280 ABSTRACTS

with ARDS was inhibited by concanavalin A, an inhibitor of tissue factor. The hydrolysis of purified human factor X by BAL from the ARDS and other patient groups was deter- mined by measuring the amidolytic activity of generated factor Xa on its N-benzoyl-L-isoleucyl-L-glutamyl-glycyl- L-arginine-p-nitroanilide substrate. The procoagulant activ- ity of BAL was associated with the development of amido- lytic activity, indicating activation of factor X. BAL from patients with ARDS contained more factor X activating activity than did BAL from control groups (p < 0.001). This activity was calcium dependent and was maximal at 1 mM ionized calcium. The BAL factor X activating activity was most active at neutral pH and was sedimented by ultracentri- fugation at 100,000 x g. Cleavage of purified human ‘*‘I- labeled factor X by ARDS was demonstrated by SDS- polyacrylamide gel electrophoresis and autoradiography. The appearance of a 55,000 M, cleavage product, identical to factor Xa produced by activation of human factor X by Russell’s viper venom, strongly correlated with simulta- neously performed amidolytic determinations of factor Xa formed by activation of factor X by BAL. The activation of factor X by BAL was dependent on tissue factor and factor VII, since activation was inhibited by monospecific antibod- ies to human factor VII and tissue factor. Immunoblots demonstrated the presence of both tissue factor and factor VII in BAL from patients with ARDS. These studies demon- strate that increased procoagulant activity occurs in BAL from patients with ARDS, that procoagulant activity in unconcentrated BAL from patients with ARDS may activate factor X, and that the activation of factor X by BAL is effected mainly by a complex of tissue factor and factor VII. Augmented activity of the extrinsic coagulation pathway may occur in the alveolar compartment during human inflammatory lung injury and could contribute to extravascu- lar fibrin deposition in ARDS. (Reprinted with permission.)

The Adult Respiratory Distress Syndrome: Cell Populations and Soluble Mediators in the Air Spaces of Patients at High

Risk. Fowler AA, Hyers TM, Fisher EJ, Bechard DE, Centor RM, Webster RO. Am Rev Respir Dis 136:1225, 1987

In order to better understand the modulation of polymor- phonuclear neutrophil influx into the lung during the devel- opment of the adult respiratory distress sydrome (ARDS), we evaluated bronchoalveolar lavage fluids from control subjects (n = 9), patients at high risk of developing ARDS (n = 12), and patients with ARDS (n = II) for cellular and protein content and capacity to promote neutrophil adhesion to tissue culture plastic. Analysis of the lavage fluids from high risk patients and patients with ARDS showed an 8 to IO-fold increase in the total number of cells, an increase in the percentage of neutrophils present (control subjects = 1 f 0.4%. high risk = 53 + 8%, ARDS = 70 + 7%) and a IO- to 40-fold increase in protein content. The adherence of normal neutrophils to plastic surfaces after pretreatment with either concentrated lavage fluid, ultrafiltrates of BALF, or plasma samples was determined to evaluate the neutrophil adherence-promoting activity of each. Lavage fluid from high risk patients and patients with ARDS promoted an approximate 3-fold increase in neutrophil adherence when compared with control lavage fluid. Neutrophil adhesion- promoting activity of the plasma and lavage filtrates (mw

1500 daltons) was not significantly different from that of control subjects. The adherence-promoting activity found in ARDS lavage was stable at 56OC for 30 min. Higher temper- atures (1 OOOC) and exposure to trypsin or rabbit antihuman- CSa reduced, but did not abolish, activity. These results indicate that neutrophil influx into the air spaces and perme- ability changes in patients at high risk for ARDS occur prior to development of the syndrome. Further, substances capable of enhancing neutrophil adhesion are present in the air spaces, but not in plasma, prior to the onset of ARDS. These substances share both lipid and protein characteristics. (Re- printed with permission.)

Effect of Almitrine on Ventilation-Perfusion Distribution in Adult Respiratory Distress Syndrome. Reyes A, Rota J, Rodriguez-Roisin R, Torres A. Ussetti P, Wagner PD. Am Rev Respir Dis 137:1062, 1988.

