Validation of cardiac output monitoring based on uncalibrated pulse contour analysis vs transpulmonary thermodilution during off-pump coronary artery bypass grafting.

BACKGROUND: Cardiac output monitoring, as a part of a goal-directed haemodynamic management, has been shown to improve perioperative outcome in high-risk patients undergoing major surgical interventions. However, thorough validation of cardiac output monitoring devices in different clinical conditions is warranted. The aim of our study was to compare the reliability of a novel system for cardiac index (CI) monitoring based on uncalibrated pulse contour analysis (UPCA) with transpulmonary thermodilution (TPTD) during off-pump coronary artery bypass grafting (OPCAB). METHODS: Twenty patients undergoing elective OPCAB were enrolled into the study. CI measured by means of UPCA (CIUPCA) was validated against CI determined with TPTD technique (CITPTD). Parallel measurements of CI were performed at nine stages during the surgery and after operation. We assessed the accuracy and the precision of individual values and the agreement of trends of changes in CI. RESULTS: Totally, 180 pairs of data were collected. There was a significant correlation between CIUPCA and CITPTD (ρ=0.836, P<0.01). According to a Bland-Altman analysis, the mean bias between the methods was -0.14 litre min(-1) m(-2) with limits of agreement of ±0.82 litre min(-1) m(-2) and a percentage error of 31%. A polar plot trend analysis revealed acceptable angular bias (-0.54°), increased radial limits of agreement (±52.7°), and decreased polar concordance rate (74%). CONCLUSIONS: In OPCAB, UPCA provides accurate and precise CI measurements compared with TPTD. However, the ability of this method to follow trends in cardiac output is poor. CLINICAL TRIAL REGISTRATION: NCT01773720 (ClinicalTrials.gov).

The effects of methylene blue on ovine post-pneumonectomy pulmonary oedema.

BACKGROUND: We recently reported that post-pneumonectomy pulmonary oedema (PPO) occurs after ventilating the remaining lung with excessive tidal volumes. Studies in small animals have indicated that nitric oxide (NO) release increases in hyper-inflated lungs, but confirmatory evidence from larger animals is still lacking. We hypothesized that PPO could be prevented by methylene blue (MB), an inhibitor of NO synthase. METHODS: Sheep were subjected to a right-sided pneumonectomy (PE) and randomly assigned to a protectively ventilated group ((PROTV group, n=7) with tidal volumes of 6 ml/kg at 20 inflations/min and a positive end-expiratory pressure (PEEP) of 2 cmH(2)O, and two groups undergoing 'injurious ventilation' (INJV) with tidal volumes of 12 ml/kg and zero end-expiratory pressure (ZEEP), a control group (INJV group, n=7) and a treatment group subjected to MB 1 h after PE (INJV+MB group, n=7). Haemodynamic variables, lung mechanics, blood gases and plasma nitrites and nitrates (NOx) were determined. RESULTS: PE reduced pulmonary blood volume, extravascular lung water (EVLWI) and quasistatic lung compliance in all groups, in parallel with a rise in peak airway pressure (P<0.05). In the INJV group, pulmonary arterial pressure, EVLWI and pulmonary vascular permeability index increased and arterial oxygenation decreased towards cessation of the experiments. These changes were not antagonized by MB. Plasma NOx increased in all the groups compared with baseline, but with no intergroup difference. CONCLUSION: MB did not reduce PPO and accumulation of NOx in sheep subjected to ventilation with excessive tidal volumes and ZEEP.

Radiographic lung density assessed by computed tomography is associated with extravascular lung water content.

