In vitro posttranslational modification of lamin B cloned from a human T-cell line.

Autoimmune diseases are characterized by spontaneously occurring autoantibodies which have proven to be useful reagents for the characterization of specific nuclear proteins. Using a monoclonal autoantibody (72B9) derived from a murine lupus strain, we have cloned a cDNA from the human T-cell line MOLT-4, which encodes nuclear lamin B. The identity of the encoded protein as lamin B was established by both biochemical and immunological criteria. Inspection of the deduced amino acid sequence of lamin B revealed the presence in coil 1B of the alpha-helical domain of a leucine heptad repeat region. Analysis of mRNA in HL60 and MOLT-4 cells, which express only lamin B, or HeLa cells, which express all three major lamins (A, B, and C), together with the comigration of in vitro-translated product with isolated HeLa cell lamin B by two-dimensional gel electrophoresis, suggests that a single lamin B is expressed in mammalian somatic cells. In vitro translation with the cDNA clone revealed an EDTA-sensitive posttranslational modification which resulted in an increase in the apparent molecular weight to that equivalent to the native in vivo-synthesized lamin B protein. This in vitro modification included incorporation of a product of mevalonolactone and required an intact carboxy terminus.

Antioxidants, oxidative stress, and pulmonary function in individuals diagnosed with asthma or COPD.

OBJECTIVE: The objective of this study was to investigate the association between antioxidant nutrients and markers of oxidative stress with pulmonary function in persons with chronic airflow limitation. DESIGN: Cross-sectional study exploring the association of antioxidant nutrients and markers of oxidative stress with forced expiratory volume in the first second (FEV1%) and forced vital capacity (FVC%). SETTING/SUBJECTS: The study data included 218 persons with chronic airflow limitation recruited randomly from the general population of Erie and Niagara counties, New York State, USA. RESULTS: After adjustment for covariates, multiple linear regression analysis showed that serum beta-cryptoxanthin, lutein/zeaxanthin, and retinol, and dietary beta-carotene, beta-cryptoxanthin, lutein/zeaxanthin, vitamin C, and lycopene were positively associated with FEV1% (P < 0.05, all associations). Serum vitamins beta-cryptoxanthin, lutein/zeaxanthin, and lycopene, and dietary beta-cryptoxanthin, beta-carotene, vitamin C, and lutein/zeaxanthin were positively associated with FVC% (P < 0.05, all associations). Erythrocytic glutathione was negatively associated with FEV1%, while plasma thiobarbituric acid-reactive substances (TBARS) were negatively associated with FVC% (P < 0.05). CONCLUSION: These results support the hypothesis that an imbalance in antioxidant/oxidant status is associated with chronic airflow limitation, and that dietary habits and/or oxidative stress play contributing roles.

Optimization of routine transformation of Escherichia coli with plasmid DNA.

Methods to optimize resources and transformation efficiency of routine daily transformations of DH1 Escherichia coli prepared by three calcium chloride methods were investigated and compared with polyethylene glycol and Hanahan methods. The benefit of a heat-shock step, a preplating incubation step to allow expression of antibiotic resistance, use of log phase bacteria and prolonged storage of bacteria were investigated using pBR322 and pUC18 plasmid DNAs. Bacteria prepared by CaCl2 methods consistently gave efficiencies of 4 x 10(6) transformants/microgram of plasmid DNA or better and were overall the most labor- and resource-efficient methods. Use of log phase bacteria, a heat shock and an incubation step were found to be beneficial for freshly prepared bacteria for all methods. Prolonged storage of up to 30 days of bacteria prepared by the CaCl2 methods was beneficial, resulting in a sustained increase in transformation efficiency when selection was by ampicillin but not when by tetracycline resistance. Also found when using bacteria stored three days or longer was an increased transformation efficiency of stationary vs. log phase bacteria and an unchanged or even increased efficiency when the preplating incubation step was omitted. The Hanahan methods were the most labor and resource intensive and routinely gave efficiencies of 2 x 10(7). Higher efficiencies of 10(8) were obtained only with repeated trial and error and were not consistently reproducible. The polyethylene glycol method consistently gave efficiencies of 2 x 10(7), and bacteria could easily be prepared daily or frozen with a minimal decrease in efficiency.

