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Biomedical subjects

V P Addonizio

Publications and source records attributed to V P Addonizio.

At least 19 recordsLinked to original sources
PubMed1995

Effect of bullectomy on diaphragm strength.

Surgical removal of bullous lesions in selected patients with chronic obstructive pulmonary disease may significantly improve lung function, gas exchange, and functional status and reduce dyspnea. Proposed mechanisms by which bullectomy may produce these beneficial effects include (1) improving ventilation and perfusion matching by allowing compressed viable lung to re-expand and participate in gas exchange; (2) restoring outward elastic tension on small airways, thereby reducing airways obstruction; and (3) reducing end-expiratory lung volume, thereby diminishing the adverse effects of chronic hyperinflation on chest wall elastic recoil and inspiratory muscle force generation. In this report, we demonstrate the effect of bullectomy on transdiaphragmatic pressure generation, gas exchange, and exercise capacity in a patient with severe bullous emphysema who underwent unilateral bullectomy.

Adult↗
PubMed1994

Adult orthotopic heart transplantation using undersized pediatric donor hearts. Technique and postoperative management.

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.

Body Constitution↗
PubMed1993

Iloprost reduces procoagulant activity in the extracorporeal circuit.

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)

Blood Coagulation↗
PubMed1991

Cyclosporin A augments human platelet sensitivity to aggregating agents by increasing fibrinogen receptor availability.

Clinical use of cyclosporin A (CsA) has been associated with platelet hypersensitivity and an increased incidence of thrombotic and vasoactive events. The purpose of this study was (1) to confirm that CsA enhances platelet sensitivity to the soluble agonists, adenosine diphosphate (ADP) and epinephrine (EPI), and (2) to determine if this enhancement is mediated by alteration in the availability of platelet surface fibrinogen receptors, a final mediator of platelet activation. Mean log dose of ADP required to achieve complete second-wave platelet aggregation in vitro decreased from 1.90 to 1.49 microM (n = 19, paired t test, P less than 0.05) and 2.86 to 2.11 microM (n = 16, P less than 0.05) following a 15-min and 3-hr incubation in the absence (saline) and presence of CsA (1000 ng/ml), respectively. At the threshold dose of ADP, concurrent thromboxane B2 levels at 15 min were 245 +/- 44 ng/ml (n = 12, saline) and 265 +/- 54 ng/ml (n = 9, CsA; P greater than 0.05). At 3 hr respective levels were 333 +/- 57 and 442 +/- 81 ng/ml (P greater than 0.05). Similar results were obtained with EPI. The number of fibrinogen binding sites in response to 50 microM ADP was determined in washed platelets in the absence and presence of CsA by radioligand binding. In 6 of 7 volunteers, CsA increased fibrinogen receptors from 26,635 +/- 4841 to 35,925 +/- 7290 sites/platelet (means +/- SEM; P less than 0.05). No change in receptor affinity was noted. In conclusion, cyclosporine does augment platelet reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1991

Effects of simulated extracorporeal circulation on human leukocyte elastase release, superoxide generation, and procoagulant activity.

Activated leukocytes are thought to contribute to respiratory dysfunction, alterations in microvascular permeability, disseminated intravascular coagulation, and thrombosis, all of which can complicate extracorporeal circulation. The purpose of this work was to determine the effects of extracorporeal circulation on leukocyte functions likely to mediate organ damage. White blood cell counts in the bubble circuits (n = 5) fell to 51% +/- 7% (mean +/- standard error of the mean; p less than 0.05) of initial levels within 2 hours of recirculation. In contrast, counts from both the spiral coil (n = 5) and hollow-fiber (n = 5) groups remained at 91% +/- 12% and 100%, respectively. Plasma levels of human neutrophil elastase rose from 0.28 +/- 0.06 micrograms/ml to 3.14 +/- 0.36 micrograms/ml (p less than 0.05) and 0.20 +/- 0.02 micrograms/ml to 1.61 +/- 0.35 micrograms/ml (p less than 0.05) in bubble and spiral coil circuits, respectively, but from only 0.20 +/- 0.03 micrograms/ml to 0.96 +/- 0.42 micrograms/ml in the hollow-fiber circuit despite 2 hours of recirculation. Consistently, in response to N-formyl-L-methionyl-L-leucyl-L-phenylalanine, a chemotactic peptide, cells from spiral coil and bubble circuits released and generated significantly less elastase and superoxide anion, respectively. In contrast, neutrophils from the hollow-fiber circuits demonstrated enhancement of N-formyl-L-methionyl-L-leucyl-L-phenylalanine-induced elastase release and superoxide generation. Finally, mixed leukocytes from all circuits expressed procoagulant activity reaching statistical significance in bubble circuits. In conclusion, extracorporeal circulation has pronounced effects on neutrophil elastase release, superoxide anion generation, and leukocyte procoagulant activity. Spiral coil and bubble oxygenators cause granule release and, subsequently, reduced sensitivity to soluble agonists. In contrast, hollow-fiber oxygenators "prime" cells, actually enhancing reactivity. Recirculation through all circuits induces leukocyte procoagulant activity that is likely to contribute to surface-induced thromboses and excessive bleeding.