Almitrine improves ventilation/perfusion relationships (VA/Q) in COPD, but its effects in ARDS, in which VA/Q

mismatching is the cause of severe hypoxemia, are not known. The effects of almitrine on pulmonary gas exchange and circulation were assessed in 9 patients with ARDS who were sedated, paralyzed, and mechanically ventilated at constant Flo, (range, 0.48 to 0.74). Systemic and pulmonary hemodynamics, conventional gas exchange, and the VA/Q

distribution by the multiple inert gas elimination technique (MIGT) were measured before (baseline), during (ALM 15). at the end of (ALM 30), and at 30-min intervals after (POSTALM 30,60, and 90) the intravenous infusion of 0.5 mg/kg body weight of almitrine over 30 min. Almitrine significantly increased PaoZ from 78 + I5 mm Hg to 140 + 49 at ALM 15 and 138 + 52 at ALM 30. AaP,, and @/OT decreased during the administration of the drug. The MIGT showed that almitrine redistributed pulmonary blood flow from shunt areas (reduction from 29 t 11 to I7 + 11%’ of QT) to lung units with normal VA/Q ratios (increase from 63 k 9 to 73 k 6% of QT). The Ppa increased from 26 + 5 to 30 + 5 mm Hg without changes in QT. Changes were transient, returning toward baseline 30 min after stopping the infusion of the drug. Almitrine significantly reduced the VA/Q inequalities present in ARDS and may be useful in the management of those patients. (Reprinted with permission.)

Pulmonary Vascular Tone Improves Pulmonary Gas

Exchange in the Adult Respiratory Distress Syndrome.

Melot C, Naeije R. Mols P, Hallemans R, Lejeune P. Jaspar N. Am Rev Respir Dis 136: 1232, 1987.

Hemodynamics, blood gases, lung mechanics, and the distributions of ventilation-perfusion ratios (VA/Q) were studied before and after iv diltiazem, 0.5 mg/kg over 30 min. in 6 patients with pulmonary hypertension secondary to the adult respiratory distress syndrome (ARDS) ventilated with 7 to 20 cm H,O positive end-expiratory pressure (PEEP). Diltiazem decreased systemic and pulmonary arterial pres- sures without changes in cardiac output and in filling pres- sures of the heart, and with a slowing of heart rate. Pulmo- nary vascular resistances decreased from 401 k 59 to 329 f 58 dyne . s . cm-‘. m* (mean i SEM), p <: 0.01. Arterial PO, decreased from 87 + IO to 80 + 1 I mm Hg (p < 0.02) without changes in arterial PCO*, mixed venous PO*, and 0,

ABSTRACTS 281

consumption. Lung compliance and airway resistances did not change. Diltiazem increased true shunt from 23 i- 5 to 30 + 7% of total blood flow (p < 0.02) without other moditi- cation in the pattern of VA/Q distribution as measured by the multiple inert gas elimination technique. These results sug- gest that pulmonary vascular tone contributes to the mainte- nance of VA/Q matching in patients with ARDS. (Reprinted with permission.)

Depressed Left Ventricular Performance: Response to Vol- ume Infusion in Patients With Sepsis and Septic Shock.

Ognibene FP, Parker MM, Natanson C, Shelhamer JH. Parrillo JE. Chest 93:903, 1988.

Volume infusion, to increase preload and to enhance ventricular performance, is accepted as initial management of septic shock. Recent evidence has demonstrated depressed myocardial function in human septic shock. We analyzed left ventricular performance during volume infusion using serial data from simultaneously obtained pulmonary artery cathe- ter hemodynamic measurements and radionuclide cineangi- ography. Critically il l control subjects (n = 14), patients with sepsis but without shock (n = 21), and patients with septic shock (n = 21) had prevolume infusion hemodynamic mea- surements determined and received statistically similar vol- umes of fluid resulting in similar increases in pulmonary capillary wedge pressure. There was a strong trend (p = 0.004) towards less of a change in left ventricular stroke work index (LVSWI) after volume infusion in patients with sepsis and septic shock compared with control subjects. The LVSWI response after volume infusion was significantly less in patients with septic shock when compared with critically il l control subjects (p < 0.05). These data demonstrate signifi- cantly altered ventricular performance, as measured by LVSWI, in response to volume infusion in patients with septic shock. (Reprinted with permission).

A Community-Wide Assessment of the Use of Pulmonary Artery Catheters in Patients With Acute Myocardial Infarc- tion. Gore JM. Goldberg RJ, Spodick DH, Alpert JS. Dalen JE. Chest 92:721, 1987.

