Comparison of office, home and ambulatory blood pressure measurements in hypertensive and suspected hypertensive SWICOS participants.

PURPOSE: Hypertension should be confirmed with the use of home BP measurement (HBPM) or 24h ambulatory BP measurement (ABPM). The aim of our study was to compare measurements obtained by OBPM, HBPM and ABPM in individuals with elevated OBPM participating in the population-based Swiss Longitudinal Cohort Study (SWICOS). MATERIAL AND METHODS: Participants with OBPM ≥140/90 mmHg assessed their BP using HBPM and ABPM. The cut-off for hypertension was ≥135/85 mmHg for HBPM, ≥130/80 mmHg for ABPM. White-coat hypertension (WCH) was defined as normal HPBM and ABPM in participants not taking antihypertensive drugs. Uncontrolled hypertension was defined as hypertension in HBPM or ABPM despite antihypertensive treatment. RESULTS: Of 72 hypertensive subjects with office BP ≥140/90 mmHg and valid measurements of HBPM and ABPM, 39 were males (aged 62.8 ± 11.8y), 33 were females (aged 57.4 ± 14.2y). Hypertension was confirmed with HBPM and ABPM in 17 participants (24%), with ABPM only in 24 further participants (33%), and with HBPM only in 2 further participants (3%). Participants who had hypertension according to ABPM but not HBPM were younger (59 ± 11 y versus 67 ± 16 y; p < 0.001) and more frequently still working (83% versus 23%; p < 0.001). The prevalence of WCH was 28%. Among the 32 subjects taking antihypertensive drugs, uncontrolled hypertension was found in 49%. CONCLUSION: This population-based study found a high prevalence of WCH and potential uncontrolled hypertension among individuals with elevated OBPM. This study, therefore, supports the ESH recommendations of complementing OBPM by ABPM or HBPM. The use of HBPM instead of ABPM for the confirmation of hypertension in individuals with elevated OBPM might lead to underdiagnosis and uncontrolled hypertension, in particular in the younger working population. In these individuals, this study suggests using ABPM instead of HBPM.

What is already known?Comparing blood pressure measurements in the doctor's office or clinic (OBPM) with out-of-office measurements (either self-measurement at home (HBPM) or ambulatory over 24 hours during both day and night times (ABPM)) improves the accuracy of hypertension diagnosis.Why was the study done?This study was done to provide additional information by comparing HBPM and ABPM in individuals with elevated OPBMs (≥140/≥90mmHg), who participated in the Swiss Longitudinal Cohort Study (SWICOS)What was found?Our study confirmed differences between office and out-of-office measurements. In 60% of the study participants, ABPM or HBPM confirmed the elevated OBPM but only around half of these participants were treated with antihypertensive drugs. A high proportion of the participants (28%) had white coat hypertension.What does this study add?Our study adds to the literature already available on this issue by reporting on data obtained from a cohort of individuals living in a countryside area of Southern Switzerland.This study also showed that HBPM might underestimate BP in the younger working population.How might this impact on clinical practice?The findings of this population-based study support the European Society of Hypertension recommendations for wider use of out-of-office blood pressure measurement for the confirmation of hypertension in individuals with elevated OBPM to avoid underdiagnosis and uncontrolled hypertension.In the young working population, ABPM should be used instead of only HBPM to confirm hypertension.

The effect of exercise, alcohol or both combined on health and physical performance.

Alcohol (ethanol) is consumed on a daily basis by a large fraction of the population, and in many countries, light-to-moderate alcohol consumption is considered as an integral part of the diet. Although the relationship between alcohol intake and obesity is controversial, regular consumption of alcohol, through its effects in suppressing fat oxidation, is regarded as a risk factor for weight gain, increased abdominal obesity and hypertriglyceridemia. Indeed, alcohol taken with a meal leads to an increase in postprandial lipemia-an effect on postprandial metabolism that is opposite to that observed with exercise. Furthermore, although regular exercise training and/or a preprandial exercise session reduce postprandial lipemia independently of alcohol ingestion, the exercise-induced reduction in postprandial lipemia is nonetheless less pronounced when alcohol is also consumed with the meal. Whether or not alcohol influences exercise and sport performance remains contradictory. It is believed that alcohol has deleterious effects on the performance, although it may contribute to reduce pain and anxiety. The alcohol effects on sports performance depend on the type and dosage of alcohol, acute vs chronic administration, the alcohol elimination rate as well as the type of exercise.