Validity of neural network in sleep apnea.

Clinical assessment of obstructive sleep apnea (OSA) is poor. Overnight polysomnography (OPG) is the standard reference test, but it is expensive and time-consuming. We developed an artificial neural network (ANN) using anthropomorphic measurements and clinical information to predict the apnea-hypopnea index (AHI). All patients completed a questionnaire about sleep symptoms, sleep behavior, and demographic information prior to undergoing OPG. Neck circumference, height, and weight were obtained on presentation to the sleep center. Twelve variables were used as inputs. The output was an estimate of the AHI. The network was trained with a back-propagation algorithm on 189 patients and validated prospectively on 80 additional patients. Data from the derivation group was used to calculate the 95% confidence interval of the estimated AHI. Predictive accuracy at different AHI thresholds was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic curve. The c-index for predicting OSA in the validation set was 0.96 +/- 0.0191 SE, 0.951 +/- 0.0203 SE, and 0.935 +/- 0.0274 SE, using thresholds of > 10, > 15, and > 20/hour respectively. The actual AHI of the 80 patients in the validation data set fell within the 95% confidence limits of the values predicted by the ANN. This study suggests that ANN may be useful as a predictive tool for OSA.

A comparison of severity of illness scoring systems for critically ill obstetric patients.

STUDY OBJECTIVE: To evaluate the predictive ability of three scoring systems, acute physiology and chronic health evaluation (APACHE II), simplified acute physiology score (SAPS II), and mortality probability models (MPM II) in critically ill obstetric patients compared to a control group of non-obstetric female patients of similar age group (range, 17 to 41 years). DESIGN: A retrospective medical chart review of obstetric and nonobstetric female patients between 17 and 41 years of age. SETTING: Two university hospitals. PATIENTS: Ninety-three obstetric patients and 96 nonobstetric female patients were identified from 12,740 consecutive ICU admissions. RESULTS: The actual mortality of the obstetric and the nonobstetric group was 10.8% (95% confidence interval [CI], 5.3 to 19.0%) and 12.5% (95% CI, 6.6 to 21.0%), respectively. The observed mortality was not statistically different from the mortality predicted by APACHE II, SAPS II, and MPM II (14.7%, 7.8%, and 9.1% for the obstetric group and 10.9%, 9.0%, and 9.9% for the nonobstetric group). Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operator characteristic (ROC) curve. There were no significant differences in the c-index for APACHE II, SAPS II, and MPM II within or between the obstetric group ([mean +/- SE], 0.93 +/- 0.02, 0.90 +/- 0.04, and 0.91 +/- 0.04, respectively) and the nonobstetric group (0.97 +/- 0.02, 0.95 +/- 0.03, and 0.96 +/- 0.02, respectively). CONCLUSIONS: We conclude that APACHE II, SAPS II, and MPM II assess the ICU outcome of critically ill obstetric patients as accurately as nonobstetric critically ill female patients of similar age group.

Clinical suspicion of fatal pulmonary embolism.

BACKGROUND: Less than one third of patients with fatal pulmonary embolism (PE) are identified prior to autopsy. OBJECTIVE: To determine whether the clinical syndromes of acute PE are effective at identifying patients who die of this condition. METHOD: Seven hundred seventy-eight autopsy reports at the Buffalo General Hospital from 1991 to 1996 inclusive were reviewed. Inpatient medical records of 67 patients who were identified as having PE as the primary or major cause of death then were analyzed. RESULTS: Thirty patients (45% [95% confidence interval, 33 to 57%]) had received a diagnosis of PE prior to death, which was marginally higher than the number previously reported (p < 0.05). The diagnosis of PE was significantly lower (13%; p < 0.01) in patients with COPD or coronary artery disease (33%; p < 0.01). In contrast to the prospective investigation of PE diagnosis data, only a minority of patients (6%) presented with pleuritic pain or hemoptysis, while a significantly larger proportion (24%; p < 0.01) of our patients experienced circulatory collapse. Only 55% were identified as having PE from the following clinical syndromes of PE: isolated dyspnea; pleuritic pain and/or hemoptysis; and circulatory collapse. Among the 30 patients suspected of having PE, only 14 (47%) received IV heparin in therapeutic doses, despite clinical suspicion. CONCLUSION: Our results show a modest increase in the correct antemortem diagnosis of fatal PE. The current clinical syndromes used as markers for suspecting PE are not sufficient to detect patients who ultimately die of PE. Physicians should maintain a higher index of suspicion since fatal PE does not always present as one of the three clinical syndromes of PE. Once PE is suspected, heparin therapy should be started early.

Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study.

STUDY OBJECTIVES: Results from several studies have described a relationship between pulmonary function and both all-cause and cause-specific mortality. The purpose of this study was to investigate the predictive value of pulmonary function by gender after 29 years of follow-up. DESIGN: Prospective study with 29-year follow-up of the Buffalo Health Study cohort. PARTICIPANTS: Randomly selected sample of 554 men and 641 women, aged 20 to 89 years, from all listed households of the city of Buffalo, NY. MEASUREMENTS AND RESULTS: Baseline measurements were performed in 1960 to 1961. Pulmonary function was assessed based on FEV(1) expressed as the normal percent predicted (FEV(1)%pred). FEV(1)%pred adjusted by age, body mass index, systolic BP, education, and smoking status was inversely related to all-cause mortality in both men and women (p<0.01). A sequential survival analysis in participants who had a survival time of at least 5, 10, 15, 20, and 25 years after enrollment in the study was also performed. Except for men who survived for > 25 years, we observed a statistically significant negative association between FEV(1)%pred and all-cause mortality. FEV(1)%pred was also inversely related to ischemic heart disease (IHD) mortality. When participants were divided into quintiles of FEV(1)%pred, participants in the lowest quintile of FEV(1)%pred experienced significantly higher all-cause mortality compared with participants in the highest quintile of FEV(1)%pred. For the entire follow-up period, the adjusted hazard ratios for all-cause mortality were 2.24 (95% confidence interval [CI], 1.60 to 3.13) for men and 1. 81 (95% CI, 1.24 to 2.63) for women, respectively. Hazard ratios for death from IHD in the lowest quintile of FEV(1)%pred were 2.11 (95% CI, 1.20 to 3.71) and 1.96 (95% CI, 0.99 to 3.88) for men and women, respectively. CONCLUSIONS: These results suggest that pulmonary function is a long-term predictor for overall survival rates in both genders and could be used as a tool in general health assessment.

Airway inflammation and etiology of acute exacerbations of chronic bronchitis.

STUDY OBJECTIVES: The etiologic role of bacterial pathogens isolated from sputum culture in 40 to 50% of acute exacerbations of chronic bronchitis (AECB) is controversial. If bacterial pathogens cause these AECB, they should be associated with greater neutrophilic airway inflammation than pathogen-negative exacerbations. DESIGN: This hypothesis was tested by comparing levels of interleukin (IL)-8, tumor necrosis factor (TNF)-alpha, and neutrophil elastase (NE) in 81 sputum samples obtained from 45 patients with AECB. Four groups were compared. In the first three groups, nontypable Haemophilus influenzae (n = 20), Haemophilus parainfluenzae (n = 27), and Moraxella catarrhalis (n = 14) were isolated as sole pathogens, respectively. In the fourth group, only normal flora was isolated (n = 20). Paired samples, obtained from individual patients at different times, that differed in their culture results were also compared. SETTING: An outpatient research clinic at a Veterans Affairs Medical Center. PATIENTS: These patients were participating in a prospective, longitudinal study of the dynamics of bacterial infection in chronic bronchitis, for which they were seen in the study clinic on a monthly basis as well as when they were experiencing symptoms suggestive of AECB. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: H influenzae exacerbations were associated with significantly higher sputum IL-8, TNF-alpha, and NE. M catarrhalis exacerbations demonstrated significantly higher sputum TNF-alpha and NE when compared to pathogen-negative exacerbations. H parainfluenzae-associated exacerbations had an inflammatory profile similar to pathogen-negative exacerbations. Sputum elastase level distinguished bacterial from nonbacterial AECB and correlated with clinical severity of the AECB. CONCLUSIONS: Increased airway inflammation associated with isolation of H influenzae and M catarrhalis supports an etiologic role of these pathogens in AECB.