BACKGROUND: We hypothesized that in acute lung injury (ALI), the volume of pulmonary tissue with aqueous density, as determined by spiral computed tomography (CT), is associated with extravascular lung water content. Our aim was to compare tissue volume index, as assessed by CT, before and after oleic acid-induced ALI, with extravascular lung water indexes (EVLWI), determined with single transpulmonary thermodilution (EVLWI(STD)), thermal-dye dilution (EVLWI(TDD)), and postmortem gravimetry (EVLWI(G)). METHODS: Seven instrumented sheep received an intravenous infusion of oleic acid 0.08 ml/kg (OA group) and four animals had vehicle only (Control group). The day before, and immediately after the experiment, sheep were anesthetized to undergo quantitative CT examinations during a short breath hold. Hemodynamics, oxygenation, EVLWI(STD), and EVLW(TDD) were registered. Linear regression analysis was used to assess the relationships between EVLWI(STD), EVLW(TDD), EVLWI(G), and lung tissue volume index (TVI(CT)) determined with CT. RESULTS: In the OA group, total lung volume increased compared with Controls. Poorly and non-aerated lung volumes increased a 3.6- and 4.9-fold, respectively, and TVI(CT) almost doubled. EVLWI(STD), EVLWI(TDD), and TVI(CT) were associated significantly with EVLWI(G) (r=0.85, 0.90, and 0.88, respectively; P<0.001). TVI(CT) deviated from the reference EVLWI(G) values to the greatest extent with a mean bias +/- 2SD of 4.0 +/- 6.0 ml/kg. CONCLUSIONS: In ovine oleic acid-induced ALI, lung tissue volume, as assessed by quantitative CT, is in close agreement with EVLWI, as determined by indicator dilution methods and postmortem gravimetry, but overestimates lung fluid content.

Single transpulmonary thermodilution and continuous monitoring of central venous oxygen saturation during off-pump coronary surgery.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) requires thorough monitoring of hemodynamics and oxygen transport. Our aim was to find out whether therapeutic guidance during and after OPCAB, using an algorithm based on advanced monitoring, influences perioperative hemodynamic and fluid management as well as the length of post-operative ICU and hospital stay. METHODS: Patients were randomized into two groups of hemodynamic monitoring: the conventional monitoring (CM) group (n=20) and the advanced monitoring (AM) group (n=20). In the CM group, therapy was guided by central venous pressure, mean arterial pressure (MAP) and heart rate (HR), and in the AM group by the intrathoracic blood volume index, MAP, HR, central venous oxygen saturation (ScvO(2)) and cardiac index (CI). The measurements were performed before and during surgery, and at 2, 4 and 6 h post-operatively. RESULTS: In the AM group, colloids and dobutamine were given more frequently and were accompanied by increments in ScvO(2), CI and oxygen delivery compared with baseline. The percentage of ephedrine administration was higher in the CM group. The algorithm guided by AM decreased time until achieving the status of 'fit for ICU discharge' and post-operative hospital stay by 15% and 25%, respectively. CONCLUSIONS: A goal-directed algorithm based on advanced hemodynamic monitoring and continuous measurement of ScvO(2) facilitates early detection and correction of hemodynamic changes and influences the strategy for fluid therapy that can improve the course of post-operative period after coronary artery bypass grafting on the beating heart.

[Assessment of current methods quantitating extravascular lung water and pulmonary aeration in inhomogeneous lung injury: an experimental study].

BACKGROUND: Single transpulmonary thermodilution (STTD) is a widely recognized technique for the quantification of extravascular lung water (EVLW). However, the accuracy of STTD can be substantially reduced in acute lung lesion (ALL) characterized by inhomogeneous distribution of edematous zones and major ventilation-perfusion mismatch. Quantitative computed tomography (CT) may be a helpful clinical adjunct allowing an assessment of pulmonary gas and tissue content. The purpose of the study was to compare the tissue volume index, as estimated by spiral CT (TVICT), with EVLW indices determined with STTD (EVLWISTTD), thermal-dye dilution (EVLWITDD), and postmortem gravimetry (EVLWIG) before and after oleic acid-induced ALL in sheep. MATERIALS: Eleven yearling sheep were randomly assigned to either an oleic acid (OA) group receiving an infusion of OA in a dose of 0.08 ml/kg i.v. or to a control group. The day before and immediately after the experiment, sheep underwent CT examinations. Pulmonary and systemic hemodynamics, oxygenation, EVLWISTTD and EVLWITDD were recorded. Linear regression analysis was used to assess the relationships between EVLWISTTD, EVLWITDD, EVLWIG, and TVICT (syngo PulmpCT, Siemens, Germany). RESULTS: OA caused 5- and 7-fold increments in poorly and nonaerated lung volumes, respectively, and increased total lung volume and TVICT, EVLWISTTD, EVLWITDD, and TVICT demonstrated a close agreement with EVLWIG (r = 0.86, 0.90, and 0.97, respectively; p < 0.001). TVICT overestimated reference EVLWIG values to the greatest extent. CONCLUSION: In a sheep model of OA-induced ALL, pulmonary tissue volume as estimated by quantitative CT closely correlates with EVLWI measured by dilutional methods and postmortem gravimetry.

