Does the intensity of daily walking matter for protecting against the development of a slow gait speed in people with or at high risk of knee osteoarthritis? An observational study.

OBJECTIVE: Knee osteoarthritis (OA) is a risk factor for a decline in gait speed. Daily walking reduces the risk of developing slow gait speed and future persistent functional limitation. However, the protective role of walking intensity is unclear. We investigated the association of substituting time spent not walking, with walking at light and moderate-to-vigorous intensities for incident slow gait over 2-years, among people with or at high risk of knee OA. METHOD: We used baseline and 2-year follow-up data from the Multicenter Osteoarthritis (MOST) study (n = 1731) and the Osteoarthritis Initiative (OAI, n = 1925). Daily walking intensity was objectively assessed using accelerometer-enabled devices, and classified as; not walking (<1 steps/min), very-light (1-49 steps/min), light (50-100 steps/min), and moderate-to-vigorous (>100 steps/min). We defined slow gait during a 20-m walk, as <1 m/s and <1.2 m/s. Isotemporal substitution evaluated time-substitution effects on incident slow gait outcomes at 2-years. RESULTS: Replacing 20 min/day of not walking with walking at a moderate-to-vigorous intensity, demonstrated small to moderate reductions in the risk of developing a gait speed <1.0 m/s (Relative Risk [95% confidence interval (CI)]; MOST = 0.51 [0.27, 0.98], OAI = 0.21 [0.04, 0.98]), and <1.2 m/s (MOST = 0.73 [0.53, 1.00], OAI = 0.65 [0.36, 1.18]). However, only risk reductions for <1.0 m/s met statistical significance. Replacing not walking with very-light or light intensity walking was not associated with the risk of developing slow gait outcomes. CONCLUSION: When possible, walking at a moderate-to-vigorous intensity (>100 steps/min) may be best recommended in order to reduce the risk of developing critical slow gait speed among people with, or at high risk of knee OA.

Accuracy of injection and short-term pain relief following intra-articular corticosteroid injection in knee osteoarthritis - an observational study.

BACKGROUND: Intra-articular corticosteroid injections (IACI) are effective treatments for pain in knee osteoarthritis (KOA) but treatment response varies. There is uncertainty as to whether structural factors such as accurate placement of IACI affect outcome. We examined this question in a pragmatic observational study, using ultrasound (US) to verify accuracy of IACI. METHODS: 105 subjects with KOA (mean age 63.1 years, 59% female) routinely referred for IACI underwent assessment of demographic factors, x-ray and US of the knee before aspiration and IACI (based on clinical landmarks) with 40 mg triamcinolone acetonide with lignocaine plus a small amount of atmospheric air by an independent physician. US demonstration of intra-articular mobile air, i.e. a positive air arthrosonogram, was used to determine accurate placement of injection. Both patients and injecting physicians were blind to the US findings. Pain at baseline, three and nine weeks post injection was assessed using the 500 mm WOMAC pain subscale and response defined as ≥ 40% reduction in pain from baseline. Inter-observer reliability of air-arthrosonogram assessment was good: κ 0.79 (three raters). RESULTS: Sixty-three subjects (60.6%) were responders at three weeks and 43 (45.7%) at nine weeks. Seventy-four subjects (70.5%) had a positive arthrosonogram. A positive air arthrosonogram did not associate with a higher rate of response to treatment (p 0.389 at three weeks, p 0.365 at nine weeks). There was no difference in US effusion depth, power Doppler signal or radiographic grade between responders and non-responders to the injection, but female gender associated with response at 3 weeks and previous injection with non-response at 9 weeks. CONCLUSIONS: Accurate intra-articular injection of corticosteroid results did not result in superior outcome in terms of pain compared to inaccurate injection in symptomatic knee OA.

Serum uric acid is independently associated with hypertension in patients with rheumatoid arthritis.

