Aspirin 'resistance': role of pre-existent platelet reactivity and correlation between tests.

BACKGROUND: Aspirin 'resistance' is a widely used term for hyporesponsiveness to aspirin in a platelet function test. Serum thromboxane (TX) B(2) is the most specific test of aspirin's effect on platelets. OBJECTIVES: (i) To examine the role of pre-existent platelet hyperreactivity in aspirin 'resistance'. (ii) To determine the correlation between aspirin resistance defined by serum TXB(2) and other assays of platelet function. METHODS: To enable pre-aspirin samples to be drawn, platelet function was measured in normal subjects (n = 165) before and after aspirin 81 mg daily for seven days. RESULTS: The proportion of the post-aspirin platelet function predicted by the pre-aspirin platelet function was 28.3 +/- 7.5% (mean +/- asymptotic standard error) for serum TXB(2), 39.3 +/- 6.8% for urinary 11-dehydro TXB(2), 4.4 +/- 7.7% for arachidonic acid-induced platelet aggregation, 40.4 +/- 7.1% for adenosine diphosphate-induced platelet aggregation, 26.3 +/- 9.2% for the VerifyNow Aspirin Assay, and 45.0 +/- 10.9% for the TEG PlateletMapping System with arachidonic acid. There was poor agreement between aspirin-resistant subjects identified by serum TXB(2) vs. aspirin-resistant subjects identified by the other five assays, irrespective of whether the analysis was based on categorical or continuous variables. Platelet count correlated with pre-aspirin serum TXB(2) and VerifyNow Aspirin Assay, but not with any post-aspirin platelet function test. CONCLUSIONS: (i) Aspirin 'resistance' (i.e. hyporesponsiveness to aspirin in a laboratory test) is in part unrelated to aspirin but is the result of underlying platelet hyperreactivity prior to the institution of aspirin therapy. (ii) Aspirin resistance defined by serum TXB(2) shows a poor correlation with aspirin resistance defined by other commonly used assays.

The active metabolite of prasugrel inhibits adenosine diphosphate- and collagen-stimulated platelet procoagulant activities.

BACKGROUND: Prasugrel is a novel antiplatelet prodrug of the same thienopyridine class as clopidogrel and ticlopidine. Metabolism of prasugrel generates the active metabolite R-138727, an antagonist of the platelet P2Y(12) adenosine diphosphate (ADP) receptor, leading to inhibition of ADP-mediated platelet activation and aggregation. ADP also enhances the platelet response to collagen, and these two agonists contribute to the generation of platelet procoagulant activity. We therefore examined whether R-138727 inhibits ADP- and collagen-triggered platelet procoagulant activities. METHODS AND RESULTS: As shown by whole blood flow cytometry, R-138727 inhibited surface phosphatidylserine expression on ADP plus collagen-stimulated platelets and tissue factor (TF) expression on ADP-, collagen-, and ADP plus collagen-stimulated monocyte-platelet aggregates. R-138727 reduced monocyte-platelet aggregate formation, thereby further inhibiting TF expression. ADP, collagen, and ADP plus collagen accelerated the kinetics of thrombin generation in recalcified whole blood and R-138727 significantly inhibited this acceleration. Clot strength in a modified thromboelastograph system was also inhibited by R-138727 (IC50 0.7 +/- 0.1 microM). CONCLUSIONS: In addition to its previously known inhibitory effects on platelet activation and aggregation, the active metabolite of prasugrel, R-138727, inhibits platelet procoagulant activity in whole blood (as determined by phosphatidylserine expression on platelets and TF expression on monocyte-platelet aggregates), resulting in the functional consequences of delayed thrombin generation and impaired clot development.

[Gastroesophageal reflux as a cause of vocal dysfunction]. / Disfunción de cuerdas vocales secundaria a reflujo gastroesofágico.

Vocal cord dysfunction (VCD), is characterized by a paradoxical adduction of the vocal cords during inspiration, and occurs predominantly in young women. Common symptoms are cough, wheezing, episodic dyspnea, and inspiratory stridor. The true incidence and course of the disease are unknown, and it is usually self limited. It can coexist with, or mimic refractory asthma. Psychological disorders were thought to be the principal cause, subsequently multiple organic diseases have also been reported, like gastroesophageal reflux disease (GERD). Diagnosis is made by clinical suspicion and direct observation. The Gold standard for diagnosis is laryngoscopy with visualization of the paradoxical motion of the vocal cords when the patient is symptomatic. Speech therapy and psychotherapy have been used extensively without any prospective study. We report two cases of VCD associated with GERD, both with excellent respond to treatment.

