Accuracy of feedback-controlled oxygen delivery into a closed anaesthesia circuit for measurement of oxygen consumption.

BACKGROUND: Oxygen consumption (V*O2) is rarely measured during anaesthesia, probably because of technical difficulties. Theoretically, oxygen delivery into a closed anaesthesia circuit (V*O2-PF; PhysioFlex Draeger Medical Company, Germany) should measure V*O2. We aimed to measure V*O2-PF in vitro and in vivo. METHODS: Three sets of experiments were performed. V*O2-PF was assessed with five values of V*O2 (0-300 ml min(-1)) simulated by a calibrated lung model (V*O2-Model) at five values of FIO2 (0.25-0.85). The time taken for V*O2-PF to respond to changes in V*O2-Model gave a measure of dynamic performance. In six healthy anaesthetized dogs we compared V*O2-PF with V*O2 measured by the Fick method (V*O2-Fick) during ventilation with nine values of FIO2 (0.21-1.00). V*O2-PF and V*O2-Fick were also compared in three dogs when V*O2 was changed pharmacologically [102 (SD 14), 121 (17) and 200 (57) ml min(-1)]. In patients during surgery, we measured V*O2-PF and V*O2-Fick simultaneously after induction of anaesthesia (n=21) and during surgery (n=17) (FIO2 0.3-0.5). RESULTS: Compared with V*O2-Model, V*O2-PF values varied from time to time so that averaging over 10 min is recommended. Furthermore, at an FIO2 >0.8, V*O2-PF always overestimated V*O2. With FIO2 <0.8, averaged V*O2-PF corresponded to V*O2-Model and adapted rapidly to changes. Averaged V*O2-PF also corresponded to V*O2-Fick in dogs at FIO2 <0.8. V*O2 measured by the two methods gave similar results when V*O2 was changed pharmacologically. In contrast, V*O2-PF systematically overestimated V*O2-Fick in patients by 52 (SD 40) ml min-1 and this bias increased with smaller arteriovenous differences in oxygen content. CONCLUSION: V*O2-PF measures V*O2 adequately within specific conditions.

Partial liquid ventilation: effects of liquid volume and ventilatory settings on perfluorocarbon evaporation.

During partial liquid ventilation perfluorocarbons are eliminated mainly by evaporation via the airways. The effects of intrapulmonary perfluorocarbon volume, respiratory rate, tidal volume, as well as the level of end-expiratory pressure on perfluorocarbon elimination from isolated lungs, were studied. Nonperfused rabbit lungs underwent partial liquid ventilation (2-15 mL x kg(-1) perfluorocarbon) with variable levels of end-expiratory pressure (0-10 cmH2O), respiratory rates (15-60 breaths x min(-1)) and tidal volumes (3.3-10.0 mL x kg(-1)). Evaporative loss of perfluorocarbon was determined gravimetrically as rate of change in lung weight. At constant respiratory settings, intrapulmonary liquid volume determined evaporative loss in a nonlinear fashion. Mean evaporation at a liquid volume of 5 mL x kg(-1) was 13% lower compared to evaporation at a liquid volume of 15 mL x kg(-1). Any increase in end-expiratory pressure reduced perfluorocarbon evaporation, e.g. by approximately 50% when end-expiratory pressure was increased from 0 to 10 cmH2O. At constant end-expiratory pressure and perfluorocarbon filling evaporation increased in a linear fashion with increasing respiratory rate and tidal volume. In summary, the experiments suggested that evaporative loss of perfluorocarbons during partial liquid ventilation of isolated lungs is increased with increasing intrapulmonary liquid volume, respiratory rate and tidal volume and is reduced in a level-dependent fashion by the application of positive end-expiratory pressure.

[Natriuretic peptides: physiological, pathophysiological and clinical aspects]. / Natriuretische Peptide: Physiologische, pathophysiologische und klinische Aspekte.