Hypertension (HT) is highly prevalent in rheumatoid arthritis (RA). Serum uric acid (SUA) has been associated with HT in the general population. The mutual exclusion of gout and RA, and the systemic inflammatory component of RA may alter this association in this patient population. We explored a potential association between SUA levels and HT in RA and evaluated whether this association is independent of HT risk factors, RA characteristics and relevant drugs. A total of 400 consecutive RA patients were assessed. SUA and complete biochemical profile were measured. Demographic, HT-related factors, RA characteristics and drugs were assessed as potential covariates. Results were analysed using binary logistic models to test the independence of the association between SUA and HT. SUA levels were higher in hypertensive compared to normotensive RA patients (5.44+/-1.6 mg dl(-1) (323.57+/-95.17 micromol l(-1)) vs 4.56+/-1.1 mg dl(-1) (271.23+/-65.43 micromol l(-1)), P<0.001). When adjusted for HT risk factors, renal function, RA characteristics, non-steroidal anti-inflammatory drugs, oral prednisolone, cyclosporine, leflunomide and low-dose aspirin, the odds of being a hypertensive RA patient per 1 mg dl(-1)(59.48 micromol l(-1)) SUA increase were significantly increased: OR=1.59 (95% CI: 1.21-2.1, P=0.001). This was also significant for the subgroup of patients who were not on diuretics (OR=1.5, 95% CI: 1.1-2.05; P=0.011). This cross-sectional study suggests that SUA levels are independently associated with HT in RA patients. Prospective longitudinal studies are needed to confirm and further explore the causes and implications of this association.

Therapeutic angiogenesis for peripheral artery disease: cytokine therapy.

In recent years the importance of circulating bone marrow-derived cells in angiogenesis and collateral growth has been demonstrated in peripheral artery disease (PAD) and other ischaemic diseases. Although the mechanisms by which these cells exert their angiogenetic/arteriogenetic effects are not completely understood, improving the accumulation of bone marrow-derived cells at the site of vascular growth using cytokines has become one aim in some of the regenerative therapies. Interestingly recent data indicate that in addition to effects attributed to such accumulated cells there are also direct effects of cytokines used via their receptors. Several investigations in animal hind limb models of ischaemia have demonstrated the beneficial effect of bone marrow mobilisation using colony-stimulating factors (CSF) on collateral growth and perfusion recovery. Clinical studies in PAD patients, however are still rare and led to inconsistent data, in part due to different application protocols, choice of cytokine and low patient numbers with strong placebo effects. Moreover; the aetiology of the disease in humans differs markedly from the artificial occlusion of the femoral artery in a mostly healthy animal in the preclinical setting. Another approach to enhance arteriogenesis, which has been successful in animal models of hind limb ischaemia, is the local injection of the monocyte chemoattractant protein 1 (MCP-1). This treatment stimulated the invasion of monocytes leading to improved collateral growth and restoration of limb perfusion. Recent reports from animal experiments, in which both treatment strategies were combined (i.e. bone marrow mobilisation and enhancement of cell migration to the site of vascular growth), have shown strong synergistic effects, pointing at the importance to orchestrate the different processes involved in vascular repair in order to achieve maximal therapeutic effects.

[Treatment of hypertension in daily practice. Current results of a postmarketing surveillance study with telmisartan]. / Die Therapie der Hypertonie in der täglichen Praxis. Aktuelle Ergebnisse einer Postmarketing-Surveillance-Studie mit Telmisartan.

AIM: Evaluation of efficacy and tolerability of telmisartan monotherapy and telmisartan plus hydrochlorothiazide in daily practice. METHODS: Patients with arterial hypertension were included in this non-interventional, observational study. Demographic data, medical history, therapy with telmisartan and telmisartan plus hydrochlorothiazide as well as blood pressure and heart rate at 0, 4, 8, and 12 weeks were recorded by 1211 physicians. Moreover, overall efficacy and tolerability were assessed. Adverse events and adverse drug reactions were documented. RESULTS: Out of 6319 patients 52.9% were male. Mean age was 59.9 years and mean body mass index (BMI) was 27.8 kg/m2. 70% of patients had grade 2 or 3 hypertension, 59% had a high or very high additional cardiovascular risk. In 34.6% of patients hypertension was newly diagnosed, while the remaining 65.4% had been hypertensive for an average of 7.2 years. 3386 patients initially received telmisartan (54%: 40 mg; 45.4%: 80 mg). 2928 patients were given telmisartan plus hydrochlorothiazide (56.9%: 80/12.5 mg; 43.1%: 40/12.5 mg). In 69.8% of the patients the dose remained unchanged throughout the study. The remaining patients were either given a higher dose or changed over to the combination. Under treatment, the systolic and diastolic blood pressures decreased by an average of 28.5 mmHg and 14.1 mmHg, respectively. Mean pulse pressure decreased by 14.4 mmHg. The efficacy of the treatment was assessed "very good" or "good" in 94.2% of all patients, and tolerability in 98.8%. Adverse events occurred in 43 (0.7%) patients, and adverse drug reactions in 28 (0.4%) patients. CONCLUSION: Under daily practice conditions telmisartan monotherapy and telmisartan plus hydrochlorothiazide are very effective and well tolerated. Systolic and diastolic blood pressure as well as pulse pressure are effectively lowered.