Methylprednisolone attenuates airway and vascular responses induced by reactive oxygen species in isolated, plasma-perfused rat lungs.

The effects of methylprednisolone (MP) on the acute airway and pulmonary vascular responses induced by reactive oxygen species (ROS) were investigated in isolated, plasma-perfused rat lungs. ROS were generated by adding xanthine oxidase and hypoxanthine to the perfusate. MP was administered in 3 different ways: 1. Added to the perfusate (1 mg*ml-1) 5 min prior to xanthine oxidase and hypoxanthine, 2. Given as intraperitoneal injections (40 mg*kg-1) to lung donor rats 12 and 2 hours prior to the experiments, or 3. Combining 1 and 2. The lungs were perfused at constant volume inflow (15 ml*min-1). Pulmonary arterial pressure and transpulmonary pressure were followed for 30 min after addition of xanthine oxidase and hypoxanthine. ROS induced a powerful, acute broncho- and vasoconstriction, which was inhibited by addition of MP to the perfusate. Pretreatment with MP also inhibited the vascular and airway responses. Adding MP to the perfusate of pretreated lungs further reduced the ROS-induced smooth muscle constriction. In conclusion, MP inhibits vasoconstriction and bronchoconstriction induced by ROS in isolated rat lungs.

[Monitoring of extravascular lung water in patients with severe sepsis]. / Monitoring vnesosudistoi vody legkikh u bol'nykh s tiazhelym sepsisom.

The key objective of the case study was the possibility to monitor the extravascular lung water (EVLW) in severe cases. Twelve mechanically ventilated patients with severe sepsis complicated by septic shock and by an acute lung injury (ALI) were involved in the prospective study. The measurements, performed on days 1 and 3 after the onset of sepsis, comprised hemodynamics, EVLW as assessed by Pulsion PiCCO method, blood gases and severity scores. The EVLW correlated significantly with lung injury score (r = 0.46), oxygenation (r = -0.46) and with pulmonary compliance (r = -0.58) versus the central venous pressure. The EVLW and lung injury scores were found to be essentially higher in non-survivors on day 3. The clinical situations, described in the present article, are indicative of a potential EVLW value applicable to sepsis treatment. Finally, the monitoring of EVLW is a useful tool in the purpose-oriented therapy of sepsis-induced ALI; moreover, the method has an important prognostic value.

Single transpulmonary thermodilution in off-pump coronary artery bypass grafting: haemodynamic changes and effects of different anaesthetic techniques.

BACKGROUND: Off-pump coronary artery bypass grafting (OPCAB) can be associated with severe cardiovascular changes, thus requiring advanced haemodynamic monitoring. Our aim was to investigate the feasibility of transpulmonary single thermodilution (STD) combined with pulse-contour analysis, a newly introduced method for cardiovascular monitoring, for assessment of changes in haemodynamics during different anaesthetic techniques in OPCAB. METHODS: Thirty-six patients scheduled for elective OPCAB were randomized to receive anaesthesia either with midazolam, propofol or isoflurane, in addition to fentanyl and pipecuronium. After catheterization of the femoral artery, haemodynamic parameters were assessed using STD and pulse-contour analysis. The measurements were performed after induction of anaesthesia, during surgery and at 2, 4 and 6 h post-operatively. RESULTS: At the end of surgery, the global ejection fraction decreased by 29% and 19% in the midazolam and the propofol groups, respectively, (P < 0.05) but remained unchanged in the isoflurane group. Moreover, in the isoflurane group, the left ventricular contractility index was higher and the mean arterial pressure (MAP) and the systemic vascular resistance index (SVRI) decreased in comparison with pre-operative values. Post-operatively, the cardiac index (CI) and the cardiac function index (CFI) increased in all groups (P < 0.05). The peri-operative requirement for ephedrine and nitroglycerin increased in the propofol and the midazolam groups, respectively (P < 0.05). CONCLUSION: During OPCAB, STD and pulse-contour analysis displayed changes in preload, myocardial function and afterload that gave valuable guidance for the conduct of anaesthesia, fluid management, and the administration of vasoactive agents. As assessed using STD, isoflurane within the present dose range appears to maintain myocardial performance and vascular tone better than midazolam or propofol.

Hypoxia-induced vasoconstriction in isolated perfused lungs exposed to injectable or inhalation anesthetics.

