Clinical outcomes associated with proton pump inhibitor use among clopidogrel-treated patients within CYP2C19 genotype groups following acute myocardial infarction.

We examined clinical outcomes with proton pump inhibitors (PPI) use within CYP2C19 genotype groups during clopidogrel treatment following acute myocardial infarction (AMI). 2062 patients were genotyped for CYP2C19*2 and *17 variants in TRIUMPH. 12 month clinical outcomes were analyzed among patients discharged on clopidogrel within CYP2C19*2 carrier, CYP2C19*17 carrier, and CYP2C19*1 homozygote genotype groups. PPI use was not associated with a difference in mortality. Among clopidogrel-treated Caucasians following AMI, PPI use was associated with a significantly higher rate of cardiac rehospitalization (HR 1.62, 95% CI 1.19-2.19; P=0.002) compared with no PPI use. PPI users who were carriers of the CYP2C19*17 variant experienced significantly higher rates of cardiac rehospitalization (HR 2.05, 95% CI 1.26-3.33; P=0.003), carriers of the CYP2C19*2 variant had a trend toward increased 1-year cardiac rehospitalization (HR 1.69, 95% CI 0.95-2.99; P=0.07), while no significant differences were observed among CYP2C19*1 homozygotes. These results indicate that the risks associated with PPI use among clopidogrel-treated Caucasian post-MI patients are impacted by CYP2C19 genotype, and suggest knowledge of genotype may be useful for personalizing PPI use among patients following AMI to reduce rehospitalization.

Identification of a 36,000-molecular weight, gag-related phosphoprotein in lymphoma cells transformed by radiation leukemia virus.

Radiation leukemia virus (RadLV) causes thymic lymphoma in 90% of susceptible mice after a latent period of several months. The virally encoded polypeptides produced by RadLV-induced lymphoma cells were analyzed by immunoprecipitation and NaDodSO4/polyacrylamide gel electrophoresis. Along with the expected precursor and mature forms of gag and env gene products, a polypeptide of 36,000 molecular weight (p36) was precipitated by anti-gag antisera. It was not precipitable by normal sera or anti-env antibodies. Like the gag-associated fusion proteins of some acute leukemia viruses, p36 was found to be phosphorylated in vivo, although it lacked detectable ATP-specific protein kinase activity in vitro. By kinetics during pulse-chase labeling experiments and by comparison of two-dimensional tryptic peptide maps, this protein is not an intermediate in gag precursor processing. One lymphoma cell line is described that resembles a nonproducer RadLV-transformant, synthesizing relatively large amounts of p36 in the absence of Pr66gag or p30 production. Several RadLV-induced lymphoma cell lines also produce p36, while it was not detectable in the radiation-induced lines tested. In addition, p36 was not produced by mouse or mink fibroblasts or cultured thymocyte cell lines infected with virus passaged from the RadLV-induced lymphomas. We conclude that p36 may represent a previously unrecognized transformation-related protein induced directly or indirectly by infection with RadLV.

Predictors of mortality and mortality from cardiac causes in the bypass angioplasty revascularization investigation (BARI) randomized trial and registry. For the BARI Investigators.

BACKGROUND: The impact of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG) on long-term mortality rates in the presence of various demographic, clinical, and angiographic factors is uncertain in the population of patients suitable for both procedures. METHODS AND RESULTS: In the Bypass Angioplasty Revascularization Investigation (BARI) randomized trial and registry, 3610 patients who were eligible to receive PTCA and CABG were revascularized between 1989 and 1992. Multivariate Cox models were used to identify factors associated with 5-year mortality and cardiac mortality, with particular attention to factors that interact with treatment. Diabetic patients receiving insulin had higher mortality and cardiac mortality rates with PTCA compared with CABG (relative risk [RR] 1.78 and 2.63, respectively, P<0.001), and patients with ST elevation had higher cardiac mortality rates with CABG than with PTCA (RR 4.08, P<0.001). Factors most strongly associated with high overall mortality rates were insulin-treated diabetes, congestive heart failure, kidney failure, and older age. Black race was also associated with higher mortality rates (RR 1.49, P=0.019). CONCLUSIONS: A set of variables was identified that could be used to help select a revascularization procedure and to evaluate risk of long-term mortality in the population of patients considering revascularization.

Assessing the hemodynamic significance of coronary artery stenoses: analysis of translesional pressure-flow velocity relations in patients.

