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PubMedDate not supplied

Amniotic sac infection syndrome features fetal lung neuroendocrine cell hyperfunction.

Neuroendocrine cells (NEC) are abundant in fetal and neonatal lungs, but reduced in infants with hyaline membrane disease. Perinatal neuroendocrine cell hyperplasia (NCH) has been reported in the hypoplastic lung in diaphragmatic hernia, bronchopulmonary dysplasia, and Wilson-Mikity syndrome. Since we are unaware of any reports on NCH in fetal inflammatory conditions, this report addresses the NEC in fetuses with congenital pneumonia. Twenty-one fetuses/neonates with congenital pneumonia, autopsied between 1995 and 2001, were compared to 21 fetuses without a congenital infection matched for gestational age. Lung sections were immunostained for chromogranin, bombesin, calcitonin, and synaptophysin. Proportions of immunopositive cells lining 20 consecutive bronchioles calculated from digital images were significantly higher in the study than the control group for chromogranin (1.8 vs. 0.8%, P = 2.4 E-06), calcitonin (1.2 vs. 0.7%, P = 0.005), and bombesin (1.1 vs. 0.7%, P = 0.005). There was no difference in synaptophysin (11.7% vs. 12.6%, P = 0.07). The absence of significant differences in the synaptophysin ratio excludes simple NCH in the study group. The synchronous increase in three neurohormones is indicative of NEC hyperfunction, due to either altered enzymatic inactivation by neutral endopeptidase, known to be reduced in adult lung inflammation, or by an increase in expression of the neurohormone genes. These data indicate that NEC hyperfunction may be responsible for the deranged fetal/neonatal lung function and circulatory adaptation, and contribute to the lethality of the amniotic sac infection syndrome.

Bombesin↗

PubMed1998

Modified Toupet wrap for gastroesophageal reflux in childhood.

UNLABELLED: It was the aim of our study to follow up our clientele of infants and children who had undergone a partial (posterior) Toupet wrap or modified Toupet wrap. METHODS: All 22 children who had undergone a posterior partial wrap within a 4-year period were followed up for 4.0 years (0.6-5.7 years). 36.4% of children had associated anomalies such as operated esophageal atresia, operated congenital diaphragmatic hernia, Gregg's syndrome or arthrogryposis multiplex congenita. 14% of children suffered from some form of neurological impairment. Prior to operation the 4 main examinations for detection and documentation of gastroesophageal reflux (GER) disease were carried out where possible. Five children underwent Toupet fundoplication and in 17 children a modified Toupet fundoplication with reinforcement of the wrap fixation using a Vicryl-mesh was applied. A pH-metric study and upper gastrointestinal series with reflux testing were done in all 22 children at least 6 months postoperatively. Successful control of GER was documented in 21 of 22 children (95.5%). In the remaining child a reoperation was necessary to correct recurrence of a sliding hiatal hernia and GER. In three children (13.6%) postoperative complications occurred within the first 2 weeks following fundoplication and were managed medically. Following the postoperative 24-hour pH-metric study and the upper gastrointestinal series with reflux testing, one child with normal results at these investigations was lost to follow-up. The remaining 21 children were followed up for another 10 months to 5 years. Four children (18.2%) were found to suffer from functional complications (mild dumping syndrome, retrosternal pain, vomiting during episodes of asthma, dysphagia). No gas bloat syndrome occurred within the follow-up interval and all children were able to belch and vomit. There was no mortality in our limited series. Our series indicates that the partial (posterior) Toupet wrap and the modified Toupet fundoplication are safe and effective procedures for surgical correction of GER in children which preserve the ability of infants and children to belch and vomit.

Adolescent↗

PubMed1978

Value of the QRS complex in assessing left ventricular ejection fraction.