Investigations during the last two decades have revealed a tendency to inpaired pulmonary gas exchange in patients during general anesthesia. In the awake state, arterial hypoxemia is counteracted by a mechanism which tends to normalize the ventilation/perfusion ratio of the lungs by way of a hypoxia-induced vasoconstriction in poorly ventilated areas. This results in a redistribution of perfusion to more adequately ventilated lung regions. Recent observations suggest, however, that this beneficial mechanism is blunted by some commonly used inhalation anesthetics. In the present study the effect of inhalation anesthetics and injectable anesthetics on the vasoconstrictor response to acute alveolar hypoxia have been compared in isolated blood-perfused rat lungs. The experiments showed that the response was unaffected by N2O and injectable anesthetics, while a reversible, dose-dependent damping effect was demonstrated for the volatile inhalation anesthetics, ether, halothane and methoxyflurance. The effect could be demonstrated at blood concentrations comparable to those used in clinical anesthesia, and it was not due to a general paralysis of the vascular smooth muscle. The findings might, at least in part, explain the occurrence of arterial hypoxemia during general inhalation anesthesia.

Constant flow- vs. constant pressure-perfusion for studies of pulmonary vasoactive responses.

We have compared the pulmonary vascular responses to a standardized hypoxic vasoconstrictor stimulus (FIO2 = 0.02) obtained during 1) constant volume inflow, with pulmonary arterial pressure as the dependent variable, and 2) constant inflow pressure, with flow as the dependent variable. Isolated rat lungs were perfused at different baseline transvascular pressures. The experimental arrangement allowed changes between the two types of perfusion. Hypoxia at constant pressure perfusion gave a higher percentage rise in pulmonary vascular resistance (PVR) at all pressure levels. This advantage was however, more than offset by the finding that a) vascular closure (total or partial) often occurred, particularly below arterial pressure of 3 kPa, making detection of graded responses impossible, and b) the control situation was rarely regained. Responses obtained during constant flow were less reduced by elevations in baseline transvascular pressure, and the control situtaion was rapidly and completely regained. The observation that hypoxic vascular closure may occur in the pulmonary vascular bed supports the hypothesis that high altitude edema is caused by precapillary occlusion of a major part of the vascular bed, thereby subjecting still perfused regions to very high pressure and flow.

Hypoxic pulmonary vasoconstriction in the adult respiratory distress syndrome.

Increased pulmonary vascular resistance (PVR) and microvascular hyperpermeability resulting in lung edema and arterial hypoxemia are mainstays in the development of adult respiratory distress syndrome (ARDS). The proposed pathophysiologic mechanisms include activation of complement and polymorphonuclear leukocytes secreting lysosomal enzymes, toxic oxygen metabolites (TOM) and eicosanoids. Platelets and coagulation factors are also involved, and in the most severe cases even monocytes are activated as reflected in release of thromboplastin. The latter may elicit disseminated intravascular coagulation (DIC). Under physiologic conditions lung blood flow is diverted from poorly to better oxygenated areas by way of hypoxic pulmonary vasoconstriction (HPV), thereby counteracting a decrease in arterial oxygenation. Many vasoactive substances have been proposed and again refuted as possible mediators of HPV. In this study we have focused on the following: histamine, catecholamines, arachidonates, calcium, phosphoinositides and TOM as well as endothelium-derived relaxing and constricting factors. Whether HPV is present in ARDS and whether it is advantageous or not seems to depend on the stage and extent of disease. We discuss possible interactions between HPV and ARDS mediators and between HPV and various vasoactive agents tested for therapeutic effects. Out of the abundance of mediators released, prostacyclin, prostaglandin E1, activated complement and platelet activating factor have been shown explicitly to inhibit HPV whereas others are suspected of doing so. In therapeutical use, prostacyclin has proved to reduce PVR and at the same time enhance cardiac output and oxygen delivery. In mild to moderate ARDS, improvement of arterial oxygenation has also been obtained employing almitrine bismesylate, a potentiator of HPV. Experimentally, adenosine effectively reduces increments in PVR and microvascular permeability with modest effects on systemic circulation. However, further investigations are warranted to decide whether adenosine or more specific blockers as, for instance, monoclonal antibodies against tumor necrosis factor should be integrated in ARDS therapy in the future.

Increased microvascular permeability caused by toxic oxygen metabolites is partly reversed by exchanging the perfusate in isolated rat lungs.