Indices of platelet activation and the stability of coronary artery disease.

AIM: To determine whether indices of platelet activation are associated with the stability of coronary artery disease (CAD). METHODS: Platelet function was examined in 677 consecutive aspirin-treated patients presenting for cardiac catheterization. Patients were grouped into recent myocardial infarction (MI), no MI but angiographically documented CAD (non-MI CAD) and no angiographically detectible CAD (no CAD), as well as additional subgroups. RESULTS: Compared with non-MI CAD or no CAD patients, more patients with recent MI had a shortened platelet function analyzer (PFA)-100 collagen-epinephrine closure time (CT) and increased circulating monocyte-platelet aggregates, neutrophil-platelet aggregates, activated platelet surface GPIIb-IIIa and plasma soluble CD40 ligand (sCD40L). More patients with non-MI CAD had shortened PFA-100 CTs and increased monocyte-platelet aggregates compared with patients with no CAD. Platelet surface P-selectin did not differ among the groups. Subgroup analysis revealed that decreasing PFA-100 CT correlated with the stability of CAD. CONCLUSIONS: Indices of platelet activation, especially the PFA-100 CT, are associated with the stability of CAD, and may reflect plaque instability, an ongoing thrombotic state and/or reduced responsiveness to aspirin.

Evidence that pre-existent variability in platelet response to ADP accounts for 'clopidogrel resistance'.

BACKGROUND: Clopidogrel is a widely used antithrombotic agent that inhibits the platelet P2Y(12) adenosine diphosphate (ADP) receptor. There is increasing interest in 'clopidogrel resistance'. OBJECTIVES: To determine whether 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP. METHODS: Platelet response to 20 microm ADP was analyzed by four independent whole blood flow cytometric assays: platelet surface activated GPIIb-IIIa, platelet surface P-selectin, monocyte-platelet aggregates and neutrophil-platelet aggregates. In 25 consecutive, non-aspirin-treated healthy subjects, we studied platelet response before and after clopidogrel administration. In addition, we studied the platelet response in 613 consecutive aspirinated patients with or without coronary artery disease (CAD, as determined by angiography) who had or had not been treated with clopidogrel. In these patients, we tested for homogeneity of variance across all durations of clopidogrel exposure and severity of CAD by estimating the 'goodness of fit' of two independent models. RESULTS: In the healthy subjects, pre-clopidogrel response to ADP predicted post-clopidogrel response to ADP. In the patients, clopidogrel, as expected, inhibited the platelet response to ADP. However, irrespective of the duration of clopidogrel administration, the severity of CAD, and the dose of aspirin, clopidogrel did not increase the variance in the platelet response to ADP in any of the four assays of platelet response. CONCLUSIONS: These studies provide evidence that 'clopidogrel resistance' is accounted for by a pre-existent variability in platelet response to ADP and this variability is not increased by clopidogrel administration.

Effects of platelet binding on whole blood flow cytometry assays of monocyte and neutrophil procoagulant activity.