TNF receptors in the microvascular pathology of acute respiratory distress syndrome and cerebral malaria.

The microvascular endothelial cell (MVEC) is a major target of inflammatory cytokines overproduced in conditions such as sepsis and infectious diseases. We addressed the direct and indirect effects of tumor necrosis factor (TNF) on endothelial cells that can be relevant for the pathogenesis of septic shock, with particular attention to the acute respiratory distress syndrome (ARDS) and to cerebral malaria (CM). To identify functional and phenotypical changes occurring in MVEC during sepsis, we isolated these cells from the lungs of patients who died of ARDS. The constitutive expression of ICAM-1 and, to a lesser extent, VCAM-1, CD14, and TNFR2 were significantly increased on MVEC isolated from ARDS patients compared with control MVEC, whereas ELAM-1 and TNFR1 were not increased. We found that lung MVEC from ARDS patients present a procoagulant profile and a higher production capacity of interleukin-6 (IL-6) and IL-8 when compared with those from controls. As in pulmonary MVEC derived from ARDS patients, the only TNFR type found up-regulated in brain microvessels during CM was TNFR2. This increase in TNFR2 expression only occurred in CM-susceptible mice at the onset of the neurological syndrome. We therefore investigated the role of TNFR2 in the development of this brain pathology by comparing the incidence of CM in wild-type and TNF receptor knock-out mice. Unexpectedly, the genetic deficiency in TNFR2, but not in TNFR1, conferred protection against CM and its associated mortality. No ICAM-1 up-regulation was detected in the brain of Tnfr2 knockout mice, indicating a close correlation between protection against CM-associated brain damage, absence of TNFR2, and absence of ICAM-1 up-regulation in the brain. Our results in ARDS and CM indicate a specific up-regulation of TNFR2, but not of TNFR1, on lung and brain MVEC, respectively. This increased expression leads to a reduced sensitivity toward TNFR1-mediated phenomena, such as the sensitized TNF cytolytic activity on lung MVEC. In contrast, the sensitivity toward TNFR2-mediated effects, such as ICAM-1 induction by membrane-bound TNF, is increased on brain and lung MVEC expressing increased levels of TNFR2. Therefore, the ICAM-1-inducing effect, rather than the direct cytotoxicity of inflammatory cytokines, such as TNF, appears to be crucial in ARDS and CM-induced endothelial damage, and TNFR2 seems to play an important role in this activity in vivo.

Carbohydrates and dietary fiber.

The most widely spread eating habit is characterized by a reduced intake of dietary fiber, an increased intake of simple sugars, a high intake of refined grain products, an altered fat composition of the diet, and a dietary pattern characterized by a high glycemic load, an increased body weight and reduced physical activity. In this chapter the effects of this eating pattern on disease risk will be outlined. There are no epidemiological studies showing that the increase of glucose, fructose or sucrose intake is directly and independently associated with an increased risk of atherosclerosis or coronary heart disease (CHD). On the other hand a large number of studies has reported a reduction of fatal and non-fatal CHD events as a function of the intake of complex carbohydrates--respectively 'dietary fiber' or selected fiber-rich food (e.g., whole grain cereals). It seems that eating too much 'fast' carbohydrate [i.e., carbohydrates with a high glycemic index (GI)] may have deleterious long-term consequences. Indeed the last decades have shown that a low fat (and consecutively high carbohydrate) diet alone is not the best strategy to combat modern diseases including atherosclerosis. Quantity and quality issues in carbohydrate nutrient content are as important as they are for fat. Multiple lines of evidence suggest that for cardiovascular disease prevention a high sugar intake should be avoided. There is growing evidence of the high impact of dietary fiber and foods with a low GI on single risk factors (e.g., lipid pattern, diabetes, inflammation, endothelial function etc.) as well as also the development of the endpoints of atherosclerosis especially CHD.

Is it worth treating fever in intensive care unit patients? Preliminary results from a randomized trial of the effect of external cooling.

BACKGROUND: Antipyresis is a common clinical practice in intensive care, although it is unknown if fever is harmful, beneficial, or a negligible adverse effect of infection and inflammation. METHODS: In a randomized study, rectal temperature and discomfort were assessed in 38 surgical intensive care unit patients without neurotrauma or severe hypoxemia and with fever (temperature >/=38.5 degrees C) and systemic inflammatory response syndrome. Eighteen patients received external cooling while 20 received no antipyretic treatment. RESULTS: Temperature and discomfort decreased similarly in both groups after 24 hours. No significant differences in recurrence of fever, incidence of infection, antibiotic therapy, intensive care unit and hospital length of stay, or mortality were noted between the groups. CONCLUSIONS: These results suggest that the systematic suppression of fever may not be useful in patients without severe cranial trauma or significant hypoxemia. Letting fever take its natural course does not seem to harm patients with systemic inflammatory response syndrome or influence the discomfort level and may save costs.