The relation between electrocardiographic findings and the angiographic left ventricular ejection fraction and the augmented ejection fraction after a premature ventricular contraction was investigated in 73 patients with documented chronic coronary artery disease. The patients were separated into four groups according to the presence or absence of abnormal Q waves. Twenty-four patients had diaphragmatic myocardial infarction, 21 had anterior myocardial infarction, 15 had both and 13 had no myocardial infarction. There was no statistically significant differences in cardiac index, left ventricular end-diastolic pressure or number of coronary vessels showing critical narrowing in the four groups. The sum of R waves (in mv) in leads aVL, aVF and V1 to V6 (sigmaR) was correlated with the ejection fraction (EF) and the augmented ejection fraction (EFa). EF in percent = 6.6 sigmaR mv + 9.4 (no. =73, r = 0.61); and EFa in percent = 8.6 sigmaR mv + 11.0 (no. = 73, r = 0.77). Among patients with sigmaR of less than 4.0 mv, augmented ejection fraction was less than 0.45 in 73 percent; among patients with sigmaR of 4.0 mv or more the augmented ejection fraction was greater than 0.45 in 93 percent (P less than 0.001). Thus, the sigmaR, calculated from six precordial and two augmented leads in patients with chronic coronary artery disease, correlated with both ejection fraction and augmented ejection fraction. The electrocardiogram in patients with coronary artery disease may prove useful as a simple, readily available and noninvasive guide in the assessment of left ventricular function in patients with coronary artery disease.

Blood Pressure↗

PubMed1995

Submental and diaphragmatic muscle activity during and at resolution of mixed and obstructive apneas and cardiorespiratory arousal in preterm infants.

Pathomechanisms involved in obstructive apneas remain obscure. Apnea arousal failure has been proposed as a cause for sudden death during sleep. The present study hypothesizes an interdependency between upper airway dilating submental muscle electromyogram (EMG) activity (EMGsub), diaphragmatic muscle activity (EMGdia), incidence of bradycardia, and transcutaneous measured PO2 (tcpO2) upon termination of apnea. Polygraphic recordings, including surface EMG (EMGsub, EMGdia), EEG, ECG, and transcutaneous PO2/PCO2 (tcpO2/tcpCO2) were performed on 10 preterm infants at 36, 40, 44, and 52 wk of conceptional age. EMGsub increased initially, then decreased in 28 of 33 non-rapid eye movement (N-REM) sleep apneas (REM: 35 of 69 events). This correlated with a decrease of tcpO2 during N-REM sleep (p < 0.05). A parallel decrease of EMGsub and EMGdia was correlated with the occurrence of bradycardia (REM and N-REM: p < 0.01). Concomitant termination of apnea and bradycardia (n = 22), occurred in the presence of a phasic, simultaneous activation of EMGsub and EMGdia in 64% of REM sleep and in 79% of N-REM sleep-related event, was characterized by a deep inspiration preceded by a short expiration, and correlated with the extent of tcpO2-decline during REM sleep apneas (p < 0.05). In one apnea with bradycardia that progressed to asystolia, this mechanism was missing, but was evoked by a slight tactile stimulation, where-upon cardiorespiratory functions were immediately reestablished whereas N-REM sleep continued uninterrupted. Our data demonstrate an interdependency between changes of EMGsub and EMGdia activity, tcpO2 decline, and occurrence of bradycardia. A "cardiorespiratory arousal" terminated apneas and bradycardia without a change in sleep phase.

Bradycardia↗

PubMed1992

[Dyspnea and inspiratory muscle function during exercise in severe chronic obstructive pulmonary disease (COPD)].

Role of inspiratory muscle function in the genesis of dyspnea in COPD patients has yet to be fully studied. The present study investigated the possible relationship between respiratory muscle function and the sensation of dyspnea (modified Borg Scale) during exercise in eight patients with severe COPD (FEV1 0.61L +/- 0.15L). The electrical activity of the diaphragm (EMGdi) was recorded with esophageal electrodes, and that of sternomastoid muscle (EMGsm) was recorded from the surface electrodes. The ratio of high frequency (150 to 350 Hz) to low frequency (20 to 47 Hz) power (H/L) of EMGdi and EMGsm was analyzed to assess inspiratory muscle fatigue, which was determined by a 20% fall of H/L ratio from the control value. Flow, volume, esophageal (Pes) and transdiaphragmatic pressure (Pdi) were measured. Tension time index (TTdi) was calculated from Pdi and the ratio of inspiratory time to total time for one cycle (T1/TTOT). At rest, we measured maximal esophageal pressure (Pesmax), maximal transdiaphragmatic pressure (Pdimax), maximal EMGdi (EMGdimax) and EMGsm (EMGsmmax). Progressive treadmill exercise test was performed, stating with 3 minutes' walk at a speed of 0.75 mph at 0% grade, subsequently increasing the velocity at a rate of 0.25 mph and the elevation at a rate of 4% per stage. Exercise was discontinued at maximum respiratory effort sensation. Six of the eight patients showed diaphragmatic fatigue at their maximal exercise. With diaphragmatic fatigue, these patients were extremely dyspneic (Borg scale 9 or 10), and terminated the exercise. There were high correlations between the Borg scale and VE/MVV, and Pes/Pesmax and EMGsm/EMGsmmax, however, TTdi and EMGdi/EMGdimax showed less correlation with the Borg scale.(ABSTRACT TRUNCATED AT 250 WORDS)

