 60 s. In four rhesus premature infants KL4surfactant was injected as two half-dose boluses through the endotracheal tube with disconnection from mechanical ventilation while positioning the infant rhesus monkey in the right and left lateral positions for 30 s of mechanical ventilation between instillation. Acute effects on oxygen saturation were monitored, and physiologic measures of a/Ao2, mean airway pressure, and the ventilatory efficiency index were monitored over the 12-h study. Intrapulmonary distribution of KL4surfactant was determined using dye-labeled microspheres or [3H]dipalmitoyiphosphatidylcholinc-labeled KL4surfactant, measured by colorimetry or by scintillation counting. Lungs of cach monkey were processed into 50 ± 5 pieces to determine distribution of radiolabel or microspheres and for scanning electron microscopy. The drop in oxygen saturation was greater among monkey infants discoanected from the ventilator for surfactant instillation. Surfactant distribution in lung pieces inside a distribution interval 0.6–1.4 of the mean was greater among infants having instillation accompanied by positive end-expiratory pressure (p< 0.04). whereas the proportion of lung pieces receiving ≤ 10% of the normalized mean number of microspheres/mg of lung tissue was significantly greater in the group removed from the ventilator for surfactant instillation. The a/Ao2, lung compliance, and mean airway pressures improved in both treatment groups; however, the ventilatory efficiency index increased more above pretreatment values among infants treated using the endotracheal adapter with positive end-expiratory pressure (p< 0.04). More homogeneous distribution of KL4surfactant results when this surfactant is administered while maintaining positive end-expiratory pressures during surfactant instillation.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Two parameters of tidal breathing, the ratio of time to reach peak tidal expiratory flow to the total expiratory time (Tme/TE) and the ratio of volume exhaled at peak tidal expiratory flow to the total exhaled volume (dV/VT) were used to assess lung function in 21 sedated infants (aged 6–14 mo) with different degrees of airway obstruction. These parameters were compared with airway resistance as percentage predicted (Raw%) and maximum expiratory flow at functional residual capacity corrected for lung volume (VmaxFRC/TGV) VmaxFRC/TGV values correlated significantly with Tme/TE (r= 0.630,p= 0.002) as well as with dV/VT (r= 0.728.p- 0.001). Raw% values showed only a weak correlation with dV/VT (r- - 0.435,p- 0.048). We conclude that Tme/Te and dV/VT are both able to detect airway obstruction in infants and that these parameters corrclate much better with the forced expiratory flow values obtained by the rapid thoracic compression method than with airway resistance, determined by body plethysmography.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The metabolic demands of the newborn heart are met primarily by glucose and lactate. Mitochondria are impermeable to the NADH produced by these cytosolic reactions. The malate/aspanatc and a-glycerophosphate (α-GP) shuttles provide two pathways to transport reducing equivalents into mitochondria. The goals of this study were to compare the capacity of these shuttles in newborn and adult cardiac mitochondria and to measure the maximal activity of the mitochondrial enzymes involved in these shuttles. Shuttle and enzyme capacities were measured in isolated mitochondria from the left and right ventricular free wall of 0–3-d-old and adult pig hearts. Malate/aspartate shuttle capacity was nearly three times greater in the newborn left ventricle compared with adult (newborn, 616 ± 24; adult, 232 ± 28 nmol/min/mg; mean = SEM;n- 8,p< 0.0001). The capacity of the malate/aspartate shuttle of the right ventricular free wall was greater than the left in the adult heart. Despite a decrease in malate/aspartate shuttle capacity, maximal activity of mitochondrial matrix enzymes involved in this pathway were increased in adult mitochondria. α-GP shuttle activity was absent in adult myocardium. Newborn left ventricular myocardium had significant α-GP shuttle activity (44 ± 4 nmol/min/mg) due to enhanced flavin-linked mitochondrial α-GP dehydrogenase activity compated with adult. Interventricular differences in the α-GP shuttle capacity were not found in newborn or adult hearts. These findings suggest a mechanism for the substrate preference of neonatal myocardium.