Comparative bioavailability of Neoral and Sandimmune in cardiac transplant recipients over 1 year.
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Biomedical subjects
Publications and source records attributed to V Jeevanandam.
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BACKGROUND: Left ventricular assist devices (LVADs) are being used as bridges to heart transplantation (HT). Infection of the LVAD in this patient population represents a serious complication, as simple LVAD removal or delaying HT may result in death. To improve outcomes in this group of patients, we performed HT in the presence of LVAD infection. METHODS: Eighteen patients underwent LVAD implantation followed by HT. Ten underwent HT in the absence of LVAD infection (group 1); and 8, in the presence of LVAD infection (group 2). All patients were treated similarly except for modification of immunosuppression in group 2 patients. RESULTS: Infectious and noninfectious complications were equivalent between the two groups. There was no difference between groups in regard to intraoperative deaths (one versus none), long-term survival (8/10 versus 7/8), wound complications (three versus none), and mean length of hospital stay after HT (21 versus 26 days). CONCLUSIONS: Patients with LVAD infection are too seriously ill to allow LVAD removal or delay of HT. Transplantation in the face of infection is an effective treatment option.
OBJECTIVE: Thyroid hormone (3,5,3'-triiodo-L-thyronine is under investigation as a positive inotrope and vasodilator for patients undergoing cardiac surgery. This study determined the direct effects of triiodothyronine on human blood vessels. DESIGN: Prospective, controlled, in vitro study. SETTING: Laboratory facility in a university teaching hospital. PARTICIPANTS: Small excess segments of internal mammary arteries or saphenous veins were obtained from patients undergoing coronary artery bypass surgery. INTERVENTIONS: Vessel segments were cut into rings to measure isometric tension development in isolated tissue baths containing Krebs-Ringer bicarbonate solution at 37 degrees C. Rings were prestretched in vitro to resting tensions analogous to mean arterial or central venous pressures in vivo and then constricted with potassium or phenylephrine. Rings were exposed to increasing concentrations of triiodothyronine (4 x 10(-12) to 1 x 10(-4) mol/L) to obtain dose-response curves. MEASUREMENTS AND MAIN RESULTS: High concentrations (> or = 3.3 x 10(-5) mol/L) of trilodothyronine produced dose-dependent relaxation of preconstricted rings. The relaxation was not selective for arteries or veins at arterial resting tensions, and with either potassium or phenylephrine as a vasoconstrictor. Propranolol had little effect on subsequent triiodothyronine-induced relaxation of potassium-constricted rings at resting arterial tensions. CONCLUSIONS: Triiodothyronine, in supraphysiological and suprapharmacological concentrations, dilates preconstricted rings of human blood vessels in vitro; however, triiodothyronine had no demonstrable vasomotor effects on human internal mammary artery or saphenous vein in clinically relevant concentrations (10(-9) to 10(-8) mol/L). Triiodothyronine administration in vivo most likely has little direct effect on the tone of human vascular smooth muscle, particularly coronary artery bypass conduits.
Triiodothyronine (T3) deficiency, present in 85% of donors, in recipients with end-stage cardiomyopathy, and in patients after cardiopulmonary bypass (CPB), may contribute to donor heart dysfunction after heart transplantation (HT). Three separate studies were performed to investigate the various potential applications of T3 in HT. In the first study, donor hearts with statistically higher filling pressures, lower EF on echocardiograms, and higher inotrope requirements were resuscitated with T3 (0.6 microgram/kg bolus) and compared to normal donors not receiving T3. All patients survived the immediate postoperative period, and at 1 week and 6 months there were no significant differences in SBP, DBP, HR, cardiac index, CVP, PCWP, or LVEF on echocardiography. The next study involved giving T3 (0.6 microgram/kg bolus) versus placebo to normal donors in a blinded randomized fashion. Although there was a trend toward less inotrope use in the T3 group, there were no other differences. In the third study, placebo (group A) or T3 (group B; 0.2 microgram/kg bolus, 0.4 microgram/kg infusion over 6 hours) was given immediately before donor heart reperfusion. The recipient groups were similar with regard to age, donor/recipient weight ratio, ischemic time, thyroid hormone levels, and pretransplant hemodynamics. Lactate from coronary sinus effluent after 10 minutes of reperfusion was higher in group A, and more group A patients required higher than baseline inotropic support. In conclusion, T3 can be used effectively to resuscitate selective donor hearts with poor function and in recipients to improve myocardial aerobic metabolism; and T3 decreases both the amount and duration of inotropic support.