Blood Coagulation↗
PubMed1990

Intraoperative management of patients with heparin-induced thrombocytopenia.

For 11 patients with confirmed heparin-induced thrombocytopenia, we used reversible platelet inhibition with iloprost, a stable prostacyclin analogue, to permit safe heparin administration for cardiac (n = 9) or vascular (n = 2) operations. In vitro, iloprost (0.01 mumol/L) prevented both heparin-induced platelet aggregation and 14C-serotonin release in all patients. Therefore, intraoperatively, a continuous infusion of iloprost was started before administration of heparin and was continued until 15 minutes after administration of protamine. For cardiac patients, after heparin administration, the whole blood platelet count did not change (171,000 +/- 29,000/microL versus 174,000 +/- 29,000/microL, mean +/- standard error of the mean); no spontaneous platelet aggregation was observed, and plasma levels of the alpha-granule constituents platelet factor 4 and beta-thromboglobulin increased from 38 +/- 14 and 140 +/- 18 ng/mL to 591 +/- 135 and 235 +/- 48 ng/mL, respectively. Fibrinopeptide A levels actually decreased from 287 +/- 150 to 27 +/- 6 ng/mL. Furthermore, adenosine diphosphate-induced platelet activation was preserved, postoperative bleeding times were unchanged, and no heparin-related deaths occurred. Similar results were obtained in both vascular patients. We conclude that temporary platelet inhibition with iloprost now permits safe heparin administration in all patients with heparin-induced thrombocytopenia who require a cardiac or vascular operation.

Adult↗
PubMed1990

Platelet function in cardiopulmonary bypass and artificial organs.

Extensive contact between blood and synthetic surfaces is associated with both quantitative and qualitative changes in platelet function. Cardiopulmonary bypass is associated with a decline in the circulating platelet count, release of platelet alpha granules and possibly platelet dense and lysosomal granule release, and a prolongation of the bleeding time. It is assumed that these platelet alterations contribute to postoperative blood loss and reoperation for bleeding. Improvements in technology have reduced but not eliminated the adverse platelet changes. Temporary inhibition of platelet function during surface contact has achieved additional improvement in the setting of heparin-induced thrombocytopenia but is not yet suitable for "routine" open heart surgery. Long-term cardiopulmonary bypass or extracorporeal circulation membrane oxygenation is receiving increased use during acute respiratory insufficiency. Systemic anticoagulation is required. Bleeding and platelet consumption continue as clinical problems and are treated by repeated platelet transfusion. Because no air interface is present in this setting and the synthetic surface is homogeneous this would appear to be the ideal area for application of platelet functional inhibition and synthetic surface passivation to reduce platelet consumption. Although still under review by the Food and Drug Administration, pulsatile devices, including the total artificial heart, increasingly are being used to provide temporary support for the failing heart. Furthermore, it is likely that totally implantable devices will become available in the very near future. Considering that thromboembolism is a major problem for recipients of mechanical valves, it is likely that thromboembolism will persist as a limiting factor in the further implementation of pulsatile devices. It is assumed that imaginative antithrombotic therapy will be required and that platelet activation will be fundamental to the thrombotic process. Platelet behavior in this setting, however, remains incompletely characterized. The analytical methodology that has been used to assess platelet behavior during cardiopulmonary bypass should be applied to the pulsatile devices as well and results correlated with clinical problems. This should permit standardization of antithrombotic therapy and rational use of platelet functional inhibition.

Assisted Circulation↗
PubMed1989

Cardiac ischemia and endothelial function in the isolated rabbit heart.