Predicting active pulmonary tuberculosis using an artificial neural network.

BACKGROUND: Nosocomial outbreaks of tuberculosis (TB) have been attributed to unrecognized pulmonary TB. Accurate assessment in identifying index cases of active TB is essential in preventing transmission of the disease. OBJECTIVES: To develop an artificial neural network using clinical and radiographic information to predict active pulmonary TB at the time of presentation at a health-care facility that is superior to physicians' opinion. DESIGN: Nonconcurrent prospective study. SETTING: University-affiliated hospital. PARTICIPANTS: A derivation group of 563 isolation episodes and a validation group of 119 isolation episodes. INTERVENTIONS: A general regression neural network (GRNN) was used to develop the predictive model. MEASUREMENTS: Predictive accuracy of the neural network compared with clinicians' assessment. RESULTS: Predictive accuracy was assessed by the c-index, which is equivalent to the area under the receiver operating characteristic curve. The GRNN significantly outperformed the physicians' prediction, with calculated c-indices (+/- SEM) of 0.947 +/- 0.028 and 0.61 +/- 0.045, respectively (p < 0.001). When the GRNN was applied to the validation group, the corresponding c-indices were 0. 923 +/- 0.056 and 0.716 +/- 0.095, respectively. CONCLUSION: An artificial neural network can identify patients with active pulmonary TB more accurately than physicians' clinical assessment.

Clinical and radiographic manifestations of uncommon pulmonary nontuberculous mycobacterial disease in AIDS patients.

STUDY OBJECTIVE: To determine the clinical and radiographic findings of nontuberculous mycobacteria (NTM) other than Mycobacterium avium complex (MAC) and Mycobacterium kansasii in AIDS compared with non-AIDS patients. DESIGN: A retrospective chart review of all patients in whom NTM other than MAC complex and M kansasii were isolated between April 1, 1989, and October 31, 1995. SETTING: University-affiliated hospital. PATIENTS: Fifty-four patients met the criteria for uncommon pulmonary NTM disease: (1) repeated isolation of atypical mycobacterium in colony counts of > or = 3 from two or more sputum specimens; or isolation of the organism from transbronchial or open lung biopsy specimen with histologic changes suggestive of mycobacterial disease in the absence of other pathogens; and (2) either an abnormal chest radiograph, the cause of which had not been attributed to an active infection other than atypical mycobacterial disease; or the presence of one or more symptoms indicative of pulmonary disease coupled with exclusion of other illnesses with similar symptoms and signs. RESULTS: Thirty-five patients were HIV positive. Fever was the only clinical symptom more commonly seen in HIV-infected patients with NTM than non-HIV-infected patients. Sixty-six percent of all patients with AIDS were infected by Mycobacterium xenopi. Chest radiographs of AIDS patients showed a tendency for predominance of interstitial infiltrate and rarity of fibronodular disease. No specific radiographic pattern was observed for any particular organism. Adenopathy was not a feature of uncommon pulmonary NTM in AIDS, and it should suggest an alternate diagnosis. In two patients, NTM isolation from respiratory specimens preceded dissemination. Six of 8 AIDS patients treated for pulmonary NTM remained alive at the end of the study compared with only 4 of 15 patients who were not treated for pulmonary NTM (p<0.05). CONCLUSIONS: Uncommon NTM isolated from respiratory specimens ought to be considered as serious pathogens in the presence of clinical and radiographic manifestations unexplained by other pathologic processes. Colonization with NTM could precede dissemination. Treatment of uncommon pulmonary NTM disease could possibly confer a survival benefit in AIDS patients.