OBJECTIVES: The purpose of this study was to examine the relation among the angiographic severity of coronary artery lesions, coronary flow velocity and translesional pressure gradients. BACKGROUND: Determination of the clinical and hemodynamic significance of coronary artery stenoses is often difficult and inexact. Angiography has been shown to be an imperfect tool for determining the physiologic significance of eccentric or irregular coronary lumen narrowing. METHODS: Using a 0.018-in. (0.046 cm) intracoronary Doppler-tipped angioplasty guide wire, spectral flow velocity data both proximal and distal to coronary stenoses were compared with translesional pressure gradient measurements and angiographic data obtained during cardiac catheterization in 101 patients. There were 17 patients with normal angiographic findings and 84 with coronary artery disease, with lesions ranging from 28% to 99% diameter narrowing. Patients with coronary disease were assigned to two groups on the basis of translesional gradients at rest. Group A (n = 56) had gradients < 20 mm Hg, and Group B (n = 28) had gradients > or = 20 mm Hg. RESULTS: Proximal average peak velocity, diastolic velocity integral and total velocity integral were slightly but statistically lower in Group A; however, the distal average peak velocity and diastolic and total velocity integrals were all markedly (all p < 0.01) decreased in patients with gradients > or = 20 mm Hg (Group B). In addition, the ratio of proximal to distal total flow velocity integral was higher in Group B (2.4 +/- 1.0) than in group A (1.1 +/- 0.3, p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal to distal total flow velocity integrals (r = 0.8, p < 0.001), with a weaker relation between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). In angiographically intermediate stenoses (range 50% to 70%), angiography was a poor predictor of translesional gradients (r = 0.2, p = NS), whereas the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.001). Only two patients with a proximal/distal total flow velocity ratio < 1.7 had a translesional gradient > 30 mm Hg. Both patients had a very proximal lesion in a nonbranching right coronary artery. CONCLUSIONS: These data demonstrate that in branching human coronary arteries, a close relation exists between translesional hemodynamics and distal coronary flow velocity. Translesional coronary flow velocity is a new and easily applicable method for determining the hemodynamic significance of coronary artery stenoses that is superior to angiography and can be applied at the time of diagnostic catheterization. These data will provide a rational approach to making decisions on the use of coronary interventional techniques when angiographic findings are questionable.

Variations in normal coronary vasodilatory reserve stratified by artery, gender, heart transplantation and coronary artery disease.

OBJECTIVES: The purpose of the study was to assess the spectrum of coronary vasodilatory reserve values in patients with angiographically normal arteries who had atypical chest pain syndromes or remote coronary artery disease or were heart transplant recipients. BACKGROUND: The measurement of post-stenotic coronary vasodilatory reserve, now possible in a large number of patients in the cardiac catheterization laboratory, is increasingly used for decision making. Controversy exists regarding the range of normal values obtained in angiographically normal coronary arteries in patients with different clinical presentations. METHODS: Quantitative coronary arteriography was performed in 214 patients classified into three groups: 85 patients with chest pain syndromes and angiographically normal arteries (group 1); 21 patients with one normal vessel and at least one vessel with > 50% diameter lumen narrowing (group 2); and 108 heart transplant recipients (group 3). Coronary vasodilatory reserve (the ratio of maximal to basal average coronary flow velocity) was measured in 416 arteries using a 0.018-in. (0.04 cm) Doppler-tipped angioplasty guide wire. Intracoronary adenosine (8 to 18 micrograms) was used to produce maximal hyperemia. RESULTS: Coronary vasodilatory reserve was higher in angiographically normal arteries in patients with chest pain syndromes (group 1:2.80 +/- 0.6 [group mean +/- SD]) than in normal vessels in patients with remote coronary artery disease (group 2: 2.5 +/- 0.95, p = 0.04); both values were significantly higher than those in the post-stenotic segment of the diseased artery (1.8 +/- 0.6, p < 0.007). Coronary vasodilatory reserve in transplant recipients (group 3) was higher than that in the other groups (3.1 +/- 0.9, p < 0.05 vs. groups 1 and 2) as a group and for individual arteries. When stratified by vessel, coronary vasodilatory reserve was similar among the left anterior descending, left circumflex and right coronary arteries. There were no differences between coronary vasodilatory reserve values on the basis of gender for patients with coronary artery disease and transplant recipients. In group 1 (chest pain), there was a trend toward higher coronary vasodilatory reserve in men than in women (2.9 +/- 0.6 vs 2.7 +/- 0.6, p = 0.07). CONCLUSIONS: These findings identify a normal reference range for studies assessing the coronary circulation and post-stenotic coronary vasodilatory reserve in patients with and without coronary artery disease encountered in the cardiac catheterization laboratory.