BACKGROUND: Vitamin K1 is used to reverse warfarin's anticoagulant action. It is unclear whether intravenous vitamin K1 is safe or efficacious prior to urgent cardiac surgery. METHODS: We retrospectively and prospectively examined the effects of preoperative intravenous vitamin K1 in vivo (administered for warfarin reversal immediately before heart transplantation) on intraoperative blood product utilization, hemodynamics and coagulation parameters. We also determined the direct effects of vitamin K1 in vitro on rings of human saphenous vein and internal mammary artery. RESULTS: In the retrospective limb, 29 of 67 patients were administered vitamin K1 preoperatively via slow intravenous infusion. Vitamin K1 administration produced no adverse outcome but did not affect subsequent perioperative use of blood products. In the prospective limb (n = 10), vitamin K1 significantly (P < or = 0.01, Student t-test) altered mean arterial pressure (from 85 +/- 15 to 76 +/- 16 mmHg), systemic vascular resistance (from 1364 +/- 308 to 1078 +/- 252 dyn.s.cm-5), and cardiac index (from 2.3 +/- 0.3 to 2.7 +/- 0.3 L/min/m2) (mean +/- SD). Significant decreases in prothrombin time (19.8 +/- 2.7 to 17.7 +/- 1.8 s) and activated clotting time (164 +/- 26 to 137 +/- 24 s) were observed at 60 min. In vitro vitamin K1 (10(-7) to 10(-4) M) had no effect on the tone of noradrenaline-constricted rings. CONCLUSIONS: Vitamin K1, administered by intravenous infusion prior to heart transplantation, did not alter subsequent perioperative blood product administration. Vitamin K1 rapidly reversed the anticoagulant effect of warfarin and produced modest hemodynamic changes. The decrease in systemic vascular resistance is probably not due to a direct effect of vitamin K1 on vascular smooth muscle.
BACKGROUND: Left ventricular assist devices (LVAD) provide lifesaving circulatory support to patients awaiting heart transplantation. To date, the extent to which sustained mechanical unloading alters the phenotype of pathologic myocardial hypertrophy in dilated cardiomyopathy is unknown. METHODS: We examined left ventricular size, myocyte and myocardial immunoreactivity for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in eight patients with advanced dilated cardiomyopathy before and after LVAD support. The mean duration of congestive heart failure was 18 +/- 5 months, and LVAD support averaged 42 +/- 4 days before heart transplantation. RESULTS: Echocardiographically determined left ventricular mass decreased from 505 +/- 83 to 297 +/- 52 gm (p < 0.05) during LVAD support, whereas minimum myocyte diameter decreased from 28.1 +/- 0.9 to 21.7 +/- 0.6 microns (p < 0.01) in transmural myocardial tissue specimens. Overall left ventricular ANP immunopositivity decreased from 48% at LVAD placement to 12% at transplantation (p < 0.05), whereas BNP immunopositivity decreased from 28% to 4% after LVAD support. Moreover, a gradient of ANP and BNP immunostaining from subendocardium to epicardium observed before mechanical unloading diminished after LVAD support. Analysis of the relationship between left ventricular mass and ANP immunopositivity revealed a close and highly significant correlation between these variables. CONCLUSIONS: These studies demonstrate remarkable left ventricular plasticity even in the presence of advanced cardiomyopathy. Parallel reductions in myocardial mass and myocyte size with reductions in ventricular ANP and BNP immunostaining indicate a novel regression of the phenotype of pathologic hypertrophy within the human myocardium after LVAD support.