[Fruit and vegetable]. / Früchte und Gemüse.

An increased fruit and vegetable intake is associated with a reduced risk for chronic diseases. The protective effects are due to different mechanisms such as an increased intake of essential micronutrients as well as different non-nutritive phytochemicals. A dietary pattern characterised by a high intake of fruits and vegetables has a much higher protective effect than the intake of pharmacological doses of single nutrients or phytochemicals.

Vitamin requirements of the elderly.

In general, low dietary intakes can account for much of poor vitamin nutriture reported among various elderly populations. Despite problems in assessing vitamin nutriture in the elderly, the 1980 RDAs for thiamin, riboflavin, and ascorbic acid seem appropriate for those populations. However, RDAs for vitamin A and folate may be too high and the RDAs for vitamin D, vitamin B-6, and vitamin B-12 may be too low, due to specified age-related changes in the metabolism of these vitamins. For vitamin E, vitamin K, niacin, biotin, and pantothenic acid, the data is conflicting and/or insufficient to make a judgment about the appropriateness of the RDAs or to estimate safe and adequate daily intakes for the elderly.

Vitamin requirements of elderly people: an update.

This article is an update of our 1987 literature review of vitamin requirements of elderly people (Am J Clin Nutr 1987;45:501-12). Poor dietary intake is the cause of much vitamin malnutrition in elderly people. Nevertheless, there is strong evidence that aging affects the requirement for certain vitamins. The 1989 recommended dietary allowances (RDAs) appear to be too low for elderly people for vitamin D, riboflavin, vitamin B-6, and vitamin B-12, and too high for vitamin A. For several vitamins there is enough information to establish an RDA for the category > or = 70 y.

Ethanol suppresses smooth muscle cell proliferation in the postprandial state: a new antiatherosclerotic mechanism of ethanol?

Epidemiologic studies suggest that moderate amounts of ethanol may reduce cardiovascular risk. The mechanisms of the alcohol-associated risk reduction are not known exactly. Vascular smooth muscle cell proliferation represents an important phenomenon in the pathogenesis of atherosclerosis. Recently, it was suggested that metabolic changes during the postprandial phase may be important in the pathogenesis of atherosclerosis. Therefore, we evaluated the effect of postprandial plasma with and without ethanol on the proliferation of rat vascular smooth muscle cells. Identical meals containing 1 g fat/kg body wt were given with and without ethanol (38 +/- 0.5 g) to eight healthy young men. Blood was drawn hourly during an 8-h postprandial period; the plasma was separated and added to the cell cultures (0.3%, by vol). The proliferative response (DNA synthesis) of these cells was assessed by measuring the incorporation of [methyl-3H]thymidine. The maximal blood ethanol concentration of 11.5 +/- 0.6 mmol/L (mean +/- SEM) was attained within the first hour. The ingestion of the meal with ethanol led to a 20% reduction in the capacity of postprandial plasma to induce thymidine incorporation into smooth muscle cells compared with the meal without ethanol (P < 0.05). These results suggest that ethanol may reduce cardiovascular risk by modulating vascular muscle cell growth during the postprandial period. Considering the amount of time humans spend in the postprandial state during their lifetimes, these findings may be of great importance in the pathogenesis of atherosclerosis.

Mineral requirements of elderly people.

Poor mineral nutrition reported in elderly people is attributed in large part to low dietary intake. Evaluation of the adequacy of mineral nutriture is limited for several minerals because of inadequate methods for assessing mineral status. In addition, there is a general lack of information about mineral nutriture and metabolism in very old people (> 85 y). Given these reservations, the 1989 recommended dietary allowance (RDA) for iron, zinc, and selenium appears adequate for elderly people, as does the estimated safe and adequate daily dietary intake (ESADDI) recommendation for copper. In contrast, the current RDAs for calcium and magnesium and the ESADDI for chromium need careful reevaluation. Current recommendations for calcium may be too low, whereas those for magnesium and chromium may be higher than necessary. For phosphorus, iodine, manganese, fluoride, and molybdenum the available data are insufficient to make a critical judgment about the appropriateness of the dietary recommendations for elderly people.

Relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids.

We evaluated the relation between beta-carotene intake and plasma and adipose tissue concentrations of carotenoids and retinoids. In Study 1, beta-carotene intakes were significantly greater in vegetarians than in nonvegetarians. Plasma concentrations of beta-carotene were also significantly higher in vegetarians than in nonvegetarians but only after two nonvegetarians with excessive intake of carrots were omitted. Plasma retinoid (retinol, retinyl esters, and retinoic acid) concentrations were not different between the two groups. In Study 2, female subjects ingested a daily placebo or 90 mg beta-carotene for 3 wk. In the group fed beta-carotene, plasma beta-carotene concentrations were significantly increased from baseline at 1, 2, and 3 wk. No beta-carotene changes were observed in the placebo-fed group. Plasma retinoid concentrations did not change in either group. In Study 3, adipose tissue beta-carotene and retinoid concentrations were measured in men after an oral beta-carotene dose (120 mg, experimental subjects) or no beta-carotene (control subjects). In the experimental subjects, adipose beta-carotene concentrations increased from baseline at 5 and 10 d postdosing. The control group's adipose tissue beta-carotene concentration did not change over a 10-d period. Changes in retinoids in adipose tissue were not significant in either group. In conclusion, dietary and supplemental beta-carotene increased plasma beta-carotene concentrations but had no effect on plasma retinoid concentrations. There may be little tissue metabolism of beta-carotene to retinoids. Therefore, the anticarcinogenic effect of beta-carotene, if any, may be due to properties of the molecule itself.

Contour-clamped homogeneous electric field gel electrophoresis as a powerful epidemiologic tool in yeast infections.

To examine the longitudinal and cross-sectional patterns of yeast colonization in critically ill patients using genotypic characteristics defined by contour-clamped homogeneous electric field (CHEF) gel electrophoresis, 322 clinical isolates of Candida species were prospectively collected from 29 critically ill patients under routine surveillance over a 6-month period. All isolates, recovered from multiple anatomic sites and from the same sites on different days, were characterized by several identification methods (germ tube test), phenotyping (API system), and genotyping (electrophoretic karyotyping). Electrophoretic karyotype (EK) was determined using pulsed field electrophoresis with the CHEF technique. We used a karyotyping system for Candida albicans (EK code) that facilitated intraspecies delineation. C. albicans colonized 83% of the 29 patients. Candida sp. strains isolated from an individual patient had an identical EK pattern, even when isolated from different body sites, and remained the same over a prolonged period, up to 140 days. EK delineated not only the different Candida species, but also different strains of C. albicans. Strains of C. albicans isolated from different patients were distinguished using the EK pattern, but not API system. Minor variations in EK pattern could be demonstrated in a minority of strains recovered from four patients and were interpreted as chromosomal rearrangements between parent strains. Severe candidal infections, including eight episodes of fungemia, occurred in 11 of 29 patients (38%). All patients had been previously colonized with strains with identical EK patterns. Infection occurred a mean of 25 days after initial surveillance cultures grew yeast. No horizontal transmission could be demonstrated during the study period. In conclusion, EK is a reproducible, stable marker allowing inter-, as well as, intraspecies Candida strain delineation. EK strain delineation is a useful tool in candidal epidemiologic and pathogenic studies. Yeast colonization with the same strain preceded infection in critically ill patients.

Is an increased waist : hip ratio the cause of alcohol-induced hypertension? The AIR94 study.

OBJECTIVE: The mechanisms of alcohol-associated hypertension are not known. We tested the hypothesis that the alcohol-associated increase in blood pressure may be caused in part by an alcohol-induced accumulation of abdominal fat. SUBJECTS AND METHODS: A total of 842 non-smoking men (mean +/- SD age 52 +/- 16 years) attending the air-show AIR94 in Bouchs, Switzerland, volunteered to participate in a cross-sectional study. Four alcohol consumption frequency categories were self-reported, together with weight changes since the age of 20 and during the last 2 years. Blood pressure, body weight, height and the waist : hip ratio were measured. RESULTS: The results showed that 83% of the subjects were alcohol-consumers. Systolic (analysis of variance, P = 0.002) and diastolic (P = 0.009) blood pressure and the waist : hip ratio (P>0.0001) increased with increasing alcohol consumption. The self-judged dietary fat intake increased significantly with increasing alcohol consumption. Weight changes over time were positively associated with alcohol consumption. In a regression model alcohol consumption was the fourth most important contributor to systolic and diastolic blood pressure as well as to an increased abdominal fat mass. CONCLUSION: The alcohol-associated increase in blood pressure may be caused in part by an alcohol-induced accumulation of abdominal fat. Alcohol consumption favours the development of a positive energy balance and thus the abdominal deposition of fat, which is associated with an increased blood pressure. To reduce the risk of a positive energy balance and the abdominal deposition of fat, the intake of alcohol should be minimized and physical activity increased whenever possible.