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Isolated, paced, isovolumetrically beating piglet hearts (n= 37) underwent retrograde aortic perfusion with a crystalloid solution during three periods: 1) baseline (coronary perfusion pressure 60 mm Hg), 2) ischemia (coronary flow 10% of baseline for ± 80 min), and 3) reperfusion (perfusion pressure returned to baseline). In one group of hearts, glycolysis (using3H20 formation from [3H]glucose) was assessed. During baseline, peak systolic pressure (PSP) was 101.1 ± 5.0 mm Hg, end diastolic pressure (EDP) 4.4 ± 0.5 mm Hg, glycolysis 970.5 ± 65.3 nmol/min/gwet‘. and myocardial glycogen 234.8 ± 12.0 μmol/gdry. During ischemia, PSP decreased to 23.3 ± 2.7 mm Hg, EDP increased to 12.3 ± 0.7 mm Hg, myocardial glycogen decreased to 181.5 ± 30.3 μmol/gdry, and lactate (≈154 μmol/gwet) and glycerol (≈930 nmol/gwen) were released. Myocardial contracture correlated with a decrease in lactate release. Glycolysis decreased to ≈400 nmol/min/gwetand remained stable, accounting for ≈50% of the lactate produced. During reperfusion, PSP recovered to 79.8 ± 3.5 mm Hg, EDP 6.6 ± 1.7 mm Hg, and glycolysis 1103.9 ± 81 nmol/min/gwet. In a second group of hearts, with similar mechanical responses, glucose oxidation (using14CO2formation from [14C]glucose) was evaluated. During baseline, glucose oxidation was 165.4 ± 15.9 nmol/min/gwet, and correlated closely (r= 0.957) with mechanical activity. With ischemia, glucose oxidation decreased to ≈17 nmol/min/gwet, yet accounted for ≈42% of the ATP produced. Upon reperfusion, glucose oxidation returned to baseline values, but now correlated poorly (r= 0.574) with mechanical activity. We conclude that for neonatal hearts undergoing severe low-flow ischemia: 1) myocardial contracture is associated with a decline in lactate release, implying impaired lactate production and/or clearance; 2) glycolysis may not fully account for the lactate released, suggesting nonglycolytic sources for energy production; 3) glycerol release is stimulated, indicating hydrolysis of triacylglycerols; 4) glucose oxidation provides an important source of ATP; and 5) glycolysis and glycose oxidation return to baseline values upon reperfusion, despite depressed contractile function, indicating dissociation between mechanical and metabolic recovery.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Ovine fetal cerebral arteries exhibit an enhanced contractile response to norepincphrine (NE) compared with newborns and adults. It is possible that β-adrenergic receptors and/or nitric oxide (NO), a putative endothelium-dependent relaxing factor, differentially modulate cerebrovascular responsiveness to NE as a function of development. The present study evaluated the effect of the β-adrenoceptor antagonist, propranolol, and the NO synthase inhibitor,NG-nitro-1.-arginine methyl ester (LNAME), on the contractile response of isolated middle cerebral artery (MCA) and basilar artery (BA) to NE during fetal development. MCAs isolated from four preterm fetal lambs (105 d of gestation), seven near-term fetal lambs (125–130 d of gestation), and eight newborn lambs (2–7 d of age) were evaluated using organ baths. BAs isolated from the near-term fetal and newborn lambs were also evaluated. Contractile reactivity of MCAs to NE decreased significantly during fetal maturation as manifested by a marked decrease inFmax(maximal relative contractile force generated) and an increase in EC50(Fmax- 100 ± 7, 41 ± 7, and 28 ± 8% of KCl contraction; EC50- 0.14 ± 0.03, 1.09 ± 0.36, and 1.07 ± 0.22 μM for preterm fetus, near-term fetus, and newborn lamb MCAs, respectively,p< 0.05). Propranolol treatment (10-5M) increasedFmax(2-fold) only for newborn lamb MCAs. Pretreatment with LNAME (104M) markedly enhanced the contractile response to NE (7-fold decrease in EC50and 2-fold increase inFmax,P< 0.05) for near-term fetus MCAs, whereas preterm fetus and newborn lamb MCAs were unaffected by the inhibitor. BAs were unresponsive to NE except for near-term fetus BAs in the presence of LNAME. The effect of NO-synthase inhibition on NE contractility was dependent on developmental age, being prominent near term. The data suggest that, in the more mature fetus, NO, presumably derived from endothelium, behaves as a functional antagonist to sympathetic vasoconstriction of the cerebrovasculature, and its apparent absence permits unrepressed sympathetic vasoconstriction in the premature brain.