BACKGROUND: Left ventricular assist devices (LVADs) have provided a new therapeutic option for patients with end-stage heart failure. Despite advances in device design, there remains an apparent bleeding diathesis, which leads to increased transfusion requirements and reoperative rates. The purpose of our study was to examine the abnormalities that might contribute to these clinical sequelae. METHODS AND RESULTS: To separate the effects of cardiopulmonary bypass (CPB), eight patients undergoing coronary revascularization (CABG) were compared with seven LVAD (TCI HeartMate) recipients intraoperatively and 2 hours postoperatively. We evaluated several well-characterized indexes of platelet activation: platelet count, platelet factor 4 (PF4), beta-thromboglobulin (beta-TG), and thromboxane B2 (TXB2). We also measured activation of thrombin: thrombin-antithrombin III (TAT), prothrombin fragment 1 + 2 (F1 + 2), and fibrinopeptide A (FPA) as well as markers of fibrinolysis: plasmin-alpha 2-antiplasmin (PAP) and D-dimer. Patterns of intraoperative platelet adhesion and activation were not statistically different in the CABG control and LVAD groups. In the immediate postoperative period, however, there was significant release of PF4 and beta-TG and generation of TXB2. Compared with the CABG controls (TAT, 26 +/- 8 micrograms/L; F1 + 2, 4 +/- 1 nmol/L; mean +/- SEM), there was a significant increase in TAT (380 +/- 112 micrograms/L) and F1 + 2 (23 +/- 4 nmol/L) in LVAD patients 2 hours after surgery. Furthermore, a sharp rise in FPA was noted 20 minutes after LVAD initiation (CABG, 8 +/- 4 ng/mL; LVAD, 235 +/- 63 ng/mL; P < .05). A concomitant increase in both PAP (CABG, 987 +/- 129 micrograms/L; LVAD 3456 +/- 721 micrograms/L; P < .05) and D-dimer (CABG, 1678 +/- 416 ng/mL; LVAD, 15243 +/- 4682 ng/mL; P < .05) was observed. CONCLUSIONS: The additive effects of CPB and LVAD lead to platelet activation as well as elevation of markers of in vivo thrombin generation, fibrinogen cleavage, and fibrinolytic activity. The etiology of these findings may be secondary to the LVAD surface, flow characteristics, and/or operative procedure. Nevertheless, platelet alterations and exaggerated activation of the coagulation and fibrinolytic systems may contribute to the clinically observed hemostatic defect.
BACKGROUND: Bradycardia and sinus node dysfunction are common causes of early postoperative morbidity in orthotopic heart transplant recipients and frequently require the use of chronotropic drugs or permanent pacemakers. Several causes have been postulated, including surgical trauma to the sinus node and its blood supply. We sought to eliminate sinus node dysfunction and postoperative bradyarrhythmias by altering the orthotopic heart transplantation technique. METHODS AND RESULTS: Seventy orthotopic heart transplant recipients underwent electrophysiological testing of sinus node function a mean of 9 +/- 3 days after surgery. Standard (atrial anastomosis) orthotopic heart transplantation was performed in 33 patients; total (bicaval anastomosis) heart transplantation was performed in 37 patients. Abnormalities of sinus node function were present in 14 of 33 patients (42%) undergoing standard orthotopic heart transplantation compared with 2 of 37 patients arrhythmia (5%) in whom total heart transplantation was performed (P < .005). The resting sinus heart rate of patients with a normal sinus rhythm was also significantly higher in the total heart transplantation group (90 +/- 12 versus 83 +/- 14 bpm, P < .05). Coronary angiography was performed before discharge in 63 patients. Eleven were found to have an abnormal sinoatrial nodal artery, and 7 of these patients also had evidence of sinus node dysfunction (P < .005). CONCLUSIONS: Surgical trauma to the donor sinus node and/or its blood supply is a significant cause of sinus node dysfunction in the orthotopic heart transplant recipient. By use of a bicaval anastomotic technique, the incidence of and need for treatment of postoperative bradyarrhythmias can be significantly reduced.
BACKGROUND: The lack of satisfactory donor organs limits heart transplantation. The purpose of this study was to determine whether the criteria for suitability of donors may be safely expanded. METHODS: One hundred ninety-six heart transplantations were performed on 192 patients at our institution from January 1992 to 1995 and were divided into two groups. Group A donors (n = 113) conformed to the standard criteria. Group B donors (n = 83) deviated by at least one factor and consisted of the following: 16 hearts from donors greater than 50 years of age, 33 with myocardial dysfunction (echocardiographic ejection fraction = 0.35 +/- 0.10, dopamine level exceeding 20 micrograms.kg-1.min-1, and resuscitation with triiodothyronine), 33 undersized donors with donor to recipient weight ratios of 0.45 +/- 0.04, 48 with extended ischemic times of 297.4 +/- 53.6 minutes, 25 with positive blood cultures, 16 with positive hepatitis C antibody titers, and 7 with conduction abnormalities (Wolff-Parkinson-White syndrome, prolonged QT interval, bifascicular block). RESULTS: Thirty-day mortality was 6.2% (7/113) in group A and 6.0% (5/83) in group B. Mortality in group A was attributed to 3 patients with myocardial dysfunction, 2 with infection, 1 with acute rejection, and 1 with pancreatitis; group B had 2 with myocardial dysfunction, 1 with infection, 1 with aspiration, and 1 with bowel infarction. At 12 months, survival and hemodynamic indices were similar between the groups. Of the 16 recipients with hepatitis C-positive hearts, 5 have become hepatitis C positive with mild hepatitis (follow up, 6 to 30 months). CONCLUSIONS: Expanding the criteria for suitability of donor hearts dramatically increases the number of transplantations without compromising recipient outcome.