As part of an on-going population-based study of patients hospitalized with acute myocardial infarction (Ml) in all 16 hospitals in the Worcester, Massachusetts Standard Metro- politan Statistical Area, temporal trends in the use of the pulmonary artery (PA) catheter were examined. Three thou- sand two hundred and sixty-three patients with validated acute MI during the calendar years 1975, 1978, 1981 and 1984 comprised the study population. There has been a consistent and significant increase in PA catheter use in patients with acute MI over time, from 7.2 percent in 1975, 13.8 percent in 1978, 14.8 percent in 1981 to 19.9 percent in 1984 (p < ,001). Ninety-six percent of patients undergoing PA catheter investigation had either congestive heart failure (CHF), hypotension or cardiogenic shock. For the combined time periods, the in-hospital case fatality rate (CFR) for patients in CHF with a PA catheter was 44.8 percent compared to 25.3 percent for patients without a PA catheter (p < ,001). For patients with hypotension and a PA catheter, in-hospital CFR was 48.3 percent compared to 32.2 percent for hypotension patients not receiving a PA catheter

(p < ,001). In contrast, for patients in cardiogenic shock the in-hospital CFR was 74.4 percent for those receiving a PA catheter as compared to 79.1 percent for patients in shock not receiving a catheter. The use of a PA catheter was associated with an increased length of hospital stay irrespective of the development of acute clinical complications. Long-term prog- nosis for discharged hospital survivors who had a complicated MI, for up to a five-year follow-up period was similar whether the patient did or did not receive a PA catheter during the acute period of hospitalizaiton. In conclusion, we could not demonstrate a beneficial effect associated with the use of the PA catheter on selected patient outcomes, includ- ing in-hospital and long-term prognosis and average hospital stay, in this community-wide study of patients hospitalized with acute MI. (Reprinted with permission.)

Treatment of Massive Acute Pulmonary Embolism: The Use

of Low Doses of lntrapulmonary Arterial Streptokinase Combined With Full Doses of Systemic Heparin. Leeper KV Jr, Popovich J Jr, Lesser EA. Adams D, Froelich JW, Burke MW, Shetty PC, Thrall JH, Stein PD. Chest 93:234, 1988.

The efficacy of low-dose, locally administered streptoki- nase (SK) combined with full therapeutic systemic doses of heparin was investigated. Seven patients with angiographi- tally proven massive acute pulmonary embolism were treated. Streptokinase, 1 O,OOO-20,000 units/hour, was administered directly into the left or right pulmonary artery for 9 to 24 hours. Heparin was administered concurrently. The number of unperfused segments of the infused lung shown on the lung scan decreased from 5 + 2 to 2 I 1 after 12-24 hours (p < .Ol). No change was shown in the contra- lateral lung. The angiographic index of severity score in the infused lung decreased from 16 f 1 to 9 _t 4 (p < .Ol). The partial pressure of oxygen in arterial blood improved within four hours. In spite of the low doses of streptokinase, however, two major bleeding episodes occurred that required blood transfusion. In conclusion, low dose intrapulmonary strepto- kinase, combined with intravenous heparin, may provide a therapeutic option in patients with life-threatening massive acute pulmonary embolism in whom full dose lytic therapy may be hazardous, although even low dose lytic therapy was associated with risk. (Reprinted with permission,)

Relationships of Oxygen Uptake and Oxygen Delivery in Respiratory Failure Not Due to the Adult Respiratory Dis- tress Syndrome. Dorinsky PM, Costello JL, Gadek JE. Chest 93:1013, 1988.

Previous studies have suggested that oxygen uptake (‘ire,) may be dependent on oxygen delivery (Qo,) at most levels of Qo, in patients with the adult respiratory distress syndrome (ARDS); however, the adequacy of substrate delivery in patients with non-ARDS respiratory failure is unclear. The purpose of the present study was to examine the relationship between ire, and Qo, in a group of critically il l patients (n = 10) with non-ARDS respiratory failure (ie, cardiac pulmonary edema, chronic obstructive pulmonary disease [COPD], or pneumonia). For comparison, these relationships were also examined in a group of patients (n = 6) with ARDS. The data indicate that 00, is dependent on Qo, in both patients with ARDS and non-ARDS respiratory failure.