The decrease in organ donations from 1985 to 1990 caused by increasing medical contraindications and refusals by relatives.

After the progressive improvement in the results of organ transplantation we now face the challenge of shortage in organ supply. The decreasing number of organ retrievals performed in 1990 at our hospital has raised questions concerning loss of potential organ donors and opposition to donation by the next of kin. We investigated these questions and the number of organs available per million inhabitants in the area covered by our university hospital. Our surgical intensive care unit provides about 85% of all organ donations for this area. To this end, all 375 deaths occurring in the surgical ICU during the period between January 1, 1985 and December 31, 1990 were analyzed. Of 138 brain-stem deaths, 43 presented medical contraindications preventing organ harvesting for transplantation. Consent for donation was sought from the families of the 95 remaining potential donors and was refused for 17 patients. Organ retrieval followed all of the 78 agreements to donate, so that no suitable donor was lost. Over the 6 years surveyed, a progressive decrease in organs procured was observed, due to an increase of medical contraindications to organ harvesting for transplantation (P less than 0.001) and a higher rate of refusals to donate organs (P less than 0.002). The rate of kidney retrieval was thereby reduced from 45 to less than 25 per million population per year between 1985 and 1990 for our hospital's catchment area. The reasons cited by the families for denying organ donation suggest that the publicity campaigns aimed at the medical community and the public concerning organ transplant programs should be modified, and that a careful selection of indications for transplantation seems mandatory.

Matrix metalloproteinases correlate with alveolar-capillary permeability alteration in lung ischemia-reperfusion injury.

BACKGROUND: Matrix metalloproteinases (MMPs) are able to degrade the endothelial basal lamina and increase vascular permeability. METHODS: In a porcine model of isolated-reperfused lung, we studied the alveolar-capillary permeability and the zymographic expression of MMP-9 and MMP-2 in the bronchoalveolar lavage fluid of lungs submitted ex vivo to ischemia in three preservation solutions [modified Euro-Collins (EC), low-potassium-dextran, modified-blood]. Twenty-two pigs were randomly divided into three groups according to the preservation solution used. One lung of each pig was rapidly reperfused and analyzed (control lung) although the other lung was reperfused and analyzed after 8 hr of ischemia (ischemic lung). RESULTS: Alveolar-capillary permeability, evaluated by the transferrin leak index, was increased after 8 hr of ischemia compared with controls in the three groups, but was significantly higher in the modified EC group. In the EC group, after 8 hr of ischemia, both proMMP-9 and MMP-9 increased significantly (8.8- and 22-fold, respectively) compared with controls and this increase correlated with the transferrin leak index. Neither proMMP-9 nor MMP-9 increased with the other two preservation solutions. The MMP-2 increase after ischemia was smaller and was also restricted to the EC group. CONCLUSION: MMP expression is enhanced during lung ischemia-reperfusion, especially in the presence of EC and this phenomenon correlates with the alteration of alveolar-capillary permeability.

Haemostatic properties of human pulmonary and cerebral microvascular endothelial cells.

Little is known on the haemostatic profiles of human microvascular endothelial cells (MVEC) from different tissues. In addition it is not known whether MVEC from patients display the same haemostatic pattern as MVEC coming from healthy controls. To address these questions MVEC from human lung and brain were isolated and stimulated with tumour necrosis factor alpha (TNF) and E. coli lipopolysaccharide (LPS) for 24 h. The level and the kinetics of procoagulant activity (PCA) and thrombomodulin (TM) expression were found to be different depending on the tissue of origin and on the agonist used. In particular, the inducible PCA was higher in lung than in brain MVEC, an observation that may be related to the frequency of lung involvement in septic shock. Differences were also observed for tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1) with MVEC supernatants or cell lysates. These variables were then measured in lung MVEC purified from patients with acute respiratory distress syndrome (ARDS) and compared to controls. Cells from ARDS patients constitutively expressed more PCA and PAI-1 than controls. The fibrinolytic potential, expressed as t-PA/PAI-1 ratio, was lower in ARDS than in lung MVEC. It is concluded that MVEC display different haemostatic features depending on the tissue they come from and that lung MVEC from ARDS patients present a procoagulant profile when compared with those from controls.