BACKGROUND: Monocytes and neutrophils form heterotypic aggregates with platelets initially via engagement of platelet surface P-selectin with leukocyte surface P-selectin glycoprotein ligand-1 (PSGL-1). The resultant intracellular signaling causes the leukocyte surface expression of tissue factor and activation of leukocyte surface Mac-1 (integrin alphaMbeta2, CD11b/CD18). The activation-dependent conformational change in monocyte surface Mac-1 results in the binding of coagulation factor Xa (FXa) and/or fibrinogen to Mac-1. The aim of this study was to develop whole blood flow cytometry assays of these procoagulant activities and to investigate the effects of platelet binding to monocytes and neutrophils. METHODS: Citrate or D-Phe-Pro-Arg-chloromethylketone (PPACK) anticoagulated whole blood was incubated with monoclonal antibodies against CD14 (PECy5), CD42a (PE), FITC-conjugated test antibody and an agonist, and then fixed with FACS lyse. Appropriate isotype negative controls were prepared in parallel. A BD FACSCalibur was used to analyze monocytes and neutrophils, which were identified based on CD14 fluorescence, forward and 90 degrees light scatter. These populations were further gated into CD42a-positive (platelet-bound) and CD42a-negative (platelet-free). Geometric mean fluorescence and per cent positive data were collected for each subpopulation to measure the binding of test antibodies directed at CD42a, tissue factor, coagulation FXa, bound fibrinogen, activated Mac-1, and CD11b. Compensation controls were prepared on six normal donors prior to the study and these settings were used throughout the 10 donor study. Negative controls verified the lack of cross talk, particularly in the quantified FITC and PE parameters. RESULTS: The physiologic agonists collagen and ADP increased monocyte-platelet and neutrophil-platelet aggregates and increased leukocyte surface Mac-1/CD11b and surface-bound tissue factor, FXa and fibrinogen. Whereas the increases in Mac-1/CD11b were mainly independent of leukocyte-platelet binding, the increases in surface-bound tissue factor, FXa and fibrinogen were mainly dependent on leukocyte-platelet binding. CONCLUSIONS: (i) We have developed novel whole blood flow cytometry assays to measure bound tissue factor, coagulation FXa, fibrinogen, activated Mac-1 and CD11b on the surface of monocytes and neutrophils, allowing independent analysis of monocytes and neutrophils with and without surface-adherent platelets. (ii) The monocyte and neutrophil surface binding of tissue factor, FXa and fibrinogen is mainly dependent on platelet adherence to monocytes and neutrophils, whereas the monocyte and neutrophil surface expression of CD11b and activated Mac-1 is mainly independent of platelet adherence to monocytes and neutrophils.

Plasma leptin concentration increases early during highly active antiretroviral therapy for acquired immunodeficiency syndrome, independent of body weight.

Leptin, the protein product of the obese gene (ob), is secreted by adipocytes. Circulating leptin levels correlate with fat mass in humans, including individuals infected with HIV. Leptin serves as an adipostatic hormone, a permissive factor for reproduction and a modulator of immune function. Leptin is a cytokine, and has been demonstrated to enhance CD4 cell proliferation and IL-2 secretion from CD4 cells in vitro. The role of leptin in HIV-positive patients treated with highly active antiretroviral therapy (HAART) has not been well defined. We haveevaluated leptin levels in HIV-infected individualsduringthe early phase of HAART. We measured plasma leptin levels in 15 antiretroviral-naive HIV positive patients at baseline and after 1 and 4 weeks of HAART. After the first week of therapy, mean leptin level and CD4 count were increased compared to baseline, 6.0 vs 7.2 ng/ml (p = 0.004) and 377 vs 432 cells/ul (p = 0.014), respectively. In contrast, mean body mass index (BMI) remained unchanged 27.0 vs 26.8 kg/m2 (p < 0.08). After four weeks of therapy, leptin and BMI values were unchanged compared to baseline, 6.0 vs 5.9 (p < 0.4) and 27.0 vs 26.9 (p < 0.5), respectively, whereas CD4 count continued to increase to 491 cells/ul (p < 0.012 compared to baseline). These data demonstrate an early transient increase in plasma leptin levels in HIV positive patients initiated on HAART, despite a lack of change in BMI. It is unclear if the transient increase in leptin is related to its role as a cytokine, a metabolic regulator, or reproductive factor.

GPIIb-IIIa antagonists reduce thromboinflammatory processes in patients with acute coronary syndromes undergoing percutaneous coronary intervention.

OBJECTIVE: To investigate the effects of abciximab, eptifibatide and no GPIIb-IIIa antagonist (control) on soluble CD40 ligand (sCD40L) and the formation of leukocyte-platelet aggregates (LPA) in 98 ACS patients undergoing percutaneous coronary intervention (PCI). BACKGROUND: sCD40L and LPA are increased in patients with ACS. METHODS: sCD40L was measured by enzyme-linked immunosorbent assay (ELISA) and LPA by whole blood flow cytometry. RESULTS: There were no baseline differences between the three groups in sCD40L and LPA. At the end of PCI, sCD40L was unchanged in the controls, decreased by 30% (P < 0.001) in the abciximab group and by 11% (P < 0.02) in the eptifibatide group. Eighteen to 24 h after PCI, sCD40L was unchanged in the controls, reduced 30% (P < 0.001) in the abciximab-treated group and 9% (P < 0.01) in the eptifibatide-treated group. At the end of PCI, circulating monocyte-platelet aggregates (MPA) were reduced by 12% (P = NS) in the abciximab-treated group, 13% in the eptifibatide-treated group (P = NS), but slightly increased in the controls (P = NS). Eighteen to 24 h after PCI, MPA were reduced by 41% (P < 0.001) compared to baseline in the abciximab-treated group, by 23% (P = NS) in the eptifibatide-treated group, and 15% (P = NS) in the controls. In contrast to control patients presenting while on clopidogrel, control patients presenting not on clopidogrel demonstrated a reduction in sCD40L and LPA 18-24 h post-PCI (P = NS). At low receptor occupancy, GPIIb-IIIa antagonists did not augment the release of sCD40L or the number of circulating LPA. CONCLUSIONS: GPIIb-IIIa antagonists reduce circulating sCD40L and LPA formation in patients with ACS undergoing PCI. At low receptor occupancy, GPIIb-IIIa antagonists do not activate platelets.