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BACKGROUND: Heart transplantation is associated with excessive bleeding due to recipient coagulopathy, frequent need for reoperative median sternotomy, and prolonged cardiopulmonary bypass. Aprotinin reduces bleeding and the inflammatory response after cardiopulmonary bypass, but there are concerns about efficacy and side effects. METHODS: To determine the role of aprotinin in primary and reoperative sternotomy heart transplantation, we studied 70 patients undergoing heart transplantation between August 1993 and October 1994. Thirty-eight undergoing primary sternotomy for heart transplantation and receiving no aprotinin were randomized to group A (n = 20); patients in group B (n = 18) received the full recommended dose. Similarly, 32 patients undergoing reoperative heart transplantation were randomized to group C (n = 16), receiving no aprotinin, and to group D (n = 16), receiving aprotinin at the full recommended dose. All patients received the same immunosuppression regimen. Similarities in the groups included recipient age, weight, preoperative hemodynamic indices, creatinine, creatinine clearance, platelet count, hemoglobin, percentage receiving warfarin, prothrombin time, partial thromboplastin time, cardiopulmonary bypass time, and creatinine level at 48 hours. RESULTS: There were no significant differences postoperatively between groups A and B. Differences (p < 0.05) 24 hours postoperatively between groups C and D, respectively, included: total blood product requirement (5.9 +/- 3.8 versus 3.6 +/- 2.0 U), total fluid balance (+752 +/- 300 versus -250 +/- 185 mL), chest tube drainage (894 +/- 120 versus 526 +/- 95 mL), alveolar-arterial O2 difference (120.4 +/- 45.9 versus 95.5 +/- 33.5), and pulmonary artery mean pressures (28.2 +/- 4.6 versus 21.1 +/- 3.5 mm Hg). CONCLUSIONS: Aprotinin decreases bleeding after reoperative heart transplantation without renal dysfunction. Decreased inflammation is manifested as reduced fluid requirement and improved pulmonary and right heart function, which benefit patients during the posttransplantation period. Aprotinin at recommended doses is effective and safe for patients undergoing reoperative heart transplantation.
Although there is increasing evidence that mismatched donor HLA antigens are associated with a lowering of survival of human cardiac allografts, the effect of antibodies that bind those antigens is less clear. The existence of lymphocytotoxic antibodies prior to cardiac transplantation has been associated with a poor outcome in the majority of reports of relevant studies, as has their appearance post-transplantation. But how such antibodies, especially those with HLA specificity, cause poor outcomes has been poorly understood. The purpose of this study was to investigate the effect of anti-HLA antibodies appearing in the circulation after human orthotopic heart transplantation. Such antibodies were identified by a standard microlymphocytotoxicity technique using panels of frozen lymphocytes from normal donors who had been tissue typed. Of 74 patients transplanted over a 12-month period, 4 (5.4%) developed alloantibodies specific for mismatched donor HLA antigens. The first patient developed antibodies to HLA-A23 and B44 together with poor ventricular function and vascular rejection requiring retransplantation within 4 months. The other patients (3) developed antibodies specific for HLA-DQ antigens and experienced variable numbers of episodes of cellular rejection with no evidence of vascular rejection on endomyocardial biopsy. Two of these three patients died (8 and 11 months post-transplant) after three and six rejection episodes, respectively. The one surviving patient had seven rejection episodes and continues to have poor ventricular function 18 months post-transplant. We conclude that alloantibodies specific for mismatched donor HLA antigens may have a deleterious effect on the outcome of the human cardiac allograft and should be monitored closely post-transplant. Furthermore, such antibodies may mediate effects on the transplanted heart which are not detectable in specimens obtained by endomyocardial biopsy.