A milestone was reached in cardiophysiology when in 1981 DeBold demonstrated that the heart functions as an endocrine gland by injecting an extract of atrial muscle into rats, resulting in an induction of natriuresis and a drop in blood pressure. This observation then led to the discovery of a family of related peptides with slightly different amino acid compositions working in concert to achieve the maintenance of sodium and volume homeostasis. The natriuretic peptide family consists of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), C-type natriuretic peptide (CNP), and Urodilatin (URO) with their tissue-specific distribution including the heart (ANP, BNP), brain (ANP, BNP, CNP), endothelial cells (CNP), and kidney (URO). These peptides were thought to be primarily involved in cardiovascular and renal functions but have now proven to play a role in other physiological systems. In view of their known biological effects, therapeutic efficacy from administration of ANP, BNP or URO might be anticipated, for example in acute renal failure or congestive heart failure. A number of clinical trials suggest that application of these peptides may represent a new pharmacological tool in the treatment or prevention of these diseases, but the clinical benefit still needs to be shown in large controlled studies. In addition to therapeutic options it is possible that plasma concentrations of ANP and BNP could play a role as diagnostic and prognostic markers of cardiac dysfunction.

Partial liquid ventilation reduces fluid filtration of isolated rabbit lungs with acute hydrochloric acid-induced edema.

BACKGROUND: Hydrochloric acid aspiration increases pulmonary microvascular permeability. The authors tested the hypothesis that partial liquid ventilation has a beneficial effect on filtration coefficients in acute acid-induced lung injury. METHODS: Isolated blood-perfused rabbit lungs were assigned randomly to one of four groups. Group 1 (n = 6) served as a control group without edema. In group 2 (n = 6), group 3 (n = 6), and group 4 (n = 6), pulmonary edema was induced by intratracheal instillation of hydrochloric acid (0.1 N, 2 ml/kg body weight). Filtration coefficients were determined 30 min after this injury (by measuring loss of perfusate after increase of left atrial pressure). Group 2 lungs were gas ventilated, and group 3 lungs received partial liquid ventilation (15 ml perfluorocarbon/kg body weight). In group 4 lungs, the authors studied the immediate effects of bronchial perfluorocarbon instillation on ongoing filtration. RESULTS: Intratracheal instillation of hydrochloric acid markedly increased filtration coefficients when compared with non-injured control lungs (2.3 +/- 0.7 vs. 0.31 +/- 0.08 ml.min(-1). mmHg(-1).100 g(-1) wet lung weight, P < 0.01). Partial liquid ventilation reduced filtration coefficients of the injured lungs (to 0.9 +/- 0.3 ml.min(-1).mmHg(-1).100 g(-1) wet lung weight, P = 0.022). Neither pulmonary artery nor capillary pressures (determined by simultaneous occlusion of inflow and outflow of the pulmonary circulation) were changed by hydrochloric acid instillation or by partial liquid ventilation. During ongoing filtration, bronchial perfluorocarbon instillation (5 ml/kg body weight) immediately reduced the amount of filtered fluid by approximately 50% (P = 0.027). CONCLUSIONS: In the acute phase after acid injury, partial liquid ventilation reduced pathologic fluid filtration. This effect started immediately after bronchial perfluorocarbon instillation and was not associated with changes in mean pulmonary artery, capillary, or airway pressures. The authors suggest that in the early phase of acid injury, reduction of fluid filtration contributes to the beneficial effects of partial liquid ventilation on gas exchange and lung mechanics.

[Treatment of acute renal failure--concepts and controversies. 2. Extracorporeal renal replacement and peritoneal dialysis]. / Therapie des akuten Nierenversagens--Konzepte und Kontroversen. Teil II--Extrakorporale Nierenersatzverfahren und Peritonealdialyse.