Application of mortality prediction systems to individual intensive care units.

OBJECTIVE: To evaluate the predictive accuracy of the severity of illness scoring systems in a single institution. DESIGN: A prospective study conducted by collecting data on consecutive patients admitted to the medical intensive care unit over 20 months. Surgical and coronary care admissions were excluded. SETTING: Veterans Affairs Medical Center at Buffalo, New York. PATIENTS AND PARTICIPANTS: Data collected on 302 unique, consecutive patients admitted to the medical intensive care unit. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Data required to calculate the patients' predicted mortality by the Mortality Probability Model (MPM) II, Acute Physiology and Chronic Health Evaluation (APACHE) II and Simplified Acute Physiology Score (SAPS) II scoring systems were collected. The probability of mortality for the cohort of patients was analyzed using confidence interval analyses, receiver operator characteristic (ROC) curves, two by two contingency tables and the Lemeshow-Hosmer chi-square statistic. Predicted mortality for all three scoring systems lay within the 95 % confidence interval for actual mortality. For the MPM II, SAPS II and APACHE II, the c-index (equivalent to the area under the ROC curve) was 0.695 +/- 0.0307 SE, 0.702 +/- 0.063 SE and 0.672 +/- 0.0306 SE, respectively, which were not statistically different from each other but were lower than values obtained in previous studies. CONCLUSION: Although the overall mortality was consistent with the predicted mortality, the poor fit of the data to the model impairs the validity of the result. The observed outcome could be due to erratic quality of care, or differences between the study population and the patient population in the original studies. The data cannot be used to distinguish between these possibilities. To increase predictive accuracy when studying individual intensive care units and enhance quality of care assessments it may be necessary to adapt the model to the patient population.

Compliance of the main pulmonary artery during the ventilatory cycle.

Transmural pulmonary arterial pressure (Ppa), diameter (D), and length (L) of a segment of the main pulmonary artery (MPA) were measured simultaneously in anesthetized open-chest dogs. The instantaneous volume was calculated from D and L. Pulmonary arterial elasticity for diameter (EpD) was calculated as the ratio of the amplitude of Ppa to D oscillation normalized by the mean D. Similar indexes were calculated for L (EpL) and V (Epv). Compliance per unit length was calculated from the dimensions and elasticity of the MPA. Under control conditions with 5 cmH2O positive end-expiratory pressure, EpD, EpL, and Epv at cardiac frequency were 175 +/- 27, 147 +/- 27, and 55 +/- 7 cmH2O, respectively. EpD increased with positive end-expiratory pressure, but EpL decreased and Epv was unaffected. EpD, EpL, Epv, and compliance per unit length were not significantly different between the start of inspiration and the start of expiration. In addition, there were no significant phase differences between the oscillations of Ppa and V at respiratory frequency. We conclude that the previously reported time variation of pulmonary arterial compliance during the ventilatory cycle is not due to time-varying properties of the MPA.

Dynamic response of local pulmonary blood flow to alveolar gas tensions: experiment.

The purpose of this study was to investigate the mechanism that causes a damped oscillatory response of local pulmonary blood flow to local hypoxia. The left lower lobe (LLL) of 10 anesthetized dogs was ventilated independently but synchronously with the rest of the lungs. Blood flow to the LLL as a proportion of total flow (QLLL/QT) was measured during the on-transient of the hypoxic response when LLL inspirate was changed from O2 to N2. There was a damped oscillatory response of QLLL/QT to hypoxia (34 of 40 trials). In contrast, the off-transient was always monotonic. There was no enhancement of the steady state or dynamic hypoxic response with repeated challenges. Local alveolar hypercapnia caused a damped oscillatory response in the presence of local hypoxia (15 of 20 trials), but there was no response in the presence of local hyperoxia. We conclude that 1) the dynamic pulmonary vascular response to O2 and CO2 are not additive because the response to CO2 is attenuated by hyperoxia and 2) the damped oscillatory response that occurs during hypoxia is the result of changes of local alveolar CO2 per se.