Clinical outcome of deferring angioplasty in patients with normal translesional pressure-flow velocity measurements.

OBJECTIVES: The objective of this study was to determine the feasibility, safety and outcome of deferring angioplasty in patients with angiographically intermediate lesions that are found not to limit flow, as determined by direct translesional hemodynamic assessment. BACKGROUND: The clinical importance of some coronary stenoses of intermediate angiographic severity frequently requires noninvasive stress testing. Direct translesional pressure and flow measurements may assist in clinical decision making in patients with such stenoses. METHODS: Translesional spectral flow velocity (Doppler guide wire) and pressure data were obtained in 88 patients for 100 lesions (26 single-vessel and 74 multivessel coronary artery lesions) with quantitative angiographic coronary narrowings (mean +/- SD diameter narrowing 54 +/- 7% [range 40% to 74%]). Target lesion angioplasty was prospectively deferred on the basis of predetermined normal values, defined as a proximal/distal velocity ratio < 1.7 or a pressure gradient < 25 mm Hg, or both. Patients were followed up for 9 +/- 5 months (range 6 to 30). RESULTS: In the deferred angioplasty group, translesional velocity ratios were similar to those of a normal reference group (mean 1.1 +/- 0.32 vs. 1.3 +/- 0.55) and significantly lower than those of a reference cohort of patients who had undergone angioplasty (2.27 +/- 1.2, p < 0.05). The mean translesional pressure gradient in the deferred angioplasty group was also lower than that in the angioplasty group (10 +/- 9 vs. 45 +/- 22 mm Hg, p < 0.001). At follow-up in the deferred angioplasty group, four, six, zero and two patients, respectively, had had subsequent angioplasty, coronary artery bypass graft surgery or myocardial infarction or had died. In one patient, death was related to angioplasty of a nontarget artery lesion, and one patient with multivessel disease had a cardiac arrest due to ventricular fibrillation 12 months after lesion assessment. Among the 10 patients requiring later angioplasty or coronary artery bypass grafting, only six procedures were performed on target arteries. No patient had a complication of translesional flow or pressure measurements. CONCLUSIONS: These data demonstrate the safety, feasibility and clinical outcome of deferring angioplasty of coronary artery narrowings associated with normal translesional coronary hemodynamic variables. Given the practice of performing angioplasty without ischemic testing or when testing is inconclusive, translesional hemodynamic data obtained at diagnostic catheterization can identify patients in whom it is safe to postpone angioplasty.

Role of coronary artery lumen enlargement in improving coronary blood flow after balloon angioplasty and stenting: a combined intravascular ultrasound Doppler flow and imaging study.

OBJECTIVES: This study sought to examine the mechanism of increasing coronary flow reserve after balloon angioplasty and stenting. BACKGROUND: Coronary vasodilatory reserve (CVR) does not improve after percutaneous transluminal coronary angioplasty in > or = 50% of patients, postulated to be due to impaired microvascular circulation or inadequate lumen expansion despite adequate angiographic results. METHODS: To demonstrate the role of coronary lumen expansion, serial coronary flow velocity (0.014-in. Doppler guide wire) was measured in 42 patients before and after balloon angioplasty and again after stent placement. A subset (n = 17) also underwent intravascular ultrasound (IVUS) imaging of the target sites after angioplasty and stenting. CVR (velocity) was computed as the ratio of adenosine-induced maximal hyperemic to basal average peak velocity. RESULTS: The percent diameter stenosis decreased from (mean +/- SD) 84 +/- 13% to 37 +/- 18% after angioplasty and to 8 +/- 8% after stenting (both p < 0.05). CVR was minimally changed from 1.70 +/- 0.79 at baseline to 1.89 +/- 0.56 (p = NS) after angioplasty but increased to 2.49 +/- 0.68 after stent placement (p < 0.01 vs. before and after angioplasty). IVUS lumen cross-sectional area was significantly larger after stenting than after angioplasty (8.39 +/- 2.09 vs. 5.10 +/- 2.03 mm2, p < 0.05). Anatomic variables were related to increasing coronary flow velocity reserve (CVR vs. IVUS lumen area: r = 0.47, p < 0.005; CVR vs. quantitative coronary angiographic percent area stenosis: r = 0.58, p < 0.0001). CONCLUSIONS: In most cases, increases in CVR were associated with increases in coronary lumen cross-sectional area. These data suggest that impaired CVR after angioplasty is often related to the degree of residual narrowing, which at times may not be appreciated by angiography. A physiologically complemented approach to balloon angioplasty may improve procedural outcome.