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Indomethacin lowers fetal and neonatal brain blood flow and may reduce the risk of periventricular-intraventricular hemorrhage. However, concerns have been raised that cerebral O2metabolism may be compromised at lower cerebral perfusion pressures. In 17 near-term lamb fetuses, changes in brain blood flow and cerebral O2metabolism (CMRo2) were measured at mean carotid arterial pressures (MCBP) ranging from 8 to 70 mm Hg. MCBP was adjusted by inflating balloon occluders around the aortic isthmus and brachiocephalic trunk. This was done before and during intrauterine pulmonary ventilation and oxygenation. Nine fetuses were pretreated with indomethacin (1 mg/kg i.v.): eight served as controls. Changes in brain blood flow were assessed from carotid arterial blood flow (Qcar, ml/min) measured with flow transducers. In 15 animals, brain blood flow was also measured intermittently by radionuclide-labeled micro-spheres (Qbrain). Qcarcorrelated closely with Qbrain(r- 0.94,p< 0.0001); this relationship was not altered by indomethacin or by ventilation with oxygen. In the nonventilated fetuses, indomethacin decreased Qcarat pressures above the lower limit of cerebral autoregulation (43 mm Hg). However, at MCBP below 44 mm Hg, Qcarwith indomethacin was not significantly different from controls. CMRo2fell when MCBP was decreased below 30 mm Hg (range 8–29 mm Hg), but there was no significant difference between control and indomethacin-pretreated fetuses. In the ventilated fetuses, indomethacin reduced the slope of the pressure-flow relationship above the lower limit of cerebral autoregulation (43 mm Hg), suggesting improved cerebral autoregulation. When MCBP was decreased below 44 mm Hg (range 10–43 mm Hg), indomethacin did not lower Qcaror CMRo2as compared with controls. We conclude that indomethacin reduced cerebral perfusion in the nonventilated fctuses and also appeared to improve cerebral autoregulatory function in the ventilated and oxygenated fetuses, without compromising cerebral metabolism at lower cerebral perfusion pressures.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Seven-day postnatal rats were subjected to unilateral common carotid artery ligation, 3 h after which they were subjected to hypoxia with 8% oxygen at 37°C for 2 h. Thereafter, they received multiple s.c. injection(s) of bicuculline (6 mg/kg) adequate to produce behaviorally apparent siezures lasting greater than 1 h (status epilepticus). Repeated episodes of status epilepticus at 2, 6, and 12 h of recovery from hypoxia-ischemia (III) produced a mortality rate of 53%. Among the survivors, there was no statistically significant difference in the extent of brain damage between convulsing and nonconvulsing HI controls, analyzed at 30 d of age. Histopathologic examination for acute lesions also indicated no difference in the severity of brain damage between dead and surviving rat pups subjected to status epilepticus, indicating that mortality was not related to the severity of prior HI brain damage. Those immature rats that died during status epilepticus exhibited lower blood glucose concentrations (1.75 ± 0.35 mmol/L) compared with surviving, convulsing animals (4.25 ± 0.51 mmol/L;p- 0.016). Glucose supplementation (0.1 mL of 50% glucose) early during status epilepticus improved survival and significantly prolonged scizure activity (90 ± 14 min) compared with nonglucose treated, convulsing littermates (47 ± 10 min;p- 0.02). Glucose supplementation did not increase the extent of brain damage despite improved survival and increased duration of seizure activity. The findings indicate that even repetitive episodes of status epilepticus in immature rats previously subjected to cerebral HI do not accentuate brain damage despite a substantial mortality. Hypoglycemia contributes to death arising from status epilepticus, and both survival and seizures can be prolonged by glucose supplementation without risk of increasing the severity of any existing brain damage.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

The manifestations of bilirubin encephalopathy include disturbances in the visual pathway (visual gaze paralysis and distorted visual perception). In the young jaundiced Gunn rat (jj) model of hyperbilirubinemia, significant differences in visual evoked potential (VEP) patterns have been recorded during development. In the present study, the effects of sulfadimethoxine (SDM) on VEP and electroretinogram (ERG) were examined in 3-wk-old jj rats. This drug displaces bilirubin from its albumin binding sites in the circulation, shifting it into tissues including the brain. Marked latency prolongations (11–20%) and reduced amplitudes (20–64%) were observed in the different wave components of the VEP. These changes were evident as early as 2 h after injection of the drug and persisted thereafter for another 4 h. On the other hand, ERG changes (significant prolongation of wave b) became apparent in these animals only 6 h after SDM injection. These results suggest that, although some changes in the retina may occur after a massive entry of bilirubin into the nervous system, the primary damage in the visual pathway after bilirubin exposure is probably beyond the retina.

ISSN:0031-3998    

出版商:OVID    

年代:1995

数据来源: OVID