Time-varying pulmonary arterial input impedance via wavelet decomposition.

Wavelet decomposition is proposed as a novel approach for determining pulmonary arterial input impedance throughout the breathing cycle. The canine pulmonary arterial input impedance was evaluated throughout the ventilatory cycle at 5, 10, and 15 cmH2O of positive end-expiratory pressure. The impedance spectrum was obtained by Fourier transformation of wavelets generated by decomposing the pulmonary arterial pressure and flow waveforms. With wavelet decomposition, each heart beat is viewed individually as a transient pulse rather than as an interval within a continuous function of pressure and flow. The advantage of using this approach is the ability to obtain stable estimates of input impedance spectra with high-frequency resolution over the entire frequency range with only a limited data set of pressure and flow decomposed to wavelets as short as singular extrapolated cardiac cycles. This method was used to define the changes of input impedance that occur during the ventilatory cycle. Results show that the impedance spectrum undergoes notable changes during the breathing cycle and demonstrate the utility of the proposed method.

Beat-by-beat changes of viscoelastic and inertial properties of the pulmonary arteries.

We tested the hypothesis that pulmonary arterial input impedance varies during the ventilatory cycle due to alterations not only of the viscoelastic components of the pulmonary vasculature but also due to changes of the inertial components. A four-element lumped-parameter model was used to fit the pulmonary arterial pressure-flow recordings in the time domain in 10 anesthetized dogs. The four elements consisted of a resistor (R) that represents input resistance, a second resistor (R1) and a capacitor (C1) that represent the viscoelastic properties of the pulmonary vasculature, and an inductor (L1) that represents inertial properties of blood within the pulmonary vasculature. The parameters were evaluated at each heartbeat throughout the ventilatory cycle at three levels of positive end-expiratory pressure. All four parameters varied significantly during the ventilatory cycle. R, C1, L1, and R1 varied by up to 97, 33, 13, and 17%, respectively. Changes in parameter values were most apparent at the start of expiration when the most rapid changes of lung volume occur. This pattern of the results is consistent with the hypothesis that the time variation of pulmonary arterial impedance is due to dynamic shifts of blood volume between the extra-alveolar and alveolar arteries.

Pulmonary arterial elasticity in awake dogs.

We measured the relationship between pulmonary arterial pressure (Ppa), diameter (D), and length of a segment of the main pulmonary artery (MPA) in chronically instrumented conscious dogs breathing spontaneously (CCC). There were no physiologically significant changes in Ppa or D in the CCC dogs postoperatively, and the cross-sectional MPA shape measured by fast computed tomography was nearly circular. These results suggest that the MPA was not distorted by chronic instrumentation. We compared measurements made in the CCC dogs with previous measurements in acutely instrumented anesthetized dogs with open chests (AAO). The elasticity of MPA in the CCC animals was frequency dependent between 1 and 14 Hz and was similar to that in the AAO dogs. Oscillations of D preceded Ppa at cardiac frequencies in the AAO animals, but the D and Ppa oscillations were in phase in the CCC animals. The oscillations of length relative to D were significantly less in the CCC than in the AAO dogs. We conclude that, with limitations, the hemodynamic properties of the MPA can be measured in the CCC subjects. We suggest that the discrepancies between the AAO and CCC dogs can be attributed to differences in extrinsic loading of the MPA.

Time-varying pulmonary arterial compliance.