Therapy of prolonged acute renal failure regularly requires a renal replacement therapy. This can be achieved by different extracorporal renal replacement therapies (ERRT) or by peritoneal dialysis. ERRT are classified according to the physical principle underlying toxin elimination as hemodialysis (diffusion) and hemofiltration (convection). Another classification refers to intermittent or continuous application modes. Biocompatibility of membranes is judged according to their activation of the complement system. Prospective randomized studies did not consolidate the assumptions about the benefit of particular modalities proposed on theoretical foundations. Mortality, duration and complication rates of acute renal failure are not significantly decreased by use of biocompatible membranes. Continuous modalities are not generally preferable but optimize treatment in hemodynamically unstable patients, in whom they endorse fluid balancing and maintenance of sufficient arterial blood pressure. The use of demanding hemofiltration techniques for cytokine removal should be limited to clinical studies. The effects of ERRT-"intensity" and the best timing for initiation of ERRT have not been evaluated sufficiently. The choice of the ERRT modality is subject to clinical judgement (criterion: hemodynamic situation), practical aspects (criteria: availability of equipment and handling experience), and costs. Prior to their general use new and expensive technical modalities and membrane types should be thoroughly evaluated in studies with regard to outcome-related aspects such as patient survival and preservation of renal function.

[Treatment for acute renal failure--concepts and controversies. 1. Pharmacologic treatment and experimental strategies]. / Therapie des akuten Nierenversagens--Konzepte und Kontroversen. Teil I--Pharmakologische Behandlung und experimentelle Therapieansätze.

Acute renal failure is the common result of various damaging mechanisms. Prophylaxis and differentiated therapy of acute renal failure are of outmost importance in anaesthesiology and intensive care medicine. The efficiency of pharmacotherapy is narrowly limited. Diuretics increase the urine output, but they do neither ameliorate the clinical course of the patient nor the prognosis of established acute renal failure. Dopamine and natriuretic peptides have no use in prevention and treatment of acute renal failure. Calcium-channel-blockers are valuable in cadaveric kidney transplantation. Osmodiuretics prevent intratubular precipitation of hemoglobin and myoglobin crystals; they also have some value in cadaveric kidney transplantation. Experimental studies investigated the possibility to enhance the regeneration of the tubular epithelial cell. Whereas in vitro studies and studies in animal models using various growth factors yielded promising results, these could not be reproduced in patients with acute renal failure. The physiology of NO in the kidney is incompletely understood. Actual progress is made in the understanding of lipid peroxidation and potential pharmacological implications. The mainstay for the assurance of high-quality patient care remain a vigilant identification of the patient at risk and an arduous search to avoid nephrotoxic substances and situations implicating potential renal damage.

[Antagonist-induced opiate detoxification. Report on clinical experience as well as on short and intermediate range course]. / Antagonisteninduzierte Opiatentgiftung. Erfahrungsbericht zur klinischen Anwendung sowie zum kurz- und mittelfristigen Verlauf.

In a special inpatient unit for detoxification treatment of illicit drugs, antagonist-induced opiate detoxification was studied in five nonselected inpatients with polytoxicomanic abuse. The purpose was to evaluate the feasibility of this detoxification method and its impact on further reaction to treatment. During rapid detoxification under general anesthesia in an intensive care unit, no complications occurred. Withdrawal symptoms were observed in all patients over several days. During the inpatient period, no patient could be motivated to take part in a longer rehabilitation therapy. Most patients were discharged prematurely on their own demand and none made use of the rehabilitation program offered to them. All patients relapsed after relatively short times and three out of five presented for a new detoxification treatment.

Effects of partial liquid ventilation on regional pulmonary blood flow distribution of isolated rabbit lungs.