Exploring the mammalian neuromuscular system by analysis of mutations: spinal muscular atrophy and myotonia.

Any biological structure can be studied using mutations that interfere either with its emergence or its function. We investigate spontaneous and induced mutations in the mouse that affect neuromuscular development and function. The wobbler mouse (phenotype WR, genotype wr/wr) suffers from muscular atrophy because of the degeneration of 20-40% of the motoneurones; it is also unable to produce functional spermatozoa. As a step towards positional cloning of the wr gene, we have mapped the locus to proximal chromosome 11, thus excluding CNTF and its receptor as candidates, and suggesting the closely-linked Rab 1 gene encoding a GTP-binding protein as a possibility. In the case of the adr (arrested development of righting response) mouse, which shows hyperexcitability of mature muscle fibres due to a reduction of the 'dampening' function of chloride conductance at resting potential, we have shown that the defect is in the chloride channel gene adr/Clc-1 on chromosome 6. This allowed us to predict via synteny the chromosomal location of human Thomsen's and Becker's myotonias as close to the TCRB gene on human chromosome 7q. The combination of these approaches with gene-targeting approaches will allow genetic analysis of the establishment and structure of the neuromuscular system.

Hydroxyl ion movements across the human erythrocyte membrane. Measurement of rapid pH changes in red cell suspensions.

A stopped flow rapid reaction apparatus capable of following changes of +/-0.02 pH unit in 0.1 ml of solution in less than 0.005 sec has been developed, utilizing a commercially available pH-sensitive glass electrode. Using this instrument, extracellular pH at 37 degrees C was followed from less than 0.025 sec to 300 sec after mixing equal volumes of the following CO(2)-free solutions: (A) normal human red cells, washed three times and resuspended in 150 mM NaCl at pH 7.2 with a hematocrit of 18%; and, (B) 150 mM NaCl adjusted with HCl or NaOH to pH 2.1 to pH 10.3. A minimum of 2 ml of mixture had to flow through the electrode chamber to ensure complete washout. The mixing process produced a step change in the pH of the extracellular fluid, after which exchanges across the red cell membrane and buffering by intracellular hemoglobin caused it to return toward pH 7.2 with an approximately exponential time course. Under the assumption that pH changes after mixing represent exchanges of hydroxyl for chloride ions across the cell membrane, hydroxyl ion permeabilities (P(OH) (-) in cm/sec) were calculated and found to vary from 2 x 10(-4) at pH 9 to 4 x 10(-1) at pH 4 according to the empirical relationship P(OH) (-) = 170 exp (-1.51 pH). The form of the dependence of P(OH) (-) on extracellular pH does not appear compatible with a simple fixed charge theory of membrane permselectivity.

Inactivation of xanthine oxidoreductase is associated with increased joint swelling and nitrotyrosine formation in acute antigen-induced arthritis.