Leukocyte-platelet aggregation, platelet surface P-selectin, and platelet surface glycoprotein IIIa after percutaneous coronary intervention: Effects of dalteparin or unfractionated heparin in combination with abciximab.

BACKGROUND: Plaque disruption with resultant platelet activation and leukocyte-platelet aggregation is a pathophysiologic process common to both acute coronary syndromes and percutaneous coronary interventions. Unfractionated heparin is a standard antithrombotic therapy in patients with both acute coronary syndromes and in those undergoing percutaneous coronary interventions. Low-molecular-weight heparins have been reported to cause less platelet activation than unfractionated heparin. METHODS: Monocyte-platelet aggregates, neutrophil-platelet aggregates, platelet surface P-selectin, and platelet surface glycoprotein (GP) IIIa were measured serially by whole blood flow cytometry in 40 patients with unstable angina (randomly assigned to either unfractionated heparin 70 U/kg or the low-molecular-weight heparin dalteparin 60 IU/kg) undergoing coronary intervention with planned abciximab administration (in 2, one-half-dose boluses). Assays were performed at baseline, 5 minutes after administration of either type of heparin, 10 minutes after the first bolus of abciximab, 10 minutes after second bolus of abciximab, and 8 to 10 and 16 to 24 hours after administration of either heparin. RESULTS: No significant differences in clinical outcomes were observed between patients receiving either unfractionated heparin or dalteparin. The number of circulating P-selectin-positive platelets was increased by unfractionated heparin but not dalteparin, and abciximab reversed this increase. The number of circulating P-selectin-positive platelets was reduced below baseline levels in both treatment groups 8 to 10 and 16 to 24 hours after study drug administration. At 8 to 10 and 16 to 24 hours after administration of study drug, platelet degranulation in response to iso-thrombin receptor agonist peptide 1.5 mmol/L was significantly reduced by almost 50% (compared with immediately after study drug administration). Both unfractionated heparin and dalteparin significantly increased the numbers of circulating monocyte-platelet and neutrophil-platelet aggregates, which were subsequently reduced to baseline levels after administration of the second abciximab bolus and to below baseline at both 8 to 10 and 16 to 24 hours in all patients. After both unfractionated heparin and dalteparin administration, platelet surface GP IIIa expression was significantly increased compared with baseline at both 8 to 10 and 16 to 24 hours. CONCLUSIONS: Dalteparin in combination with abciximab in patients with unstable angina undergoing coronary intervention appears to be safe. Unfractionated heparin, but not dalteparin, degranulates platelets in patients with unstable angina. Both heparins increase the number of circulating monocyte-platelet and neutrophil-platelet aggregates. Abciximab therapy during coronary interventions rapidly reduces the number of degranulated platelets and leukocyte-platelet aggregates.

Explaining employees' health care costs: a prospective examination of stressful job demands, personal control, and physiological reactivity.

The authors tested the ability of stressful demands and personal control in the workplace to predict employees' subsequent health care costs in a sample of 105 full-time nurses. Both subjective and objective measures of workload demands interacted with personal control perceptions in predicting the cumulative health care costs over the ensuing 5-year period. Tonic elevations in salivary cortisol, moreover, mediated the effects of demands and control on health care costs. Neither the job demands variables nor physiological reactivity measures, however, explained subsequent mental health. The results support findings from the epidemiological literature that demonstrate an important role for employees' control in explaining occupational inequalities in coronary heart disease and mortality. The authors argue that the results also encourage control-enhancing job design interventions by suggesting that their outcomes can benefit both organizations and their members.

Circulating monocyte-platelet aggregates are an early marker of acute myocardial infarction.