OBJECTIVE: Partial liquid ventilation with perfluorocarbons may increase alveolar hydrostatic transmural pressure and may result in a redistribution of pulmonary blood flow from dependent to nondependent lung regions. To test this hypothesis under controlled study conditions, we determined intrapulmonary blood flow distributions during gas and perfluorocarbon ventilation in isolated rabbit lungs. DESIGN: Controlled animal study with an ex vivo isolated lung preparation. SETTING: Research laboratory for Experimental Anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: New Zealand White rabbits. INTERVENTIONS: The lungs were perfused with autologous blood at constant flow (150 mL/min) and ventilated with 5% C(O2) in air (positive end-expiratory pressure, 2 cm H2O; tidal volume, 10 mL/kg body weight; respiratory rate, 30 breaths/ min) without and with perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Regional lung perfusion was measured with colored microspheres in apical, central, peripheral, and basal samples before and after bronchial instillation of perfluorocarbons. Compared with gas ventilation, intrapulmonary blood flow during perfluorocarbon ventilation was higher in apical samples (49.4+/-8.6 mL/min/g vs. 38.3+/-6.8 mL/min/g dry weight; p = .03) and lower in basal samples (22.2+/-5.1 mL/min/g vs. 39.9+/-8.2 mL/min/g; p = .04). CONCLUSIONS: Our findings suggest that during partial liquid ventilation, intrapulmonary blood flow is redistributed toward less-dependent lung regions. (Crit Care Med 2000; 28:1522-1525)

Effects of ventilation and nonventilation on pulmonary venous blood gases and markers of lung hypoxia in humans undergoing total cardiopulmonary bypass.

OBJECTIVE: To assess the effects of lung oxygenation and ventilation vs. lung collapse on pulmonary markers of lung hypoxia. DESIGN: A prospective, nonrandomized, nonblinded comparative study. SETTING: University department of anesthesiology and cardiothoracic surgery. SUBJECTS: Twelve adult patients undergoing coronary bypass grafting requiring total cardiopulmonary bypass. INTERVENTIONS: Single lung ventilation during total cardiopulmonary bypass (tidal volume, 150 mL; respiratory rate, 6 breaths/min; inspiratory oxygen fraction, 0.5) while the contralateral lung was allowed to collapse completely without oxygenation. MEASUREMENTS AND MAIN RESULTS: At the beginning and at the end of total cardiopulmonary bypass (duration, 59-65 mins), blood was aspirated from the right and left pulmonary veins and the radial artery for measurement of blood gases and concentrations of endothelin-1, big-endothelin, thromboxane B2, lactate, and lactate dehydrogenase. Nonventilation during total cardiopulmonary bypass compared with ventilation resulted in lower pulmonary venous P(O2) values (57+/-15 torr [7.6+/-2.0 kPa] vs. 103+/-23 torr [13.7+/-3.1 kPa]) and higher thromboxane B2 concentrations (488+/-95 pg/mL vs. 434+/-92 pg/mL). The concentrations of endothelin-1, big-endothelin, lactate, and lactate dehydrogenase in the pulmonary veins did not differ significantly between nonventilated and ventilated lungs. CONCLUSIONS: Development of pulmonary tissue hypoxia during 1 hr of nonventilation and cardiopulmonary bypass with completely inhibited pulmonary arterial blood flow is unlikely, suggesting that enough oxygen is stored in or is provided to the collapsed lung. Thus, nonventilation during total cardiopulmonary bypass does not appear to contribute to postoperative respiratory dysfunction by causing pulmonary tissue hypoxia. These results, however, do not exclude that mechanical factors of ventilation might benefit the lung during cardiopulmonary bypass.

[Heparin induced thrombocytopenia]. / Heparin-induzierte Thrombozytopenie.