Dyspnea↗

PubMed1978

Regulation of the activity of respiratory muscles during sleep.

This review concerns studies on the electrograms of respiratory muscles carried out in unrestrained sleeping cats. The respiratory unit discharges of the diaphragm and intercostal muscles undergo only quantitative changes from quiet wakefulness to synchronized sleep. Intercostal postural activity is also evident whereas such activity is practically absent in diaphragmatic electrograms. During desynchronized sleep the activity, both postural and respiratory, of intercostal muscles is tonically depressed and highly irregular, while diaphragmatic electrograms are scarcely affected, except for random disturbances related to the phasic events of this stage of sleep (rems, muscle twitches). The changes in the activity of intercostal muscles do not depend on modifications of the activity of respiratory centres as phrenic motor neurones are not tonically depressed. Only strong phasic influences of non-respiratory brain stem structures may affect phrenic motor neurones during desynchronized sleep. The depression of intercostal respiratory activity during this stage of sleep rather depends on the tonic inhibitory influences of brain stem structures on spinal motor neurones affecting also intercostal postural activity. The respiratory frequency during desynchronized sleep increases and decreases above eupneic and below polypneic values of synchronized sleep, respectively. Such a phenomenon cannot be related to the tonic brain stem inhibition of spinal motor neurones occurring during desynchronized sleep as it is unlikely that the same influence may elicit two opposite effects. These effects can be better explained on the basis of a release of respiratory centres from higher controls, particularly hypothalamic. In conclusion, the clear dichotomy in respiratory motor innervation between synchronized and desynchronized sleep reveals a basic change in respiratory regulation whose functional significance is still obscure.

Animals↗

PubMed2000

Unsuspected pseudophysiologic emphysema in chronic persistent asthma.

The current literature emphasizes the role of airway remodeling in chronic persistent asthma and its putative effect on causing fixed expiratory airflow limitation. We studied 18 adults with chronic persistent asthma; 12 men, six women, age 59 +/- 15 yr (mean +/- SD) with fixed expiratory airflow obstruction. We measured lung elastic recoil and examined the mechanism of expiratory airflow limitation. Diaphragmatic strength was also measured in six asthmatics, using both sniff and partially occluded airway technique. All 18 asthmatics had markedly abnormal maximal expiratory flow-volume curves at both high and low lung volumes. Hyperinflation was present at residual volume (RV), FRC, and TLC in all subjects. Diffusing capacity was normal or elevated and lung computed tomography (CT) was normal in all 18 asthmatic subjects. There was a significant loss of lung elastic recoil in three of four asthmatics age 30 to 49, all five age 51 to 60 yr, and seven of nine age 61 to 82 yr. Maximal expiratory airflow limitation in only four elderly asthmatics and only at low lung volumes was due completely to loss of lung elastic recoil. In the others, we estimate the reduction in lung elastic recoil was responsible for 35% reduction in maximal expiratory airflow at 80% of TLC, and 55% at 70% of TLC. Despite hyperinflation, transdiaphragmatic pressures and strength were normal. The mechanisms responsible for loss of lung elastic recoil remain elusive. The high incidence of loss of lung elastic recoil in chronic persistent asthma was unexpected, and its contribution to abnormal lung function needs to be emphasized.

Adult↗

PubMed2000

Analysis of the anatomic changes in the thoracic cage after a lung resection using magnetic resonance imaging.