Interleukin-2 receptor-specific fusion toxin inhibits barotrauma-induced arterial atherosclerosis.

Immunocytochemical analyses of human plaques and experimental arterial lesions have implicated activated lymphocytes and monocytes in the pathogenesis of atherosclerosis, as demonstrated by the expression of interleukin-2 (IL-2) membrane receptors and major histocompatibility complex class II epitopes. The objective is to determine if targeting these cells with an IL-2 receptor-specific chimeric toxin, DAB486-IL-2, can inhibit experimental post-angioplasty vascular neointimal thickening. Twenty-two atherogenically modeled rabbits were treated in vivo with DAB486-IL-2 (0.1 mg/kg per day i.v.; n = 11) or placebo (n = 11) for 10 days following aortic balloon angioplasty (4 atm x 30 s each x 2 dilatations). In vitro 3H-leucine incorporation studies of mononuclear leukocyte and vascular smooth muscle cell protein synthesis inhibition by DAB486-IL-2 were also performed. Angioplasty sites were examined for evidence of hyperproliferative atherosclerotic narrowing by quantitative angiography and histomorphometry of neointimal cross-sectional area at baseline and 6 weeks after injury. In vitro Concanavalin-A stimulated rabbit mononuclear leukocyte protein synthesis was 50% inhibited by DAB486-IL-2 at a concentration (IC50) of 6 x 10(-11) M. Rabbit vascular smooth muscle cells were approximately 150-fold less sensitive to DAB486-IL-2 (IC50 = 10(-8) M). In vivo studies showed no change in angioplasty site angiographic minimum luminal diameter at 6 weeks in DAB486-IL-2 treated animals (from 2.96 +/- 0.52 to 2.96 +/- 0.48 mm; percent cross-sectional area reduction = 1 +/- 10%; P = N.S.). In control animals, luminal diameter decreased from 2.79 +/- 0.4 to 2.32 +/- 0.52 mm at 6 weeks, and percent cross-sectional area was reduced by 34 +/- 14% (P < 0.01 vs. placebo). Quantitative histomorphometric angioplasty segmental intimal cross-sectional area reduction of treated and placebo vessels also differed significantly (19 +/- 16% vs. 31 +/- 21%; P < 0.05). DAB486-IL-2 caused no adverse effects on animal survival, weight or hepatic transaminase levels. We conclude that post-angioplasty administration of the chimeric toxin DAB486-IL-2 inhibits angiographic narrowing and neointimal thickening in the atherogenic rabbit model. Although this IL-2 receptor-specific molecule was cytotoxic in vitro for activated mononuclear leukocytes and vascular smooth muscle cells, systemic toxicity did not occur in vivo at a dose comparable to that evaluated in clinical trials of this agent. Potential anti-proliferative effects of this chimeric toxin may be mediated by direct local inhibition of leukocyte-mediated inflammation, or through the indirect modification of vascular cell mitogenesis and cytokine release.

Effects of percutaneous transluminal coronary angioplasty balloon compliance on angiographic and clinical outcomes.

The effect of balloon compliance on the safety and outcome of percutaneous transluminal coronary angioplasty (PTCA) is controversial. It has been proposed that PTCA balloons constructed from compliant polymers contribute to an increased risk of angiographic coronary dissection and potentially to adverse clinical results. To determine the effect of balloon material compliance on PTCA outcome, 1,076 PTCA procedures using balloons differing in compliance characteristics (polyethylene teraphthalate [noncompliant], polyethylene [intermediately compliant] or polyolefincopolymer [compliant]) were retrospectively analyzed. Baseline clinical, angiographic and procedural variables were similar among the 3 balloon material groups. In the noncompliant, intermediately compliant and compliant groups, the occurrence rates of intimal tears (10, 14 and 10%, respectively; p = NS for all comparisons) and coronary dissection (7, 9 and 8%, respectively; all p = NS) were also equivalent. The rates of acute occlusion, myocardial infarction, emergency bypass surgery and death were low and similar, and likewise unaffected by balloon material. The results provide evidence that the occurrence of adverse outcomes after PTCA is unrelated to balloon material compliance and support the clinical safety of balloons constructed of compliant or noncompliant polymers when used for appropriate coronary interventions.