Thrombocytopenia is a known adverse reaction occurring in some of the patients receiving heparin. Two types of heparin-induced thrombocytopenia (HIT) have been described. HIT type I is mild thrombocytopenia probably caused by a direct proaggregating effect of heparin and occurs during the first few days of heparin treatment. No specific treatment is necessary. HIT type II is a severe thrombocytopenia mediated by an immunologic mechanism where antibodies against heparin/platelet factor 4 (PF4) complexes play a major role. Thrombocytopenia usually commences 4-14 days after the onset of heparin administration. The incidence of HIT type II is below 3% and even lower when low-molecular weight heparin is used. The possible occurrence of life-threatening thrombembolic events may complicate the course of HIT type II. Diagnosis of HIT type II by clinical features alone is often difficult. A few laboratory tests are pertinent for diagnosing HIT type II including the 14C-serotonin assay, the heparin-induced platelet activation test and the heparin/PF4 ELISA. Immediate cessation of heparin administration is essential in the treatment of patients with HIT type II, if need be even without waiting for the result of the antibody search test. Several alternatives of anticoagulation for patients with HIT type II have been investigated in the past. Danaparoid-sodium as well as recombinant hirudin have shown promising results when used for this purpose.

Effects of partial liquid ventilation with perfluorocarbons on pressure-flow relationships, vascular compliance, and filtration coefficients of isolated blood-perfused rabbit lungs.

OBJECTIVES: The density of perfluorocarbons is almost twice that of blood. Therefore, we hypothesized that partial liquid ventilation with these fluids markedly affects pulmonary hemodynamics and filtration coefficients. To test these hypotheses we studied pressure-flow relationships, vascular compliances, capillary pressures, and filtration coefficients in normal and perfluorocarbon-ventilated rabbit lungs. DESIGN: Controlled animal study with an ex-vivo isolated lung preparation. SETTING: Research laboratory for experimental anesthesiology at the Heinrich-Heine-University of Düsseldorf. SUBJECTS: Fourteen New Zealand White rabbits. INTERVENTIONS: The lungs were perfused under zone 3 flow conditions with autologous blood at various flow rates (50 to 250 mL/min, closed circuit, roller pump, 37 degrees C) and ventilated with 5% CO2 in air (positive end-expiratory pressure: 2 cm H2O, tidal volume: 10 mL/kg, respiratory rate: 30 breaths/min) without (control group, n=7) and with (n=7) perfluorocarbon administered intratracheally (15 mL/kg). MEASUREMENTS AND MAIN RESULTS: Pulmonary arterial, left atrial, and airway pressures, as well as blood reservoir volume (reflecting changes in pulmonary blood volume) and lung weight, were measured continuously. Inconsistent with our hypothesis, we found no significant differences between both groups in the slopes and intercepts of the pressure-flow relationships. There were no significant differences in capillary pressures determined by double occlusion (6.7+/-1.2 vs. 6.3+/-1.3 cm H2O for control group, p=.53), vascular compliances (0.51+/-0.10 vs. 0.47+/-0.09 mL/cm H2O for control group, p=.38), and filtration coefficients (0.33+/-0.06 vs. 0.37+/-0.07 mL/min/mm Hg/100 g wet weight for control group, p=.80, Mann-Whitney). CONCLUSIONS: Partial liquid ventilation with perfluorocarbons has no relevant effects on pulmonary filtration coefficients and global hemodynamic variables of isolated zone 3 lungs. These findings suggest that right ventricular afterload is not changed with partial liquid ventilation. It is likely, however, that intrapulmonary blood flow is redistributed toward less-dependent regions, although relevant global hemodynamic changes are absent during partial liquid ventilation.

[Low dosage dopamine improves kidney function: current status of knowledge and evaluation of a controversial topic]. / Niedrig dosiertes Dopamin verbessert die Nierenfunktion: Derzeitiger Kenntnisstand und Bewertung einer kontroversen Diskussion.