OBJECTIVE: Arthritis is associated with increased articular formation of nitrotyrosine, which may contribute to injury. Nitrotyrosine is formed by nitration of tyrosine by reactive nitrogen species such as peroxynitrite, the formation of which may be enhanced by xanthine oxidoreductase (XOR), since it can generate nitric oxide from nitrite/nitrate, and superoxide during xanthine metabolism. We hypothesized that inactivation of XOR would protect against antigen-induced arthritis (AIA) and decrease nitrotyrosine formation. METHODS: AIA was induced with methylated bovine serum albumin (mBSA) in three groups of Wistar rats: animals fed on (1) tungsten-enriched chow (0.7 g/kg) (TG), which inactivates XOR, (2) standard chow (SG), and (3) rats treated with allopurinol (50 mg/kg/day; p.o.) (AG). Nitrotyrosine in patella-synovium was quantified by mass spectrometry three weeks after intra-articular (i.a.) antigen injection. RESULTS: Treatment with tungsten, but not allopurinol, suppressed plasma and articular XOR activity at < or = 0.9% of normal levels. XOR inactivation was associated with increased knee swelling 24-48 hrs post i.a. mBSA, compared with controls (mean increase +/- SEM of knee diameter from baseline of 3.3 +/- 0.5, 2.0 +/- 0.3 and 1.9 +/- 0.2 mm in TG, SG and AG (n = 14 each group), respectively; p < 0.05, TG vs SG, ANOVA). Mean ratio of articular nitrotyrosine-tyrosine (+/- SEM) was increased in the XOR-inactivated group, compared with controls: 12.3 +/- 0.7, 9.6 +/- 0.8 and 10.4 +/- 0.5 pg/microg in TG, SG and AG, respectively; p < 0.05, TG vs SG. CONCLUSION: Contrary to expectation, XOR inactivation was associated with increased joint swelling and articular tyrosine nitration in acute AIA, suggesting a novel, protective role for XOR in inflammatory arthritis.

Expression of the potassium channel KV3.4 in mouse skeletal muscle parallels fiber type maturation and depends on excitation pattern.

We report the detailed expression pattern of the voltage-dependent potassium channel KV3.4 (rat homologue, Raw3) in mouse skeletal muscle. Using semi-quantitative RT-PCR, we show that its expression is detectable at embryonic day 17 and rises to adult levels within 2 weeks after birth. Expression is fiber type-dependent, with mRNA levels being 5-6-fold lower in the mixed slow/fast soleus muscle than in the fast tibialis anterior and extensor digitorum longus muscles. Fast muscles from myotonic mice exhibit low KV3.4 mRNA levels similar to those of wild-type soleus. In denervated extensor digitorum longus, KV3.4 expression declines to perinatal levels. We conclude that KV3.4 expression in mouse skeletal muscle is regulated by the pattern of excitation.

Development of electrical myotonia in the ADR mouse: role of chloride conductance in myotubes and neonatal animals.

In the ADR mouse, the homozygous condition of the autosomal mutation adr, "arrested development of righting response", leads to the symptoms of myotonia. The adr mutation is caused by an insertion of a retroposon into a gene for a chloride channel (adr = Clc-1) that is expressed in adults, but only at very low levels in neonate rodent muscle. In the present study, we investigated the earliest stages of the ADR myotonia. In muscle from 7-day-old ADR mice that can be recognized by inspection, electrical after-activities are distinct by their low frequency (1-5 Hz) and long duration (several minutes) from those recorded in adult muscle. Similar myotonic symptoms could be evoked in muscle fibres from 7 day wildtype mice after substitution of the external chloride with impermeant anions or by activators of protein kinase C. The genotypes of 3-day-old mice cannot be inferred from inspection and, thus, were identified by Southern blotting with a ClC-1 probe. Although no +/+ animal showed characteristic myotonic series, these were seen both in adr/adr and in most adr/+ animals. Thus, due to the low dosage of chloride channels in 3-day-old mouse muscle, the adr mutation appears to be partially dominant rather than fully recessive, as in adult mice. No indication of electrical myotonia could be demonstrated in cultured myotubes, although their pattern of excitability depended on the presence of external chloride ions. We conclude that the low Cl(-)-conductance of myotubes influences excitability but is not controlled by the adr/Clc-1 gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Application of cDNA arrays to monitor mRNA profiles in single preimplantation mouse embryos.

Array technology is a widely used tool for gene expression profiling in various biological systems. However, the application of this method to mammalian preimplantation embryos is limited by the small amount of mRNA that can be extracted from a single embryo, which is not sufficient for array analysis. Here we report a protocolfor the rapid global amplification of embryonic mRNA that permits the generation of expression profiles from single murine blastocysts. The approach combines global PCR and 77 RNA polymerase amplification and allows the preparation of labeled, amplified RNA for array hybridization from single murine blastocysts containing approximately 1.5 pg mRNA in less than 12 h. We demonstrate that this amplification procedure is highly reproducible and does not bias original relative mRNA levels. Signal patterns from various embryonic stages of murine development revealed marked differences in mRNA expression that were in accordance with previously published data. We found genes known to be involved in embryonic apoptosis expressed at different levels in individual murine day 3.5 blastocysts. This technique can thus be used to assess embryonic viability and investigate molecular mechanisms of embryonic development.