OBJECTIVES: We investigated whether elevated levels of circulating monocyte-platelet aggregates (MPA) can be used to identify patients with acute myocardial infarction (AMI). BACKGROUND: Commonly used blood markers of AMI reflect myocardial cell death, but do not reflect the earlier pathophysiologic processes of plaque rupture, platelet activation and resultant thrombus formation. Circulating MPA form after platelet activation. METHODS: In a single center between October 1998 and November 1999, we measured circulating MPA in a blinded fashion by whole blood flow cytometry in 211 consecutive patients who presented to the emergency department (ED) with chest pain and were admitted to rule out AMI. Acute myocardial infarction was diagnosed by a CK-MB fraction greater than three times control. RESULTS: Patients with AMI (n = 61), as compared with those without AMI (n = 150), had significantly higher numbers of circulating MPA (11.6 +/- 11.4 vs. 6.4 +/- 3.6, mean +/- SD, p < 0.0001). After controlling for age, the adjusted odds of developing AMI for patients in the 2nd, 3rd and 4th quartiles of MPA, in comparison with patients in the lowest quartile (odds ratio = 1.0), were 2.1 (95% confidence interval [CI]: 0.7, 6.8), 4.4 (95% CI: 1.5, 13.1) and 10.8 (95% CI: 3.6, 32.0), respectively. The number of circulating MPA in patients with AMI presenting within 4 h of symptom onset (14.4) was significantly greater than those presenting after 4 h (9.4) and after 8 h (7.0), (p < 0.001). Of the 61 patients with AMI, 35 (57%) had a normal creatine kinase isoenzyme ratio at the time of presentation to the ED, but had high levels of circulating MPA (13.3). CONCLUSIONS: Circulating MPA are an early marker of AMI.

Validation of an outcome scale for use in adult psychiatric practice.

OBJECTIVE: To clarify the usefulness, acceptability, sensitivity, and validity of version 4 of the Health of the Nation Outcome Scale (HoNOS), a scale developed to meet the requirement for a clinically acceptable outcome scale for routine use in mental illness services. DESIGN: Patients with a range of mental illnesses were rated on the HoNOS at the beginning and end of an episode by interviews with mental health professionals. SUBJECTS: 934 patients from eight diagnostic categories were rated by 129 mental health professionals at 17 sites; 250 were also rated on a range of comparison scales. OUTCOME MEASURES: Comparison of patients' scores at the beginning and end of an episode using individual item scores, dimensional subscores, and the total score. RESULTS: HoNOS scores decreased by almost 50% between the beginning and end of episodes. They varied with the severity of the setting and discriminant analysis showed that the HoNOS had a moderate level of discriminatory power. Correlation analysis showed acceptable levels of agreement with independent scales, although the accuracy of ratings of some items at the beginning of an episode was affected by information deficits. CONCLUSION: The findings indicate that HoNOS is sensitive to change across time and to differences in illness type and severity, and has a sufficient degree of both construct and criterion related validity to fulfil the requirements of a mental health outcome scale for routine use in clinical settings.

Resistance to multiple fluoroquinolones in a clinical isolate of Streptococcus pyogenes: identification of gyrA and parC and specification of point mutations associated with resistance.

A strain of Streptococcus pyogenes resistant to multiple fluoroquinolones was isolated from the blood of an immunocompromised patient. Resistance to fluoroquinolones in S. pyogenes has not been previously studied. Compared to 10 sensitive strains of S. pyogenes, the fluoroquinolone-resistant clinical isolate of S. pyogenes presented point mutations in gyrA, predicting that serine-81 was changed to phenylalanine and that methionine-99 was changed to leucine, and in parC, predicting that serine-79 was changed to tyrosine. The mechanism of fluoroquinolone resistance in this isolate of S. pyogenes appears to be analogous to previously reported mechanisms for Streptococcus pneumoniae.

Reducing stress by increasing control.

The concept of having control over your work has long been viewed as an essential part of human motivation and is linked with the idea that individuals seek to master their environments and to be effective in producing change. Over the past decade, the notion of control also has become an important factor in helping to alleviate job-related stress. Considerable evidence exists to suggest that workers actually might have improved physical and mental health and be more productive under stressful conditions if they possess the requisite level of control.

An investigation of the effects of time and involvement in the relationship between stressors and work-family conflict.

Previous researchers have proposed that the time and energy involved in family and paid work should affect the relationship between stressors and conflict in both the work and family domains. Using a sample of 113 registered nurses, the authors hypothesized that the amount of time and involvement in both domains would moderate the stressor-conflict relationships. Results supported many of the interactions in predicting conflict in each domain, and implications for the health of working women with family responsibilities were discussed.