The ability of low dose dopamine (1-3 micrograms x kg-1 x min-1) to cause selective renal vasodilation, to increase glomerular filtration rate, urine output, and natriuresis, is intuitively considered favourable. Dopamine, therefore, continues to be used in critically ill patients to preserve or improve renal function. Despite its application in a wide variety of disease states and in patients at risk of acute renal failure or with already decreased renal function, there is no conclusive evidence that "renal doses" of dopamine prevented acute renal failure or had any positive effect on patient outcome although it increased urine output and natriuresis consistently. Data from many clinical studies, however, are difficult to interpret due to small numbers of patients, the absence of control groups, the inability to exclude changes in cardiac output or to separate a diuretic effect of dopamine in the tubulus system from specific increases of glomerular filtration rate, and because of the variability of methods to determine renal performance (i.e. creatinine clearance, urine output, natriuresis, fractional excretion of sodium). Moreover, the routine use of dopamine is not innovous, since it may worsen gut ischaemia and suppress certain hormonal systems. Those who believe in the clinical benefits of "renal dose" dopamine argue that, even in the absence of an improvement in renal function, the maintenance of urine output could be useful in patients unresponsive to diuretics. Again, the clinical benefit of this diuretic action still needs to be shown. In conclusion, there is little justification for the routine administration of low-dose dopamine in patients at risk of renal failure. Large controlled clinical studies are urgently needed to determine whether dopamine improves renal function or prevents acute renal failure in patients at risk.

How much oxygen does the human lung consume?

BACKGROUND: The amount of oxygen consumed by the lung itself is difficult to measure because it is included in whole-body gas exchange. It may be increased markedly under pathological conditions such as lung infection or adult respiratory distress syndrome. To estimate normal oxygen consumption of the human lung as a basis for further studies, respiratory gas analysis during total cardiopulmonary bypass may be a simple approach because the pulmonary circulation is separated from systemic blood flow during this period. METHODS: Lung oxygen consumption was determined in 16 patients undergoing cardiac surgery. During total cardiopulmonary bypass their lungs were ventilated with low minute volumes (tidal volume, 150 ml; rate, 6 min-1; inspiratory oxygen fraction, 0.5; positive end-expiratory pressure, 3 mmHg). All expiratory gas was collected and analyzed by indirect calorimetry. As a reference value also, whole-body oxygen consumption of these patients was determined before total cardiopulmonary bypass. In a pilot study of eight additional patients (same ventilatory pattern), the contribution of systemic (bronchial) blood flow to pulmonary gas exchange during cardiopulmonary bypass was assessed. For this purpose, the amount of enflurance diffusing from the systemic blood into the bronchial system was measured. RESULTS: The human lung consumes about 5-6 ml oxygen per minute at an esophageal temperature of 28 degrees C. Prebypass whole-body oxygen consumption measured at nearly normothermic conditions was 198 +/- 28 ml/min. Mean lung and whole-body respiratory quotients were similar (0.84 and 0.77, respectively). Extrapolating lung oxygen consumption to 36 degrees C suggests that the lung consumes about 11 ml/min or about 5% of total body oxygen consumption. Because the amount of enflurane diffused from the systemic circulation into the bronchial system during cardiopulmonary bypass was less than 0.1%, the contribution of bronchial blood flow to lung gas exchange can be assumed to be negligible. CONCLUSIONS: The lung consumes about 5% of whole-body oxygen uptake.

Small, oral dose of clonidine reduces the incidence of intraoperative myocardial ischemia in patients having vascular surgery.