Biventricular volumes and function in patients with adult respiratory distress syndrome ventilated with PEEP.

The ventricular volume and function changes induced by the addition of 12 cm H2O of positive end-expiratory pressure (PEEP) during mechanical ventilation were studied in 11 patients with the adult respiratory distress syndrome. Cardiac output was measured by thermodilution and ventricular ejection fraction by the multiple gated equilibrated cardiac blood pool scintigraphy. Right and left end-diastolic volumes were then calculated by dividing stroke volume by ejection fraction. The PEEP caused a 14 percent decrease of the cardiac output secondary to a decrease in stroke volume. On the basis of the relationship between stroke volume and ventricular end-diastolic volume, we conclude that reduction in preload was the major component of the decrease in cardiac output. After removal of PEEP, we observed a rebound phenomenon characterized by higher values for stroke volume and cardiac output than before the application of PEEP.

Pneumocephalus. A complication of continuous positive airway pressure after trauma.

We report an uncommon and potentially dangerous complication of continuous positive airway pressure (CPAP) applied during spontaneous respiration. A patient with multiple fractures and recurrernt atelectasis developed pneumocephalus on the seventh day of respiratory therapy with CPAP via a face mask. A fracture of the base of the skull, not recognized despite neurologic and radiologic evaluation at admission, was at the origin of this complication.

High frequency jet ventilation and intermittent positive pressure ventilation. Effect of cerebral blood flow in patients after open heart surgery.

Attenuation of ventilator-synchronous pressure fluctuations of intracranial pressure has been demonstrated during high frequency ventilation in animal and human studies, but the consequences of this effect on cerebral blood flow have not been investigated in man. We compared the effects of high frequency jet ventilation and intermittent positive pressure ventilation on CBF in 24 patients investigated three hours after completion of open-heart surgery. The patients were investigated during three consecutive periods with standard sedation (morphine, pancuronium): a. IPPV; b. HFJV; c. IPPV. Partial pressure of arterial CO2 (PaCO2: 4.5-5.5 kPa) and rectal temperature (35.5 to 37.5 degrees C) were maintained constant during the study. The CBF was measured by intravenous 133Xe washout technique. The following variables were derived from the cerebral clearance of 133Xe: the rapid compartment flow, the initial slope index, ie, a combination of the rapid and the slow compartment flows, and the ratio of fast compartment flow over total CBF (FF). Compared to IPPV, HFJV applied to result in the same mean airway pressure did not produce any change in pulmonary gas exchange, mean systemic arterial pressure, and cardiac index. Similarly, CBF was not significantly altered by HFJV. However, important variations of CBF values were observed in three patients, although the classic main determinants of CBF (PaCO2, cerebral perfusion pressure, Paw, temperature) remained unchanged. Our results suggest that in patients with normal systemic hemodynamics, the effects of HFJV and IPPV on CBF are comparable at identical levels of mean airway pressure.

Effect of tidal volume and positive end-expiratory pressure on compliance during mechanical ventilation.

In 12 patients requiring therapy with mechanical ventilation for acute respiratory failure, total static compliance (Cst) increased from 29 +/- 4 ml/cm H2O at a tidal volume (TV) of 5 ml/kg to 42 +/- 7 ml/cm H2O at a TV of 15 ml/kg. Similarly, Cst increased from 42 +/- 7 ml/cm H2O to 52 +/- 8 ml/cm H2O between 0 and 6 cm H2O of positive end-expiratory pressure (PEEP). At high levels of pulmonary inflation (ie, high PEEP and large TV) compliance decreased. The changes of total respiratory compliance with TV were mainly due to changes in pulmonary compliance. With PEEP, the functional residual capacity increased, and specific compliance did not change. Two mechanisms may be responsible for the changes in compliance. First, varying TV or PEEP will alter the position of tidal ventilation on the pressure-volume curve, resulting in an increase in compliance with increasing TV and PEEP up to a point, where overdistention occurs and compliance decreases. Secondly, the function of the surface-lowering substance may be altered in acute pulmonary parenchymal disease, thus disturbing the regulation of surface tension over the range of pulmonary inflation studied.