Truly effective prevention of reperfusion myocardial damage is precluded in part by a lack of understanding of the earliest events which accompany ischemia. The purpose of this study was to assess the coronary endothelial response to two forms of ischemic injury in an isolated crystalloid perfused rabbit heart. Global cardiac ischemia, confirmed by NADH fluorescence photography, was induced either by mechanically reducing coronary flow by 90% (MRCF, N = 11) or by an infusion of N-formyl-methionyl-leucyl-phenylalanine (fMLP, N = 11), a known stimulus for leukotriene synthesis and coronary vasospasm. Compared with control, MRCF resulted in an increase in effluent concentrations of both prostacyclin (152 +/- 22 pg/ml vs 951 +/- 214 pg/ml, P less than 0.05) and plasminogen activator (0.8 +/- .3 IU/ml vs 1.4 +/- 0.5, P less than 0.05) but no detectable increase in effluent thromboxane B2 or leukotriene C4 concentrations. fMLP infusion resulted in an immediate reduction in coronary flow coincident with diffuse myocardial ischemia. In contrast to MRCF, however, fMLP-induced ischemia resulted in a significant but smaller increase in effluent prostacyclin concentration (210 +/- 47 pg/ml vs 606 +/- .55 pg/ml, P = 0.05) and a marked increase in both thromboxane B2 (less than or equal to 33 +/- 4 pg/ml vs 1141 +/- 375 pg/ml, P less than 0.05) and leukotriene C4 (less than 0.25 ng/ml vs 3.3 +/- 1.2 ng/ml, P less than 0.05) concentrations. Additionally, fMLP caused a reduction in effluent plasminogen activator activity (0.5 +/- 0.1 IU/ml vs 0.39 +/- 0.1 IU/ml, N = 4).(ABSTRACT TRUNCATED AT 250 WORDS)

6-Ketoprostaglandin F1 alpha↗
PubMed1989

Heparin-induced platelet activation: the role of thromboxane A2 synthesis and the extent of platelet granule release in two patients.

Heparin-induced thrombosis is due to an immune-mediated activation of circulating platelets and has significant clinical implications for patients with vascular disease. The purpose of this article was (1) to define the biochemical mechanisms of heparin-induced platelet activation (HIPA) and (2) to determine the relationship between thromboxane A2 (TxA2) synthesis and platelet granule release. In two patients with confirmed HIPA, heparin (3 U/ml) induced extensive platelet aggregation (61.5%), release of 14C-serotonin (81.5% of releasable 14C-serotonin, a dense granule marker) and platelet factor 4 (63.7% of releasable platelet factor 4, an alpha granule marker) and generation of TxB2, a stable metabolite of TxA2 (100% relative to serum control). In one patient heparin did not induce release of n-acetyl-beta-glucosaminadase (N-AC, a lysosomal granule marker), and aspirin (4 mmol/L), which abolished TxA2 synthesis, prevented aggregation and granule release. In the second patient heparin did induce release of N-AC (39.7% of releasable N-AC) and aspirin, despite abolishing TxA2 synthesis, did not prevent aggregation or granule release. In contrast, by elevating intracellular cyclic adenosine monophosphate, iloprost (0.01 mumol/L), a stable prostacyclin analogue, prevented heparin-induced aggregation, granule release, and TxB2 generation in both patients. Thus we show (1) HIPA can proceed independently of TxA2 synthesis; (2) heparin in certain patients can release lysosomal hydrolases, thus mimicking strong platelet agonists such as thrombin; and (3) iloprost but not aspirin prevents HIPA regardless of the biochemical pathways involved.

Aged↗
PubMed1988

Temporary inhibition of platelet function with iloprost (ZK36374) preserves canine platelets during extracorporeal membrane oxygenation.

Contact between blood and artificial surfaces results in extensive quantitative and qualitative alterations in platelet function. We evaluated the efficacy of a brief infusion of iloprost (ZK36374), a stable analog of prostacyclin, in preventing these platelet changes during extracorporeal membrane oxygenation. Twelve nonsplenectomized male mongrel dogs (23 to 30 kg) were randomized to treatment (n = 6) and control (n = 6) groups. The treatment animals received an infusion of iloprost at a rate of 150 ng/kg/min with the infusion being terminated 30 minutes after the initiation of extracorporeal membrane oxygenation, despite the fact that all animals were maintained on extracorporeal membrane oxygenation for 3 hours. In the control group, platelet counts dropped to 54% +/- 8.9% (mean +/- standard error of the mean) of initial levels at 30 minutes of extracorporeal membrane oxygenation and gradually rose to 87.2% +/- 6.7% at 3 hours. In contrast, the platelet counts of the iloprost-treated dogs remained stable throughout extracorporeal membrane oxygenation at 98.3% +/- 4.2% of initial counts. Platelet reactivity toward adenosine diphosphate revealed a significant and permanent loss of platelet function in the control group (37.0% +/- 2.1% inhibition). In contrast, the iloprost group demonstrated significant inhibition of platelet reactivity (79.2% +/- 8.3%) during the iloprost infusion but a return to normal function (4.2% +/- 6.7% inhibition) after cessation of drug infusion which persisted throughout extracorporeal membrane oxygenation. Plasma levels of the platelet-specific protein thrombospondin rose progressively from 918 +/- 89 ng/ml to 1465 +/- 239 ng/ml (delta 548 +/- 179 ng/ml) at 30 minutes of extracorporeal membrane oxygenation, which indicates extensive release of platelet granule contents (p less than 0.05). In contrast, plasma thrombospondin levels in the iloprost group demonstrated no additional rise after cessation of the iloprost infusion. In conclusion, iloprost effectively preserves platelet number and function during extracorporeal circulation. The fact that its salutary effects outlast its presence in plasma suggests that prevention of initial platelet-synthetic surface interactions permits the appearance of reduced surface affinity for platelets and, thus, reduced synthetic surface thrombogenicity.