The thoracic cage after a lung resection is filled by the remaining lobes, the elevated diaphragm, the diminished thoracic cage, and by mediastinal shifting. The changes in the thorax after a lung resection were quantified using magnetic resonance imaging. The study group consisted of 39 patients who had undergone a lobectomy, four who had undergone a pneumonectomy, and 14 controls. The left ventricular angle, ascending aortic angle, mediastinal shift, longitudinal length of the thoracic cage, the distance between the thoracic apex and the level of the aortic valve, and diaphragmatic elevation were all measured. After a right lower lobectomy, the mediastinum shifted more rightward than after a right upper lobectomy. The diaphragm became more greatly elevated after a right upper lobectomy than after a right lower lobectomy. When a chest wall resection was added to a right upper lobectomy, the mediastinal anatomical changes decreased. After a left upper lobectomy, the degree of mediastinal shifting was greater than after a left lower lobectomy. A left upper lobectomy shifted the mediastinum at the level of the right atrium. This method is easily reproducible and was found to be effective for quantifying the changes in the thorax after a lung resection.

Case-Control Studies↗

PubMed1993

Transient severe respiratory distress mimicking pulmonary hypoplasia in preterm infants.

Three preterm infants are described who had respiratory failure immediately after birth. For each, historical factors (extrauterine abdominal pregnancy; ruptured membranes with oligohydramnios for 14 weeks; congenital diaphragmatic hernia) and the initial postnatal course were suggestive of pulmonary hypoplasia. However, with vigorous resuscitation each infant showed rapid improvement in pulmonary status for several hours. Two infants survived with no apparent pulmonary sequelae; the third had almost complete resolution of pulmonary disease but died from gastrointestinal complications. Thus some infants with historical and clinical indicators of severe pulmonary hypoplasia do not have hypoplastic lungs and respond favorably to resuscitation. The causes of the respiratory distress and of its rapid resolution are not known. On the basis of this experience, even infants with historical factors suggesting pulmonary hypoplasia and with postnatal respiratory distress should receive vigorous resuscitation.

Diagnosis, Differential↗

PubMed1988

Regional variation in pericardial contact pressure in the canine ventricle.

We studied eight open-chest dogs to determine whether there is regional variation in pericardial contact pressure (PCP). Flat, air-filled balloons were used to measure PCP simultaneously over the lateral walls of the right and left ventricles while cardiac volume was varied by dextran infusion. End-diastolic and mean PCP were significantly higher over the left than right ventricle at high (20.3 +/- 1.0 mmHg) and middle levels (13.7 +/- 0.9 mmHg) of left atrial pressure. At high left atrial pressures, the end-diastolic PCP over the lateral left ventricle was 9.1 +/- 2.4 mmHg compared with 4.3 +/- 2.3 mmHg over the lateral right ventricle (P less than 0.05). At middle levels of left atrial pressures, end-diastolic PCP was 6.2 +/- 3.5 mmHg over the left ventricle and 1.5 +/- 2.4 mmHg over the right ventricle (P less than 0.05). These variations in PCP persisted after severing the pericardial diaphragmatic attachments and after turning the dogs such that one or the other balloon was dependent. Regional distribution of PCP was studied by positioning a single balloon sequentially at multiple ventricular sites. PCP was consistently higher over the lateral wall of the left ventricle than either the anterior or posterior walls of the right or left ventricle. After aortic occlusion, end-diastolic PCP increased more over the left than right ventricle. In contrast, with pulmonary artery occlusion, end-diastolic PCP increased more over the right than left ventricle. Pericardial pressure varies regionally, and a single pericardial pressure may be an oversimplification when used to describe pericardial restraint on the cardiac volume.

Animals↗

PubMed1977

Gastro-oesophageal reflux, hiatus hernia and the radiologist, with special reference to children.

Gastro-oesophageal reflux can lead to peptic oesophagitis and stricture formation. This is particularly true in infants in whom the condition should be suspected if the patient presents with vomiting, anaemia and failure to thrive. The anatomy of the oesophago-gastric junction is described. The inferior oesophageal sphincter is the main barrier to reflux, and marks the functional junction between oesophagus and stomach. It is under nervous and hormonal control. It is weak in the neonate who therefore frequently refluxes. An hiatus hernia can cause problems due to its bulk but the main problem of peptic oesophagitis is due to gastro-oesophageal reflux. The radiological examination should be carried out carefully with the patient swallowing in a prone position. The patient should be put in the Trendenlenberg position and compression applied to the abdomen. Reflux is intermittent and a negative examination should be repeated if the clinical findings suggest a diagnosis of peptic oesophagitis. Associated pyloric stenosis should always be excluded. Radiological examination of the gastro-oesophageal junction remains the quickest, simplest, and most convenient and safe technique as long as its limitations are appreciated.