Modulation of NK cell cytolytic activity by macrophages in chronically exercise-stressed mice.

This study was designed to investigate the effects of moderate-intensity endurance training on basal natural killer (NK) cell cytolytic activity in murine splenocytes that were enriched for 1) NK1.1+ cells or 2) macrophages and NK1.1+ cells. Mice were assigned to sedentary (Sed), treadmill control (TM), or treadmill-trained (Trn) groups. Splenocyte number, the percentages of NK1.1+, large granular lymphocytes (NK1.1+, LGL-1+), and other subpopulations did not change in Trn mice. Approximately 70% of cells enriched for NK1.1+ expressed this surface antigen. Lytic units (LU) expressed per LGL-1+ cell were significantly lower in Trn [83.9 +/- 3.2 (SE)] compared with Sed (109.5 +/- 7.5) and TM (101.3 +/- 6.4) groups. When macrophages remained in the in vitro assay, LU per LGL-1(+) cell did not differ across groups. The results indicate that highly enriched NK1.1+ cells from Trn mice had lower NK cell activity compared with Sed mice. No differences in NK cell activity were observed when cells were enriched for NK1.1+ cells and macrophages. These findings support the hypothesis that macrophage modulation of NK cells may be one mechanism contributing to augmented basal NK cell activity in endurance-trained individuals.

The influence of cardiopulmonary bypass on ionized magnesium in neonates, infants, and children undergoing repair of congenital heart lesions.

The purpose of this study was to measure the ionized magnesium (iMg) concentrations in children undergoing the correction of congenital heart defects. iMg levels were measured in 115 consecutive patients at five sample periods: prebypass, onset of bypass, during rewarming, immediately postbypass, and 1 h postbypass using an ion-selective electrode of the NOVA-CRT 8 (Nova Biomedical, Watham, MA). The incidence of dysrythmias was noted. Patients were divided into two groups: those who received Plegisol as the cardioplegic solution and those who did not. This study demonstrates that iMg decreases with the onset of cardiopulmonary bypass (CPB) in patients who weigh < 10 kg. In the Plegisol group, all subgroups of patients demonstrated statistically higher iMg during the rewarming phase of CPB, immediately post-CPB, and 1 h post-CPB, when compared with control values. The probability of dysrhythmias in the Plegisol group was almost twice that of the non-Plegisol group. However, this did not reach statistical significance (P = 0.22). The results of our study demonstrate that the use of CPB on pediatric patients produces alterations in the iMg. The changes differ depending on both patient weight and the use of a magnesium-containing cardioplegic solution, exemplified here by Plegisol. The role of these changes in iMg on dysrhythmias could not be further evaluated.

Transcatheter closure of ventricular septal defects: hemodynamic instability and anesthetic management.

The technique of transcatheter ventricular septal defect (VSD) device closure may be associated with significant hemodynamic instability. The anesthetic records and catheterization data of 70 consecutive transcatheter VSD closures between February 1989 and September 1992 were reviewed, and risk factors associated with hemodynamic instability evaluated. In 28 of 70 procedures (40%), hypotension (> 20% decrease in systolic blood pressure from baseline) occurred; 12 responded to administration of fluids intravascularly alone, whereas 16 patients required additional acute resuscitation. Significant dysrhythmias occurred during 20 (28.5%) anesthetics associated with hypotension and requiring treatment or catheter withdrawal. ASA physical status, precatheterization indication for device placement, and patient size were not predictive of hemodynamic instability during the procedure. Blood transfusions were necessary in 38 (54.4%) cases and were size-related, with patients weighing less than 10 kg requiring a significantly larger transfusion volume (25.1 +/- 12.4 mL/kg). After 35 procedures (50%) patients were admitted directly to the intensive care unit (ICU) due primarily to hemodynamic instability or procedure duration; 24 (68%) required mechanical ventilation. No deaths occurred; there was no late morbidity due to catheterization-related events. Intravenous sedation was used for the initial catheterizations, maintained with a combination of midazolam, ketamine, and morphine. Subsequently general intravenous or inhaled anesthesia was predominantly used during transesophageal echocardiography and internal jugular vein cannulation. We conclude that hemodynamic instability is common during device closure of VSDs, and is likely to be an inescapable feature of these procedures in many patients because of the technique necessary for device placement.