We tested the hypothesis that pulmonary arterial compliance (Ca) varies during the ventilatory cycle. Pressure and flow in the main pulmonary artery were measured in open-chest dogs under chloralose anesthesia (n = 12) with a positive-pressure volume-cycled ventilator. Input impedance was calculated from the pressure and flow waves of heart cycles obtained immediately after the start of inspiration (SI) and immediately after the start of expiration (SE). A lumped parameter model was used to calculate Ca from the input impedance spectrum of the main pulmonary artery. Three levels of positive end-expiratory pressure (PEEP) were used before and after meclofenamate (n = 6) or vagotomy (n = 6). Ca was significantly greater at SE than at SI at each level of PEEP. PEEP increased Ca at SE but not at SI. None of these changes was altered by meclofenamate or vagotomy, suggesting that these differences of Ca were due to passive mechanical effects rather than an active neurohumoral mechanisms. We conclude that Ca is time varying during the ventilatory cycle because it is altered by the dynamic increase of lung volume between SI and SE, but not with the quasi-static increase of lung volume induced by raising the level of PEEP. These changes of Ca were unaffected by vagal feedback or inhibition of cyclooxygenase. We suggest that the increased Ca just after the start of expiration may result from dynamic shifts of blood volume from the extra-alveolar to the alveolar vessels.

Effect of perivascular electromagnetic flow probes on pulmonary hemodynamics.

We determined the effect of perivascular electromagnetic flow probes (EMF) on pulmonary hemodynamics in acute experiments. In seven dogs placement of the EMF on the main pulmonary artery (MPA) increased pulmonary arterial pulse pressure by 25% (17.8-21.9 cmH2O, P less than 0.005) and mean right ventricular pressure by 12% (23.2-25.9 cmH2O, P less than 0.001) but did not alter heart rate, systemic blood pressure, mean pulmonary arterial pressure, or right ventricular end-diastolic pressure. This response was not abolished by local application of lidocaine to the MPA. In three cats input impedance was calculated from measurements of pressure and flow in the MPA. Impedance was calculated with flow measured using an EMF and ultrasonic volume flow probe (USF), which avoids the constraining effect of the EMF. When flow was measured with an EMF rather than a USF, there was a significant difference in the impedance spectra (P less than 0.001), but it was only apparent in the moduli greater than six harmonics. We conclude that the EMF does affect right ventricular afterload in acute experiments and alters the measured input impedance.

Air transportation of patients with acute respiratory failure: theory.

Adult respiratory distress syndrome (ARDS) that results from severe trauma often occurs in remote places, making it necessary to transport the patients to tertiary medical facilities by air. Since these severely hypoxic patients are exposed to additional risk of reduced inspired oxygen tension due to decreased barometric pressure, the feasibility of transportation of these patients was investigated by computer analysis. Mathematical models of pulmonary gas exchange in patients with ARDS were developed to calculate arterial and mixed venous blood tensions while breathing room air and oxygen at sea level, 8,000 ft, and 40,000 ft. Under each condition the following parameters were varied: alveolar ventilation (VA), cardiac output (Q), metabolic rate (VO2), hematocrit (Hcrit), and membrane diffusing capacity for oxygen (DmO2). Most of the gas exchange problems at altitude could be overcome by breathing oxygen as long as cardiac output and hematocrit were adequate. Hypoxemia in ARDS patients will not be greatly affected by the reduced inspired oxygen tensions at altitude in much the same way that hypoxemia in ARDS is poorly responsive to increased inspired oxygen tensions at sea level.

Ventilatory criteria for aeromedical evacuation.

Ventilatory requirements during simulated aeromedical transportation were investigated in normal dogs and animals with oleic acid-induced lung injury. Inspired oxygen fractions of 0.21 and 1.0 were used to ventilate the normal and injured dogs, respectively. Both groups were ventilated with a constant-volume piston ventilator. After a control period, animals were exposed to a simulated altitude of 8,000 ft (barometric pressure 564 mm Hg), followed by a second control period at ground level. Both groups of animals had no change in carbon dioxide production, arterial PCO2 or ventilation during exposure to reduced barometric pressure. Systemic blood pressure, heart rate, cardiac output, and lung volume were all lower in oleic acid-injured animals than controls; the alveolar-arterial oxygen difference was larger in the oleic acid group. With altitude exposure, arterial and mixed venous oxygen tensions were decreased in both groups. Adequate gas exchange can be maintained during exposure to altitude even in animals with abnormal function provided that ventilation is constant and the inspired oxygen fraction is increased to compensate for the reduced barometric pressure.