Toxic oxygen metabolites (TOM) released from stimulated phagocytes and lung tissue have been shown to injure the pulmonary microcirculation. In the present study we evaluated microvascular injury caused by TOM in rat lungs perfused with plasma. The injury, as indicated by an increase in vascular permeability, was assessed by determining the fluid filtration rate (FFR) after paralysing the pulmonary vascular bed with papaverine (0.1 mg/ml). TOM were generated by adding xanthine oxidase (XO) (0.05-0.125 U/ml) and hypoxanthine (HX) (1 mmol/l) to the perfusate. FFR was measured before, 30 and 60 min after addition of XO and HX. The following interventions were done: 1. the H2O2-scavenger catalase, 2. substitution of the perfusate after 30 min, 3. BW 755 C, a combined lipoxygenase and cyclooxygenase inhibitor, and 4. indomethacin, a cyclooxygenase inhibitor. Addition of XO and HX caused FFR to increase from 14 +/- 4 mg/min (mean +/- s.e. mean) at the onset to 56 +/- 7 mg/min and 86 +/- 10 mg/min after 30 and 60 min, respectively. Replacing the perfusate with fresh plasma after 30 min caused a significant reduction in FFR at 60 min, from 86 +/- 11 mg/min to 58 +/- 10 mg/min. Catalase prevented the increase in FFR. Indomethacin and BW 755 C had no effect on the increase in FFR. We conclude that TOM induced a partly reversible increase in microvascular permeability of isolated rat lungs. From previous studies, the activity of XO was expected to cease after 30 min. Therefore it is suggested that secondary products of TOM propagate the lung injury. The increase in permeability was not mediated by arachidonic acid metabolites.

The pulmonary vasoconstrictor response to hypoxia during enflurane anesthesia.

Previous investigations have shown that diethyl ether, halothane and methoxyflurane inhibit the vasoconstrictor response to hypoxia in isolated rat lungs. A damping effect of diethyl ether and halothane has been observed in the human lung as well. In the intact dog lung, however, other workers have recently denied any effect of halothane and enflurane on this vasoconstrictor mechanism. These findings challenged us to investigate the effect of enflurane on the basoconstrictor response to hypoxia in isolated rat lungs. We found that enflurane administered via the airways reduced the response in proportion to the end-tidal concentration of enflurane, as determined by mass spectrometry.

Changes in blood volume and extravascular water content in isolated perfused rat lungs during ventilation hypoxia.

Isolated rat lungs were perfused with homologous blood at constant volume inflow. The effect of ventilation hypoxia on pulmonary vascular resistance, preparation weight and reservoir volume (vascular capacitance) were studied. In some experiments also wet/dry weight ratio of the preparation was estimated (extravascular water content). There was no difference in this last parameter between hypoxic and normoxic lungs, thus alveolar hypoxia had no effect on tissue water content as previously described in intact rats. With forward perfusion small and transient changes in either direction were seen in preparation weight and reservoir volume, even though inflow pressure exceeded 5 kPa during alveolar hypoxia. With backward perfusion marked weight increases were seen, and if inflow pressure in this situation was above 3.5 kPa, the weight change was irreversible, thus indicating outward fluid filtration. It is concluded that the vessels responding to alveolar hypoxia are located on the arterial side of the pulmonary vasculature.

Hypoxia-induced pulmonary vasoconstriction: effects of fentanyl following different routes of administration.

Recent investigations have revealed that intravenous anesthetics, including fentanyl, do not reduce the pulmonary vasoconstrictor response to alveolar hypoxia. In contrast, the response is markedly reduced or abolished by inhalation anesthetics. Recent investigations have demonstrated that the route of administration is of importance. Halothane, which inhibits the response when administered via the airways, behaves more like an intravenous anesthetic following administration via the blood stream, provided the alveolar concentration has been kept low (Bjertnaes et al. 1977). It was therefore a distinct possibility that the lack of any damping effect of fentanyl on the response could be due to the route of administration rather than to a different pharmacological property. We have tested this hypothesis by introducing fentanyl in nebulized form via the airways in one group of isolated rat lungs, and via the blood stream in another group. We found, however, no effect of fentanyl on the pulmonary vasoconstrictor response to hypoxia, regardless of the route of administration. Plasma concentrations of fentanyl were determined by radioimmunoassay and compared with those encountered in anesthetic practice.