OBJECTIVES: This study analyzes our experience with transplantation of small donor hearts in a subgroup of moribund patients who could not be bridged to transplantation with mechanical assist devices. BACKGROUND: The major problem facing transplant programs in the United States is the lack of donor heart availability. One method of expanding the donor pool may be to liberalize the criteria for an acceptable donor heart. METHODS: We analyzed the growth and adaptation of 14 undersized and 14 conventionally sized donor hearts over a period of 10 weeks after heart transplantation. The left ventricular systolic and diastolic diameters, septal and posterior wall thicknesses, left ventricular mass calculated by the Penn convention and left ventricular ejection fraction were obtained by M-mode and two-dimensional echocardiography and documented by a single reader in blinded manner. Echocardiographic measurements were obtained before implantation and at 5 and 10 weeks after orthotopic heart transplantation. RESULTS: The mean (+/- SD) donor/recipient weight ratios were 0.53 +/- 0.06 for undersized hearts and 0.98 +/- 0.05 for normal-sized hearts. All 28 patients received similar immunosuppressive regimens, including intravenous steroids, cyclosporine and azathioprine. The length of hospital stay after transplantation did not vary significantly between the two groups. All the patients had at least one rejection episode during the 10-week study period. There was a tendency toward higher pulmonary pressures in undersized hearts, which was not statistically significant. Heart rate was significantly higher for undersized hearts, due in part to the use of theophylline or terbutaline to maintain tachycardia. There was a significant increase in left ventricular systolic and diastolic dimensions in undersized hearts compared with conventionally sized hearts. Undersized hearts increased in left ventricular mass over the 10-week period, whereas the conventionally sized donor hearts did not change between 5 and 10 weeks. CONCLUSIONS: In undersized hearts the increase in left ventricular mass and internal dimensions, with preservation of the posterior/septal wall thickness ratio, suggests that the left ventricle adapts to the larger recipient circulation early after transplantation. Despite denervation and a mismatched load, undersized transplanted hearts adapt appropriately to their new hemodynamic milieu.
OBJECTIVE: The authors review their experience and that of others who have reported cases in the literature on the surgical management of cardiac pheochromocytomas. SUMMARY BACKGROUND DATA: Cardiac pheochromocytomas are rare cathecolamine-producing tumors that can be densely adherent to myocardium. Because resection can be associated with significant morbidity, we sought to determine the best mode of treatment for these difficult tumors. METHOD: The authors reviewed the experience for management of cardiac pheochromocytomas in their two institutions and those reported in the literature. Follow-up was available for 21 of 26 patients up to 9 years after resection. RESULTS: Twenty-five patients had reconstruction of the native heart; five (20%) died intraoperatively from hemorrhage, one (4%) died postoperatively from sepsis, three (12%) sustained myocardial infarction, one (4%) required a mitral valve replacement, and three (12%) had incomplete resections, two of whom subsequently developed metastatic disease and died. One patient, thought to be a high risk for resection, received an orthotopic heart transplantation. CONCLUSIONS: Surgical resection of cardiac pheochromocytomas can be performed successfully. However, resection of lesions that aggressively invade adjacent myocardium is associated with significant mortality and inadequate control of the neoplasm. Cardiac transplantation should be available as an option before embarking on resection, and it should be performed if mandated by intraoperative findings.
Methylmethacrylate bone cement is associated with severe hypotensive reactions during surgery and anesthesia. The purpose of this in vitro study was to determine if methylmethacrylate monomer could produce hypotension by acting directly on vascular smooth muscle. Segments of human saphenous vein or rabbit thoracic aorta were cut into rings. The rings were mounted in isolated tissue chambers in order to measure isometric tension development. Methylmethacrylate monomer (methylmethacrylic acid ester) produced direct relaxation of venous or aortic rings preconstricted with either potassium ion or noradrenaline. The relaxation was concentration-dependent, occurring at concentrations from 10(-3) to 10(-1) M. The relaxation of rabbit aortic rings (preconstricted with noradrenaline) was unaffected by pre-treatment with atropine, propranolol, cimetidine, indomethacin, or methylene blue. Endothelial stripping with Triton X-100, sufficient to completely abolish acetylcholine-induced relaxation, also had little effect on methylmethacrylate-induced relaxation. Methylmethacrylate produced direct relaxation of rabbit aortic rings constricted with either potassium or noradrenaline in calcium-deficient media, and inhibited subsequent calcium-induced constriction. These results suggest that methylmethacrylate monomer may interfere with intracellular and extracellular calcium mobilization and excitation/contraction coupling in vascular smooth muscle. The direct relaxation of venous and arterial smooth muscle produced by methylmethacrylate monomer may contribute in part to the hypotension that can occur when acrylic bone cement is employed during orthopedic procedures.