BACKGROUND: Most new perioperative myocardial ischemic episodes occur in the absence of hypertension or tachycardia. The ability of alpha 2-adrenoceptor agonists to inhibit central sympathetic outflow may benefit patients with coronary artery disease by increasing the myocardial oxygen supply and -demand ratio. METHODS: A randomized double-blind study design was used in 297 patients scheduled to have elective vascular surgical procedures to evaluate the effects of 2 micrograms/kg-1 oral clonidine (n = 145) or placebo (n = 152) on the incidence of perioperative myocardial ischemic episodes, myocardial infarction, and cardiac death. Continuous real-time S-T segment trend analysis (lead II and V5) was performed during anesthesia and surgery and correlated with arterial blood pressure and heart rate before and during ischemic events. Dose requirements for vasoactive and antiischemic drugs to control blood pressure and heart rate as well as episodes of myocardial ischemia (i.e., catecholamines, beta-adrenoceptor antagonists, nitrates, and systemic vasodilators) and fluid volume load were recorded. RESULTS: Administration of clonidine reduced the incidence of perioperative myocardial ischemic episodes from 39% (59 of 152) to 24% (35 of 145) (P < 0.01). Hemodynamic patterns, percentage of ischemic time, and the number of ischemic episodes per patient did not differ. Nonfatal myocardial infarction developed after operation in four patients receiving placebo compared with none receiving clonidine (day 2 to 21; P = 0.07). The incidence of fatal cardiac events (1 vs. 2) was not different. Dose requirements for vasoactive and antiischemic drugs did not differ between the groups, but the amount of presurgical fluid volume was slightly greater in patients receiving clonidine (951 +/- 388 vs. 867 +/- 381 ml; P < 0.03). CONCLUSION: A small oral dose of clonidine, given prophylactically, can reduce the incidence of perioperative myocardial ischemic episodes without affecting hemodynamic stability in patients with suspected or documented coronary artery disease.

Is inhibition of oxygen radical production of neutrophils by sympathomimetics mediated via beta-2 adrenoceptors?

Despite their beneficial effects on cardiovascular derangements in patients with severe sepsis, high doses of sympathomimetics might contribute to an impaired neutrophil function. This study was conducted to examine whether various sympathomimetics [(-)-epinephrine (EPI), dopamine (DA) and dobutamine (DOB)] differ in their potency to suppress the formation of oxygen radicals by neutrophils and whether this potency correlates with their affinity to or intrinsic activity for beta-2 adrenoceptors (beta-2 AR). Oxygen radical production of human neutrophils was induced by N-formyl-methionyl-leucyl-phenyl-alanine and detected by chemiluminescence measurements. Dose-response curves for the inhibition of chemiluminescence by sympathomimetics were measured in the absence and presence of 0.1 microM CGP 20,712 A (1-[2(3-carbamoyl-4-hydroxy phenoxy)-ethylamino]-3-[4-(1-methyl-4-trifluoromethyl-2-imidazolyl) phenoxy]-2-propanol methanesulfonate) and 0.1 microM ICI 118,551 (erythro-(+/-)-1-(7-methylindan-4-yloxy)-3 isopropylaminobutan-2-ol hydrochloride) to selectively antagonize beta-1 AR and beta-2 AR, respectively. Inhibition of chemiluminescence of neutrophils by EPI was approximately 100-fold more potent than that by DA and DOB. Only the inhibition curve by EPI exhibited two components, one at nanomolar and one at micromolar concentrations. The nanomolar component was sensitive against beta-2 AR blockade, whereas the micromolar one was insensitive against both beta AR antagonists. Dose-response curves for DA and DOB exhibited a simple hyperbolic shape at micromolar concentrations and were insensitive against both beta AR antagonists. Maximum inhibition by DA and DOB was equipotent to that by EPI. However, the EC50 for DA was much lower than its dissociation constants, KD, assayed in membrane preparations by radioligand binding, whereas the EC50 of DOB matched KD. This difference could not be explained by a different efficiency of signal transduction, which was determined in receptor-coupled adenylate cyclase activity and which only showed a slightly higher efficiency of DA (51%) than of DOB (34%). Therefore, sympathomimetics were also investigated in a cell-free system, in which chemiluminescence was generated by horseradish peroxidase with hydrogen peroxide as substrate. Surprisingly, all of the sympathomimetics suppressed chemiluminescence with micromolar concentrations. We conclude that sympathomimetics with high affinity and high intrinsic activity (EPI) inhibit neutrophil function via occupation of beta-2 AR, whereas sympathomimetics with low affinity (DA) or low intrinsic activity (DOB) may act by direct scavenging of oxygen radicals.