Animals↗
PubMed1987

Quantitation of platelet preservation with prostanoids during simulated bypass.

Extensive blood-synthetic surface interactions during cardiopulmonary bypass produce adverse platelet alterations that can contribute to excessive blood loss following open cardiac surgery. These platelet alterations can be reduced by temporary inhibition of platelet function. In order to define further an optimal method of platelet inhibition during blood-synthetic surface contact, we quantitated platelet functional and structural alterations that occur during simulated extracorporeal circulation (SEC) despite platelet inhibition with Iloprost (ZK) or PGE1. Five-hundred milliliters of fresh heparinized human blood were recirculated for 2 hr in a circuit consisting of silicone rubber components and a spiral coil membrane oxygenator. When blood was recirculated for 2 hr without drug, platelet counts fell significantly to 46 +/- 7% (mean +/- SEM) of initial levels (P less than 0.01); mean platelet volume decreased from 6.90 +/- 0.25 micron3 to 6.05 +/- 0.33 micron3 (P less than 0.01); platelet dispersion increased from 1.73 +/- 0.02 to 2.14 +/- 0.09 (P less than 0.01) and platelets no longer aggregated in response to epinephrine or thrombin. In contrast, when blood was recirculated with either ZK (0.003 microM) or PGE1 (0.3 microM), platelet counts were significantly preserved when compared to blood recirculated without drug (82 +/- 5% and 89 +/- 7%, respectively; P less than 0.01); mean platelet volume did not change; and dispersion only increased from 1.74 +/- 0.02 to 1.85 +/- 0.04 (P less than 0.05). However, following gel filtration, platelets recirculated with PGE1 always responded less than platelets merely incubated with PGE1 when challenged with either epinephrine (50 vs 75%, P less than 0.05) or thrombin (37 vs 65%, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1987

A practical approach to prosthetic valve endocarditis.

Prosthetic valve endocarditis (PVE) is an infrequent but dread complication, occurring in 1 to 2% of patients both early (less than 60 days) and late postoperatively. Diagnosis is always (99%) possible by two sets of blood cultures, but occasional exogenous causes of bacteremia may cloud the diagnosis, as will culture-negative cases of PVE and skin contaminants. With obvious exogenous sources of bacteremia, achieving sterile blood cultures after eradication of the noncardiac source permits discontinuation of antibiotics after two weeks. When skin contaminants are suspected, withholding antibiotics and obtaining two sets of blood cultures is recommended, because the bacteremia with PVE is continuous. Preventive measures, including perioperative antibiotics, are warranted but will probably not significantly reduce the low incidence of infection already achieved. The major cause of improved survival in recent years is earlier operation (valve rereplacement). This has been demonstrated in the last ten years and is absolutely indicated for major heart failure, ongoing sepsis, fungous etiology, valve obstruction, new-onset heart block, and unstable prosthesis by fluoroscopy.

Anti-Bacterial Agents↗
PubMed1987

Heparin-induced platelet activation in sixteen surgical patients: diagnosis and management.