Child↗

PubMed2007

Hospital stays, hospital charges, and in-hospital deaths among infants with selected birth defects--United States, 2003.

Birth defects (BDs) are conditions that 1) result from a malformation, deformation, or disruption in one or more parts of the body; 2) are present at birth; and 3) have a serious, adverse effect on health, development, or functional ability. BDs are leading causes of pediatric hospitalizations, medical expenditures, and infant mortality. To estimate national hospital charges and rates of in-hospital deaths for a greater number of specific BDs than estimated in previous reports, investigators at the University of Arkansas for Medical Sciences and CDC used the Healthcare Cost and Utilization Project 2003 Kids' Inpatient Database (KID), developed and distributed by the Agency for Healthcare Research and Quality. KID is a 10% sample of hospital discharges after uncomplicated births and an 80% sample of all other pediatric discharges from 36 participating states. Data are weighted to represent all pediatric hospitalizations in the United States. The investigators analyzed hospital stays during 2003 for newborn infants with any of 35 BDs. This report describes the results of that analysis, which indicated substantial variation among BDs regarding average length of stay, average hospital charge, and the incidence of in-hospital deaths. Average length of stay was greatest for infants with surgically repaired gastroschisis or omphalocele. Average hospital charges were highest for infants with hypoplastic left heart syndrome and common truncus arteriosus. Although anencephaly, trisomy 13, and trisomy 18 were associated with the highest rates of in-hospital death, the largest total numbers of deaths associated with neonatal hospitalizations occurred in infants with diaphragmatic hernia and renal agenesis. Further studies are needed to distinguish outcomes for infants with isolated and multiple defects and to assess longer-term outcomes.

Congenital Abnormalities↗

PubMedDate not supplied

[Esophageal manometry in patients with sliding hiatal hernia].

This presents the method to be followed for the valuation of the gastro-esophagic function in patients with sliding hiatal hernia, twenty-one patients with this diagnosis were studied through X-Rays. Besides gastric and esophagic endoscopy, a complete clinical examinations was made to compare the information obtained from the studies, with the direct measurement of the contractions of the esophagus and the lower sphincter through conventional manometric methods. The relationship between the simptoms and the clinical procedures done in the patients were observed as was the usefulness of esophagic manometry to detect not only the direct pressure of the gastro-esophagic sphincter, but also to determine the concurrent motor changes that can occur in patients which show hiatal hernia. The benefit of this studies to decide the therapeutic handling, specially surgical, is discussed.

Esophagogastric Junction↗

PubMedDate not supplied

Matrix metalloproteinases-2 and -9 and their endogenous tissue inhibitors in tissue remodeling after sealing of the fetal membranes in a sheep model of fetoscopic surgery.

OBJECTIVES: We studied collagen plugging of the fetoscopic access site in an in vivo fetal lamb model for fetoscopic surgery and possible role for matrix metalloproteinase (MMP)-2 and -9 and tissue inhibitors (TIMPs). METHODS: Eight ewes had fetoscopic balloon occlusion of the trachea as an experimental treatment for congenital diaphragmatic hernia between days 88 and 99 of gestation (term 145 days) with sampling of amniotic, allantoic, and tracheal fluid. Nonoperated cotwins were used as controls. The fetoscopy port was closed using a collagen plug. Ten days (range 9-12) later, fluids were sampled and plug sites collected for histologic analysis. Activity of MMP-2 (72 kDa, gelatinase A) and MMP-9 (92 kDa, gelatinase B) was determined in the fluids by zymography and secretion of TIMPs (27-30 kDa; TIMP-1, glycosylated TIMP-3 and TIMP-4, 24 kDa; unglycosylated TIMP-3, 21 kDa; TIMP-2) by reverse zymography and quantified by densitometric analysis. RESULTS: No pregnancy was complicated by amniorhexis or preterm labor. At cesarean, normal volumes of amniotic and allantoic fluid were present in all cases. Histology of the plug sites revealed good integration of the collagen plug without complete restoration of membrane integrity. MMP-2, MMP-9, and TIMPs were detected in all fluids. In the operated animals, significantly (P <.05) higher activity of MMP-9 was found in amniotic fluid, with lower concentrations of TIMPs in allantoic fluid (P <.01). Tracheal occlusion was associated with a significant (P <.02) increase in both MMP-2 and -9 in tracheal fluid. CONCLUSION: Collagen plugging of the fetoscopic access port sites in sheep resulted in functionally effective sealing of the fetal membranes. Changes in MMP-2, MMP-9, and TIMPs suggest an active remodeling of both the fetal lung and the fetal membranes.