Comparison of quantitative angiographically derived and measured translesion pressure and flow velocity in coronary artery disease.

Although quantitative coronary angiography (QCA) has been used to determine lesion severity, angiographically derived parameters of translesional physiology have not been compared with those directly measured in the same patients. Thus, the aim of this study was to correlate QCA-derived translesional pressure and flow data with directly measured data in patients. QCA (DCI-ACA program), translesional pressure gradient (2.2Fr fluid-filled tracking catheter), and intracoronary Doppler flow velocity (0.018-inch FloWire) measurements were simultaneously performed in 28 arteries (25 patients). Mean diameter stenosis was 51 +/- 2.3% (range 29 to 73). No patient had left ventricular hypertrophy or valvular heart disease. The arteries studied were left anterior descending in 14, circumflex in 8, and right coronary in 6 patients. Stenotic flow reserve and baseline and maximal gradients were calculated by the DCI program. Coronary flow reserve and baseline and maximal hyperemic gradients were also directly measured distal to the stenosis after administration of intracoronary adenosine (12 to 18 micrograms). QCA-derived pressure gradients did not correlate with the measured gradients at baseline (r2 = 0.005; p = 0.73) or at maximal hyperemia (r2 = 0.1; p = 0.13). No correlation was found between the QCA-predicted flow reserve and the coronary flow reserve measured distal to the stenosis (r2 = 0.02; p = 0.46). Furthermore, stenotic flow reserve and measured gradient were not significantly correlated (r2 = 0.1; p = 0.16). In this range of stenoses of intermediate severity, there was no correlation between the measured pressure gradient or coronary flow reserve and lesion diameter or cross-sectional area by QCA.(ABSTRACT TRUNCATED AT 400 WORDS)

Assessment of angiographically intermediate coronary artery stenosis using the Doppler flowire.

Determination of the clinical and hemodynamic significance of coronary stenoses is often difficult and inexact. Angiography and coronary vasodilator reserve have been shown to be imperfect tools to determine the physiologic significance of coronary stenoses. Spectral flow velocity data, both proximal and distal to coronary stenoses, using an 0.018-in intracoronary Doppler-tipped angioplasty guidewire, were compared to translesional pressure gradients and angiography during cardiac catheterization. Patients were divided into 2 groups based on resting translesional gradients: Group 1 had gradients < 20 mm Hg and group 2 had gradients > or = 20 mm Hg. Proximal average peak velocity, diastolic velocity integral, and total velocity integral were statistically significantly lower in Group 1. The distal average peak velocity, and diastolic and total velocity integrals were all significantly (p < 0.01) decreased in patients with gradients > 20 mm Hg (group 2). The ratio of proximal-to-distal total flow velocity integral was also higher in group 2 patients (2.3 +/- 0.9) compared with group 1 (1.1 +/- 0.2; p < 0.001). There was a strong correlation between translesional pressure gradients and the ratios of the proximal-to-distal total flow velocity integrals (r = 0.8, p < 0.001) with a weaker relationship between quantitative angiography and pressure gradients (r = 0.6, p < 0.001). Angiography was a poor predictor of translesional gradients in angiographically intermediate stenoses (range 50-70%; r = 0.2, p = NS), while the flow velocity ratios continued to have a strong correlation (r = 0.8, p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Quantitating coronary collateral flow velocity in patients during coronary angioplasty using a Doppler guidewire.

Quantitation of coronary collateral flow in patients has been limited to angiographic techniques, which are subject to well-known methodologic limitations. The use of a Doppler-tipped angioplasty guidewire permits measurement of both antegrade and retrograde flow distal to totally or subtotally occluded vessels that may be supplied with acutely recruitable or angiographically mature collateral conduits. Using coronary flow velocity as an indicator of collateral flow, retrograde flow velocity was quantitated in 17 patients. Mean collateral flow velocity was approximately 30% of normal postangioplasty antegrade flow velocity. The phasic pattern of collateral flow was highly variable, but the retrograde diastolic and systolic flow velocity integrals were 20% and 40% (respectively) of post-procedure antegrade flow velocity. Preliminary studies with pharmacologic stimulation of the contralateral supply artery suggests that collateral flow is not increased by intracoronary nitroglycerin (200 micrograms) or adenosine (12 micrograms), but may be markedly augmented during mechanical stimulation of balloon occlusion. These data represent the first in a series of quantitative observations on control of the coronary collateral circulation in humans. Future investigations using the Doppler Flowire (Cardiometrics) will enhance understanding of factors modulating ischemia through collateral supply.