Oxygen-related intrapulmonary shunting in obstructive pulmonary disease.

A simple and previously validated double-indicator technique was used to quantitate shunt in patients with obstructive pulmonary disease at rest, during exercise, and during breathing of 100 percent oxygen. The method avoids several inherent difficulties encountered in previous double-indicator techniques and is independent of the fraction of oxygen in the inspired gas. Sixteen resting patients with mild obstructive pulmonary disease were found to have intrapulmonary shunting less than or equal to 0.7 percent of the cardiac output (mean, 0-3 +/- 0.2 percent [SD]). During submaximal exercise, shunting was also low (mean, 0.3 +/- 0.1 percent of cardiac output). After breathing pure oxygen for 30 minutes, 11 patients had similar results; however, in four patients, breathing 100 percent oxygen caused an increase intrapulmonary shunting to 1 to 6 percent of the cardiac output. It is concluded that some patients with obstructive pulmonary disease develop intrapulmonary shunting in response to breathing oxygen.

Increased susceptibility to the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone in transgenic mice overexpressing c-myc and epidermal growth factor in alveolar type II cells.

PURPOSE: As previously described, SPC/myc transgenic mice developed bronchioloalveolar adenocarcinomas derived from alveolar type II (AT II) cells within 10-14 months, whereas SPC/IgEGF transgenic mice developed hyperplasias. Our purpose was to determine the potential interplay of environmental and genetic factors in lung tumorigenesis. MATERIALS AND METHODS: Six-week-old SPC/myc and SPC/IgEGF transgenic mice, overexpressing c-myc and a secretable form of the epidermal growth factor (IgEGF) under the control of the surfactant protein C (SPC) promoter, were treated with a single dose of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). As control groups, SPC/myc and SPC/IgEGF transgenic mice were treated with NaCl and non-transgenic littermates were treated with NNK or NaCl, respectively. RESULTS: After 6 months, none of the NaCl-treated transgenic littermates showed bronchioloalveolar hyperplasia and adenocarcinoma formation, whereas 100% of the NNK-treated SPC/myc transgenic mice did. The effect of NNK on SPC/IgEGF transgenic mice was less pronounced, inducing hyperplasia in the lung in only 16.7% of them. In 90% of the NNK-treated non-transgenic littermates no neoplastic changes were detected in the lung. CONCLUSIONS: These results demonstrate that the progression of pulmonary bronchioloalveolar adenocarcinomas, induced by expression of c-myc as a transgene, was accelerated by NNK, suggesting that c-myc cooperates with NNK-induced mutations.

Kinetic measurements of gas exchange in the intact pulmonary microcirculation.

The kinetics of gas exchange are monitored in an isolated perfused lung preparation contained within a plethysmograph. The lungs are perfused with buffer, and there is no gas exchange until a 2.0-ml bolus of reactant is injected into the perfusion system. Subsequent gas exchange produces a pressure transient that is related to the corresponding volume of exchanged gas. The observed rate of volume change is the result of two separate processes: 1) the rate of gas exchange during transit through the capillary bed and 2) the distribution of vascular transit times between the point of injection and the capillary bed. The latter is assessed by a control injection containing a dissolved inert gas that is liberated in the alveoli as the bolus enters the capillary bed. Analysis of the experimental curves permits the separation of these two processes. A model of exchange kinetics indicates that this method has the capability of measuring kinetic events occurring during gas exchange in the microcirculation under physiological conditions.

Influence of carbon dioxide kinetics on pulmonary carbon dioxide exchange.