Toxic oxygen metabolites reduce inactivation of prostaglandin E2 in isolated perfused rat lungs.

The metabolic function of the lungs may be impaired in acute lung injuries. The present work examined the effect of toxic oxygen metabolites (TOM) on the pulmonary clearance of prostaglandin E2 (PGE2). Isolated rat lungs perfused with plasma were exposed to TOM, generated by xanthine oxidase (XO) and hypoxanthine (HX) in the perfusate. Inactivation of PGE2 was determined by superfusion bioassay technique. XO and HX (n = 6) reduced the inactivation of PGE2 from 78 +/- 4% (mean +/- SE) to 61 +/- 3%. This reduction was inhibited by the free radical scavengers superoxide dismutase and catalase, as well as by allopurinol, an inhibitor of XO. Neither hydrostatic lung edema nor perfusion per se decreased the inactivation of PGE2. Lungs pretreated with indomethacin still showed impaired PGE2 inactivation after exposure to XO and HX, indicating that a possible release of PGE2-like substances did not influence our findings. This study indicates that TOM may impair pulmonary metabolic function as shown by reduced inactivation of PGE2.

The pulmonary vasoconstrictor response to hypoxia: effects of inhibitors of prostaglandin biosynthesis.

The main purpose of the present work was to determine whether prostaglandins (PGs) synthetised in the lungs mediate the vasoconstrictor response to acute alveolar hypoxia. Isolated and ventilated lungs of rats were perfused at 37 degrees C with homologous blood at constant-volume, pulsatile inflow, and pressor responses to 3 min periods of standardized ventilation hypoxia recorded. Indomethacin, sodium meclofenamate and acetylsalicylic acid (all 100 mug/ml), which are potent inhibitors of PG biosynthesis, did not reduce the hypoxic vasoconstrictor response. Sometimes they even enhanced this response. We conclude that PGs do not mediate the hypoxia-induced vasoconstriction. We suggest that vasodilatory PGs might act to reduce and modify pulmonary arterial hypertension due to hypoxia.

Allopurinol inhibits hypoxic pulmonary vasoconstriction. Role of toxic oxygen metabolites.

The exact mechanism whereby hypoxic pulmonary vasoconstriction (HPV) is elicited is still unsettled. We have evaluated a possible role for toxic oxygen metabolites (TOM), employing a set-up of blood-perfused isolated rat lungs. HPV reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/- 0.2 kPa to 3.2 +/- 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase (XO), allopurinol (AP) reduced the subsequent response to 2.5 +/- 0.2 kPa (P less than 0.001). By contrast, AP did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of XO). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on HPV; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that AP inhibition of XO depresses HPV. This could be due either to reduced production of TOM or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of TOM refutes a role for these metabolites in the elicitation of HPV. More likely, AP inhibits HPV by interfering with the purine metabolism.

The function of granulocytes and alveolar macrophages following a single dose of endotoxin in rabbits. Effects of methylprednisolone.

It is a generally held opinion that steroids attenuate the activation of phagocytes. However, this statement has its limitations; in rabbit endotoxemia, for instance, steroids enhance the procoagulant activity of monocytes. The present study aimed to investigate the release of toxic oxygen metabolites (TOM) from granulocytes and alveolar macrophages 24 h after endotoxin injection in rabbits, and the effect of concomitant injection of methylprednisolone (MP). Release of TOM was assessed by peak chemiluminescence (CLP). Expression of thromboplastin activity by alveolar macrophages was determined as well, employing a recognized method for assessment of activity. In terms of mean +/- s.e.mean, endotoxin increased granulocyte count from a baseline value of 1.8 +/- 0.2 X 10(6) cells/ml to 3.7 +/- 1 X 10(6) cells/ml, which increased further to 9.8 +/- 2.5 X 10(6) cells/ml following administration of MP. Whereas endotoxin given alone caused no significant change in granulocyte CLP, additional administration of MP increased CLP from 1723 +/- 389 to 16610 +/- 8428 counts. On the other hand, MP attenuated an endotoxin-induced increase in both CLP and thromboplastin activity of alveolar macrophages. Thus, MP appears to have a proinflammatory effect on circulating granulocytes in rabbit endotoxemia, simultaneously depressing the function of stationary macrophages. This may suggest an injurious effect of MP in rabbit endotoxemia.