Amnion↗

PubMed2003

Neck and abdominal muscle activity during a sniff.

Measurement of sniff nasal inspiratory pressure (SNIP) is now used widely as a simple, non-invasive assessment of global respiratory muscle strength, even though the technique evolved originally from measurements of trans-diaphragmatic pressure (Pdi) that reflect the status of the diaphragm. The relative participation of major respiratory muscles, apart from the diaphragm, in the generation of SNIP is not known. Therefore, we examined the activity during a sniff of both neck and abdominal "accessory" muscles. In seven young adults we implanted fine wire EMG electrodes under direct vision with high-resolution ultrasound into scalene, sternocleidomastoid, trapezius, and transversus abdominis. SNIP was measured during sniffs that were short and sharp, from low to maximal intensity, in both standing and supine postures. Mean maximum SNIP was -105.6cmH2O (SD 32.9) in supine and -94.5cmH2O (26.6) in the standing posture, (difference NS). In every subject, scalene activity appeared even at the lowest SNIP, and increased linearly with increasing SNIP. Sternomastoid activity appeared at higher SNIP levels in three of seven subjects. By contrast, trapezius activity was never present at low SNIP, and appeared in only 2 subjects at maximum SNIP. Sniff abdominal expiratory activity was inconsistent with no activity of transversus in four of seven subjects even at greatest SNIP. Thus, we observed differential activation among these non-diaphragm respiratory muscles during SNIP; while some accessory muscles were very active, others were unlikely to contribute to generation of SNIP. Clinically, this indicates SNIP will be impacted unequally by loss of function of specific respiratory muscles.

Abdominal Muscles↗

PubMed1973

Contribution of various inspiratory muscles to ventilation and the immediate and distant effect of diaphragmatic paralysis.

The contribution of the diaphragm and that of the other inspiratory muscles (scaleni and all the other extradiaphragmatic muscles) at different levels of tidal volume (VT) and during static inspiratory efforts of various strengths has been studied in supine anaesthetized rabbits by blocking phrenic conduction with an electrotonic current. Rabbits spinalized at T1 were used to measure the separate contribution of the scaleni. When the vagi are left intact there is an hyperactivity of the extradiaphragmatic muscles during the phrenic block which has been ascribed to Hering-Breuer reflexes. The relative contribution of the diaphragm to tidal volume, during quiet breathing, appears to approach 9O percent and is reduced to 75 percent during the maximum tidal volume attained. The scaleni appear to account for about 1/3 of the tidal volume contributed by all the other inspiratory extradiaphragmatic muscles during quiet breathing and their share goes up to 1/2 at the highest ventilation. The contribution of the scaleni starts at the same level of inspiratory output found for all extradiaphragmatic muscles and therefore these muscles should not be considered "accessory" Within the range of VT considered the sternomastoids did not appear to contribute, as shown by the fact that their disinsertion did not change the results obtained in spinalized rabbits. Immediately after block of the phrenic nerves there is a marked decrease of VT which then increases within 10-15 breaths to a steady value, three to four times that of the first breath after the paralysis, which is maintained thereafter. The respiratory frequency decreases immediately to a slightly lower value after phrenic block In control animals and does not change when the vagi are cut. In any case a fairly steady value is maintained thereafter even when various types of stimulation are applied. Only changes in body temperature could change respiratory frequency. Chronically phrenicectomized rabbits show some compensatory phenomena either functionally or morphologically. They become able to change their ventilation when chemical drive is increased. In the external intercostal muscles the myoglobin concentration increases and ultrastructural modifications become apparent.

Animals↗

PubMed1993

Effect of phenytoin on acute lung injuries in unanesthetized sheep.