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BACKGROUND: Because of the critical shortage of adult donor hearts, many recipients die awaiting transplantation of an organ of appropriate size. Undersized hearts (donor/recipient weight ratio < 0.7) have been used for heterotopic heart transplantation. We report on 6 moribund adult heart transplant candidates who were rescued with orthotopic heart transplantation of undersized pediatric hearts. METHODS AND RESULTS: Recipients were hypotensive (mean blood pressure, 62.3 +/- 13.4 mm Hg), had high pulmonary artery pressures (mean pulmonary artery pressure, 42.4 +/- 6.3 mm Hg), and had mean cardiac indexes of 1.7 +/- 0.6 L.min-1.m-2. Four had pretransplant intra-aortic balloon pumps, and one was on a Thoratec left ventricular assist device complicated by fungemia. Since conventionally sized donors were unavailable (+/- 30% recipient weight), the patients were listed in a wider weight range (+/- 60%). Donor characteristics were age, 8.7 +/- 1.5 years; weight, 32.8 +/- 7.0 kg; and donor/recipient weight ratio, 0.44 +/- 0.2, with average ischemic time of 236.0 +/- 59.3 minutes. Technical considerations during transplantation included (1) opening the donor right atrium from the inferior vena cava to superior vena cava to facilitate size matching, (2) performing size-mismatched pulmonary artery and aortic anastomoses end to end, (3) infusing prostaglandin E1 12 ng.kg-1.min-1 to decrease pulmonary and systemic vascular resistance, (4) pacing donor and recipient atria synchronously to improve ventricular filling, (5) maintaining high heart rates up to 140 beats per minute (initially with isoproterenol or pacing, chronically with theophylline), (6) hyperventilating with sedation and paralysis as necessary, (7) reperfusing with triiodothyronine, and (8) minimizing afterload. All patients were discharged from the hospital. At 1 week, hemodynamics were normal and echocardiograms demonstrated left ventricular growth. CONCLUSIONS: Hence, undersized pediatric hearts can be used successfully to salvage moribund patients and expand the potential donor pool for adult orthotopic heart transplantation.
Although activation of formed blood elements during cardiopulmonary bypass has been examined, its presumed procoagulant role has not been identified or quantified. We evaluated the effects of iloprost, an inhibitor of platelet and leukocyte function, on subclinical coagulation during simulated extracorporeal circulation. We determined that a heparin dose of 1 U/ml prevented clot formation in this model, but resulted in elevated plasma levels of fibrinopeptide A, the first cleavage product of fibrinogen. Human blood was recirculated with 1 U/ml heparin using a roller pump and pediatric reversed hollow fiber oxygenator (0.8 m2) for 2 hr at 37 degrees C. Iloprost (1 ng/ml, n = 5) reduced platelet adhesion, with platelet counts of 78 +/- 7% (mean +/- SEM) of baseline during 2 hr of simulated extracorporeal circulation, compared to 36 +/- 6% in control circuits (CONT: n = 6, P < 0.05). Plasma levels of platelet factor 4 and beta-thromboglobulin were also reduced by iloprost (486 +/- 116 ng/ml vs CONT, 2933 +/- 275 ng/ml, P < 0.05, and 938 +/- 274 ng/ml vs CONT, 5700 +/- 1109 ng/ml, P < 0.05, respectively). Circulating leukocyte counts were maintained in iloprost circuits (6.4 +/- 0.6 x 10(3)/mm3 vs CONT, 4.2 +/- 0.3 x 10(3)/mm3, P < 0.05), and neutrophil elastase levels rose to only 0.4 +/- 0.1 ng/ml in iloprost circuits, compared to 0.8 +/- 0.1 ng/ml in CONT (P < 0.05). Finally, iloprost treatment reduced fibrinopeptide A levels to 102 +/- 28 ng/ml (CONT, 793 +/- 337 ng/ml, P < 0.05) after 2 hr.(ABSTRACT TRUNCATED AT 250 WORDS)