Heparin-induced platelet activation (HIPA) is a syndrome associated with thrombocytopenia, intravascular thrombosis, and arterial emboli. We have evaluated 16 patients for presumed HIPA because of the occurrence of thrombocytopenia or a new thrombotic complication during heparin therapy. In this group, 16 thrombotic events occurred in 10 patients with a mortality rate of 18.8%. Diagnosis was confirmed in vitro by the demonstration of at least 20% platelet aggregation and/or 6% 14C-serotonin release after heparin (0.1 to 3 U/ml) was added to a mixture of patient platelet-poor plasma (PPP, two parts) and aspirin-free donor platelet-rich plasma (PRP, three parts). After heparin was discontinued, seven patients continued to have HIPA in their own PRP although it could no longer be observed in donor PRP. Iloprost, a potent prostacyclin analog that reversibly inhibits platelet activation, completely prevented HIPA and release in all of nine patients. Aspirin, an irreversible cyclooxygenase inhibitor, failed to prevent HIPA in four of these nine patients. In conclusion, HIPA is associated with an extremely high morbidity and mortality rate. Evaluation of the patients' PRP in response to heparin may improve the diagnostic sensitivity of this assay. Aspirin does not reliably prevent HIPA, which suggests participation of thromboxane-independent pathways. Thus, if further exposure to heparin is unavoidable, a more effective platelet inhibitor such as iloprost is required to reliably prevent in vivo HIPA.

Adult↗
PubMed1987

Comparison of equimolar concentrations of iloprost, prostacyclin, and prostaglandin E1 on human platelet function.

Prostaglandins E1 and I2 (PGE1 and PGI2) have been shown to be potent inhibitors of platelet aggregation. We compared the antiaggregatory effect of equimolar concentrations of these two agents with that of a newly synthesized prostacyclin analogue, iloprost, and measured the effects of these agents on intracellular levels of cyclic adenosine monophosphate (cAMP) in human platelets. In addition, because the platelet inhibitory properties of prostanoids are associated with increased vasoactivity, we assessed the effects of each prostanoid on coronary flow in isolated perfused rat hearts. Concentrations ranging from 0.0001 mumol/L to 1 mumol/L of iloprost, PGI2, and PGE1 were incubated with either platelet-rich plasma or gel-filtered platelets. Greater than 90% inhibition of platelet aggregation in response to threshold concentrations of adenosine diphosphate (n = 6) and epinephrine (n = 6) was observed in all donors when 0.01 mumol/L iloprost, 0.1 mumol/L PGI2, and 1 mumol/L PGE1 were added to platelet-rich plasma. In gel-filtered platelets, at threshold concentrations of thrombin (n = 6), 90% inhibition was observed with 0.01 mumol/L iloprost. In contrast, similar inhibition to thrombin required 0.1 mumol/L PGI2, and with PGE1 it was never achieved in two donors. At 0.01 mumol/L of prostanoid, cAMP levels (n = 6) rose from a baseline value of 439 +/- 99 pmol/10(9) platelets to 1857 +/- 454 pmol/10(9) platelets for iloprost, 758 +/- 99 pmol/10(9) platelets for PGI2, and 692 +/- 199 pmol/10(9) platelets for PGE1. In addition, at 6 mumol/L, alterations in coronary flow (P greater than 0.05) were noted to be 127% of baseline values for iloprost (n = 5) and 153% for PGI2 (n = 6).(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Diphosphate↗
PubMed1987

Carotid endarterectomy in patients with heparin-induced platelet activation: comparative efficacy of aspirin and iloprost (ZK36374).

Patients with heparin-induced platelet activation who are reexposed to heparin may have recurrent thrombocytopenia, intravascular thrombosis, arterial emboli, or sudden death. To permit carotid endarterectomy in two patients with confirmed heparin-induced platelet activation, we compared the efficacies of aspirin and iloprost, a stable analogue of prostacyclin, in preventing heparin-induced platelet activation. In the first patient, although aspirin prevented both in vitro heparin-induced platelet aggregation (70% without and 7.5% with aspirin) and 14C serotonin release (48% without and 0% with aspirin), intraoperative administration of heparin resulted in an increase in plasma levels of platelet factor 4 from 8 to 260 ng/ml and beta-thromboglobulin levels from 29 to 39 ng/ml. In addition, the circulating platelet count decreased from 221,000 to 174,000 microliters, and 15% spontaneous platelet aggregation was observed. Fortunately, fibrinopeptide A levels remained less than 10 ng/ml intraoperatively, and no thrombotic complications occurred. In the second patient, aspirin did not prevent heparin-induced platelet aggregation in vitro (65% without and 41% with aspirin); however, iloprost (0.01 mumol/L) prevented both in vitro heparin-induced platelet aggregation (59.5% without and 0.0% with iloprost) and 14C serotonin release (56.7% without and 0.0% with iloprost). Therefore, a continuous infusion of iloprost was begun before administration of heparin and was continued until 20 minutes after reversal of heparin with protamine. After intraoperative administration of heparin, plasma levels of platelet factor 4 increased from 19 to 200 ng/ml, and beta-thromboglobulin levels increased from 56 to 76 ng/ml.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