OBJECTIVE: To determine if the intravenous administration of phenytoin attenuates or prevents acute experimental lung injury. DESIGN: Placebo-controlled, longitudinal animal investigative study. SETTING: University research laboratory. SUBJECTS: Sixteen yearling female lambs weighing 30 +/- 3 kg. INTERVENTION: After administration of anesthesia, the animals were endotracheally intubated and mechanically ventilated. Using sterile techniques, four thoracotomies were performed. Through the left fourth intercostal space, cannulas for pressure measurements were inserted directly into the main pulmonary artery and left atrium. An ultrasound flow cuff for determination of cardiac output was placed around the main pulmonary artery. Through the left tenth intercostal space, the diaphragmatic and mediastinal parietal pleura were widely cauterized. Through the right tenth intercostal space, the caudal mediastinal lymph node was identified and divided at the caudal margin of the right pulmonary ligament, and a 1- to 2-cm portion of the node distal to the ligament was resected. The diaphragmatic and mediastinal parietal pleura were widely cauterized. Through the right sixth intercostal space, the efferent duct (or ducts) was identified, ligated at the site of entry into the thoracic duct, and cannulated. The lymph cannula was brought to the outside of the thorax through a separate stab wound. MEASUREMENTS AND MAIN RESULTS: Unanesthetized sheep were studied 7 to 10 days after surgery. Hemodynamic, lung fluid balance, and arterial blood variables were measured in uninjured sheep and in sheep injured by intravenous infusions of Escherichia coli endotoxin (1 microgram/kg iv over 30 mins), air bubbles (0.056 to 0.074 mL/kg/min over 4 hrs), or oleic acid (0.06 mL/kg over 1 hr). The sheep were studied when untreated and after pretreatment with phenytoin. We found that the expected increase in protein-rich lung lymph flow with injuries, resulting from increased microvascular permeability in the lungs, was attenuated by phenytoin when the lungs were injured by endotoxin or air bubbles. In contrast, phenytoin had no effect on oleic acid-induced lung injury or on uninjured lungs. CONCLUSIONS: Phenytoin attenuates acute lung injuries in sheep that are thought to be caused by stimulation of host inflammatory responses (e.g., endotoxin and air bubbles), but has no effect on direct injuries to the lungs (e.g., oleic acid). A plausible mechanism for this finding is phenytoin inhibition of polymorphonuclear leukocyte function.

Animals↗

PubMed2002

Low event rate for stress-only perfusion imaging in patients evaluated for chest pain.

OBJECTIVES: We sought to demonstrate the safety of stress-only perfusion imaging among patients with low to medium probability of coronary disease being evaluated for chest pain. BACKGROUND: The need for performing rest in addition to stress perfusion imaging to confirm normalcy is due largely to defects created on the stress images by attenuation artifacts. A low cardiac event rate among patients undergoing stress-only imaging with attenuation correction (AC) would validate the safety of stress-only imaging. METHODS: Patients with low to medium pretest probability for coronary artery disease (CAD) referred for chest pain evaluation from July 1, 1997 to July 1, 1999, were scheduled for a two-day stress/rest tomographic (single photon emission computerized tomography, or SPECT) perfusion imaging study with Tc-99m sestamibi. Patients were imaged on a variable angle camera with AC using Gd-153 scanning line sources (Vantage ADAC, Milpitas, California). If the stress scan was normal without AC or corrected with AC, the patient did not return for rest scan and was followed. RESULTS: Seven hundred twenty-nine patients underwent stress-only imaging, and follow-up was obtained on 652 (89%) of those patients. There were 224 males and 428 females with mean age of 52 +/- 13 years. Mean follow-up was 22.3 +/- 6.4 months. The mean pretest probability was 37 +/- 24%. The non-AC images showed breast and/or diaphragmatic attenuation artifacts severe enough to have required the patient to return for rest imaging in 37% of patients, and all corrected completely with AC. During follow-up, there were two noncardiac deaths and no cardiac deaths. There was one myocardial infarction; three patients with progressive unstable angina underwent diagnostic coronary angiography showing significant CAD. The overall cardiac event rate was 0.6%. CONCLUSIONS: These results support stress-only imaging in patients with low to medium probability for CAD as a safe, time- and cost-efficient imaging modality.

Adult↗