Correlation of poststenotic hyperemic coronary flow velocity and pressure with abnormal stress myocardial perfusion imaging in coronary artery disease.

The functional significance of coronary stenoses is frequently determined by adjunctive noninvasive myocardial perfusion imaging. Poststenotic coronary flow velocity and pressure can be measured directly during routine cardiac catheterization. The aim of this study was to correlate poststenotic (distal) flow velocity and pressure with stress perfusion imaging in patients. Quantitative angiography, basal and hyperemic transstenotic coronary flow velocities, and pressure gradients were measured in 50 patients within 1 week of exercise (n = 29) or of pharmacologic (n = 21) stress perfusion imaging. Twenty-two of 25 patients (88%) with reversible perfusion abnormalities had diminished distal coronary flow velocity reserves (CFVR) of < or = 2.0 x baseline, whereas 22 of 25 (88%) with normal perfusion imaging studies had a normal distal CFVR of > 2.0 (p = 0.000 1). Thirteen of 25 patients (52%) with reversible perfusion abnormalities had transstenotic gradients > or = 20 mm Hg, whereas 20 of 25 (80%) with normal perfusion studies had gradients <20 mm Hg (p = 0.01). Quantitative angiography did not differentiate patients with normal versus abnormal myocardial perfusion imaging. Distal CFVR was correlated more significantly with myocardial perfusion imaging results (kappa = 0.76) than with pressure gradients (kappa = 0.32). Exercise and pharmacologic stress myocardial perfusion imaging abnormalities reflect diminished post-stenotic coronary flow to a greater degree than transstenotic pressure gradients.

Comparison of slow oscillating versus fast balloon inflation strategies for coronary angioplasty.

Previous studies suggest that slow and/or oscillating balloon inflation during coronary angioplasty may decrease the incidence of coronary dissection and improve clinical outcomes. To compare the effect of slow oscillating versus conventional fast inflation techniques on the incidence of severe coronary dissection during angioplasty, 622 patients were randomized to slow oscillating inflation versus fast inflation. Angiographic outcomes of the procedures and in-hospital clinical events were recorded. The primary end point of severe (type C, D, E, F) dissection occurred in 7.7% of patients undergoing slow oscillation and 6.6% of patients undergoing fast inflation (p = 0.87). Major complications (death, urgent coronary artery bypass graft surgery, stroke, abrupt closure, or Q-wave myocardial infarction) occurred in 4.7% of patients undergoing slow oscillation and 3.5% of patients undergoing fast inflation (p = 0.45). The 2 inflation strategies did not differ in the pressure at which the balloon achieved full expansion, angiographic success rate, residual stenosis, and incidence of all minor and/or major complications. We conclude that there is no benefit of slow oscillating inflation over routine fast inflation in angioplasty. Slow oscillating inflation did not dilate lesions at lower pressures, decrease the incidence of dissection or severe dissection, or reduce the incidence of adverse clinical outcomes.

Immunohistochemical characterization of immune cell composition and cytokine receptor expression in human coronary atherectomy tissue.