In the absence of erythrocytes, carbonic anhydrase (CA) localized to the pulmonary capillary endothelium catalyzes the dehydration of bicarbonate to CO2. We studied the effects of lung CA and the reactions of CO2 on CO2 excretion in isolated lungs perfused with buffer. In indicator-dilution experiments, recoveries of dissolved CO2 and acetylene (C2H2) in the venous effluent were delayed significantly compared with a vascular indicator because the gases were distributed in both the vascular and alveolar volumes. In a second group of experiments, the kinetics of CO2 excretion were monitored with a plethysmographic method after injection of a bolus containing dissolved CO2 or bicarbonate. Exchange was compared with excretion of dissolved C2H2. The rate of excretion of dissolved CO2 and C2H2 was identical, indicating that CO2 is exchanged in the same manner as an inert gas. When bicarbonate was injected, CO2 excretion lagged behind C2H2 excretion by approximately 0.3 s. Inhibition of lung CA with acetazolamide reduced the quantity of CO2 exchanged to one-fourth of control and decreased the delay in exchange by one-half.

Influence of cardiac action on gas mixing in closed-chest dogs.

We performed single-breath tests in closed-chest, paralyzed, and anesthetized dogs (6 with bilateral vagotomy and 6 with intact vagi) with the heart beating and during cardiac arrest. Repeated cardiac arrest was achieved by ventricular fibrillation and subsequent defibrillation. Twenty-four single-breath tests per dog were performed in combinations of three inspiratory volumes (VI; 0.2, 0.5, and 0.8 liter) and four postinspiratory pauses (0, 5, 10, and 30 s), either with or without cardiac arrest. The test gas contained four inert relatively insoluble gases (He, Ne, Ar, and SF6) with a sixfold range in diffusivity. Series dead space (VD) decreased with increasing postinspiratory pause, increasing gas diffusivity, or decreasing VI. In vagotomized animals, VD was smaller with the heart beating than during cardiac arrest, but this relationship was reversed in animals with intact vagi. The decrease in VD due to cardiogenic mixing accounted for only 10.8% of the total decrease in VD occurring during a 30-s postinspiratory pause. The slope of phase III decreased with increasing postinspiratory pause except at VI of 0.2 liter. No significant differences were noted in the slope of phase III between experiments performed with the heart beating or arrested. Tracer gas retained in the residual volume after expiration increased with increasing inspiratory pause. Gas retention was greater for He than for SF6 but was not affected by cardiac action. These findings indicate that cardiac action mainly affects the interface between inspired and alveolar gas and has little effect on mixing in the alveolar compartment.

Outpatient oxygen therapy.

Patients with polycythemia, pulmonary hypertension, or cor pulmonale are most likely to benefit from home oxygen therapy; in others, exercise tolerance can be improved and neuropsychologic effects of hypoxemia relieved. Indications for home therapy, methods of delivering outpatient oxygen, economic considerations, and possible complications are addressed.

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.

[Hemodynamics and differentiated CO transfer following fulminant lung embolism and pulmonary artery embolectomy and following recurrent lung embolism]. / Hämodynamik und differenzierter CO-Transfer nach fulminanter Lungenembolie und Pulmonalisembolektomie sowie nach rezidivierenden Lungenembolien.

Pulmonary embolectomy as an emergent surgical treatment after massive pulmonary embolism often is necessary in cardiogenic shock (CS) and even without previous diagnostic. If complete dissolution of the thromboembolus is possible or spreading of microemboli may occur is unknown. Therefore we studied 21 patients surgically treated by embolectomy, ten of these with consecutive cardiogenic shock (CS) and twelve patients after repetitive microembolism and cava-blocking. Besides lung-functional parameters for special CO-diffusion capacity (DLCO), differentiated in membrane (DM) and vascular (VC) component (Roughton and Forster), we measured mean pulmonary artery pressure (PAP) at rest and at exercise. Patients after repetitive embolism showed considerably more diminution of DLCO (-31%) than those after single massive embolic event (-15%) even concomitant by CS (-10%). Repetitive microembolism lowered VC by 21%. Slight decrease of DM was found after CS. Mean pulmonary artery pressure was elevated at rest (26 mm Hg) and exercise (33 mm Hg) after repetitive microembolism and normal after massive embolism or CS. Pulmonary embolectomy may prevent disturbances of DLCO or PAP even after CS. Damage of vascular integrity (VC) was found after microembolism. Pulmonary embolectomy seems to remove total embolic material and therefore seems to be optimal.