BACKGROUND: Prior histologic studies have examined smooth muscle cell, macrophage and thrombus constituents of atherosclerotic coronary atherectomy specimens. Lymphocytes and mononuclear leukocytes are also detectable in atherosclerotic surgical pathology specimens utilizing immunocytochemical techniques. METHODS: In order to quantify the histological contribution of cytokine receptor-expressing immunocompetent cells to human coronary artery stenoses, 30 directional atherectomy catheter biopsy specimens (wet weight < or = 10 mg) from 16 patients were snap frozen (-70 degrees C) for quantitative immunocytochemical studies. Following computer-assisted quantification of total intimal nuclei per tissue section (mean 297 +/- 177; cell density 7 +/- 5/10(4) microns 2), monoclonal antibody cytochemistry was used to identify the percentage of these cells expressing antigenic clusters of differentiation (CD) characteristic of T-lymphocytes, B-lymphocytes and monocytes. Identification of alpha (low affinity) and beta (intermediate affinity) interleukin-2 receptors on intimal cells was accomplished using a three-step streptavidin-biotin method. RESULTS: A significant percentage of intimal cells were of lymphocytic (11 +/- 13%) or monocytic (12 +/- 14%) origin, with helper T-cells (9 +/- 12%) outnumbering both suppressor T-cells (2 +/- 4%) and B-lymphocytes (1 +/- 2%). Interleukin-2 receptors were noted on 9 +/- 12% of intimal cells, including cells with a vascular smooth muscle phenotype. CONCLUSIONS: These quantitative immunocytochemical data conclusively demonstrate that lymphocytes and monocytes account for over 20% of coronary plaque cells obtained by in-vivo atherectomy, and that helper (CD4) T-cells predominate over suppressor (CD8) T-cells and B-lymphocytes. Variable interleukin-2 receptor subtype expression occurs in mononuclear leukocytes infiltrating chronic human atheroma. By applying these techniques, the therapeutic effects of cytotoxic agents on selectively targeted cytokine receptor-expressing cells may now be evaluated in vivo in small human directional coronary atherectomy specimens.

Practical coronary physiology. Clinical application of the Doppler flow velocity guide wire.

Coronary angiography incompletely delineates the physiologic consequences of many epicardial stenoses. Intracoronary translesional flow velocity measurements using the Doppler flow wire during cardiac catheterization provide immediate data discriminating the physiologic significance of coronary stenoses. The validity and accuracy of the flow wire for analyzing lesion hemodynamic significance have been confirmed in multiple studies. Flow velocity analysis provides objective criteria for refining the selection of cases for revascularization, and prospective clinical data have confirmed the safety of deferring intervention on lesions with normal physiologic assessment. Translesional and distal coronary flow velocity dynamics during procedures also provide immediate data assessing the physiologic adequacy of intervention. Impaired postintervention distal coronary flow velocity and vasodilator reserve can predict subsequent clinical events, and comparisons of flow velocity indices prestenting and poststenting suggest that physiologically inadequate results of angioplasty may be improved by additional intervention. Flow velocity assessment may also have utility in profiling the adequacy of infarct artery reperfusion following acute myocardial infarction. Evidence has been accumulated to support use of Doppler flow velocity analysis as a clinically relevant technique for improving both diagnostic and therapeutic aspects of cardiovascular medicine.

Heterogeneity of p15(E)-related polypeptides expressed by MuLV-infected cells.

The p15(E)-related polypeptides of radiation leukemia virus (RadLV)-derived viruses and of cells infected with prototype MuLV were analyzed by immunoprecipitation, SDS-PAGE, and immunofluorescence analyses. It was found that the p15(E)-related molecules of ecotropic and xenotropic viruses derived from RadLV lymphoma cell lines were distinguishable by reactivity with monoclonal anti-p15(E) antibodies and by SDS-PAGE profile. Ecotropic MuLV of RadLV origin encoded the p15(E)a antigen and produced a Pr15(E) of 20K MW. In contrast, xenotropic virus derived from RadLV did not express the p15(E)a antigen and by SDS-PAGE its Pr15(E) migrated at 21K. A previously undescribed, p15(E)-related molecule of 18.5K MW was associated with xenotropic RadLV. These differences were also reproduced by the prototype ecotropic, xenotropic, and dualtropic viruses.

Intracoronary Doppler flow velocity measurements for the evaluation and treatment of coronary artery disease.

The functional significance of coronary artery disease is often inadequately revealed by the solely anatomic information provided by coronary angiography, especially with respect to intermediate-severity stenoses and the complex lesions that result from percutaneous coronary intervention. The clinical application of coronary flow velocity measurements using the Doppler flow wire during cardiac catheterization represents a promising means for providing immediate physiologic assessment of coronary artery lesion significance. Recent correlations with translesional hemodynamics and noninvasive perfusion imaging have confirmed the accuracy and reliability of Doppler translesional flow velocity assessment. The use of intracoronary flow velocity data for functional assessment can refine the selection of patients for revascularization. Furthermore, measurements of translesional and distal coronary flow velocity dynamics during procedures provide immediate data regarding the physiologic adequacy of the intervention. The information provided by the analysis of coronary blood flow using the Doppler guide wire can serve to improve the diagnostic and therapeutic capabilities of interventional cardiology.