bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasma fibrinopeptide A levels in patients with acute myocardial infarction treated with alteplase. Correlation with concomitant heparin, coronary artery patency, and recurrent ischemia. The European Cooperative Study Group.
Authors: Rapold H J , de Bono D , Arnold A E , Arnout J , De Cock F , Collen D , Verstraete M 
Published: June 2012

BACKGROUND
Fibrin generation during and after therapy with alteplase may depend on the level of concomitant anticoagulation. The hypothesis that fibrinopeptide A (FPA) levels, as markers of ongoing in vivo fibrin formation, correlate with the angiographic and clinical outcome of thrombolysis is tested.

METHODS AND RESULTS
Serial plasma FPA levels were determined in 334 patients of the randomized European Cooperative Study Group trial comparing heparin versus placebo plus alteplase and aspirin in patients with acute myocardial infarction. Median FPA levels (with the 10th to 90th percentiles) were 21 ng/ml (2-390 ng/ml) before treatment in placebo-allocated patients (n = 166) and increased to 49 (15-580), 34 (4-320), 27 (2-240), 29 (2-430), and 30 (3-390) ng/ml after 0.75, 3, 12, 24, and 36 hours, respectively. In heparin-allocated patients (n = 168), median baseline FPA values were 18 ng/ml (2-210 ng/ml) and decreased to 6 (1-110), 5 (1-75), 5 (1-60), 7 (1-100), and 10 (1-170) ng/ml at corresponding time points (p less than 0.0001 for the difference at each time point). Adequate anticoagulation, defined as no activated partial thromboplastin time value below twice the pretreatment value at 3, 12, 24, and 36 hours after initiation of treatment, was obtained in 48 patients assigned to heparin. It was associated with normal median FPA levels (less than or equal to 4 ng/ml) at all time points compared with 12 (2-80), 16 (2-240), and 15 (2-240) ng/ml at 12, 24, and 36 hours, respectively, in heparin-assigned but inadequately anticoagulated patients (n = 102, p less than 0.001 for each time point). In the heparin-treated group, median FPA values tended to be lower at all time points in patients with patent vessels than in patients with occluded arteries, but the difference was significant only at 24 hours (p = 0.04). FPA levels did not correlate with clinically apparent recurrent ischemia or with left ventricular thrombosis on two-dimensional echocardiography.

CONCLUSIONS
During and after thrombolytic therapy with alteplase, the enhanced fibrin generation is suppressed by sustained concomitant anticoagulation with intravenous heparin. Adequate anticoagulation warrants individual titration of the heparin dose. High plasma FPA levels 24 hours after alteplase therapy are specific but insensitive markers of vessel occlusion in anticoagulated patients. They do not correlate with clinical outcome.
In vitro effect of plasmin on human platelet function in plasma. Inhibition of aggregation caused by fibrinogenolysis.
Authors: Gouin I , Lecompte T , Morel M C , Lebrazi J , Modderman P W , Kaplan C , Samama M M 
Published: June 2012

BACKGROUND
Plasmin has been reported both to activate platelets and to inhibit platelet functions. The latter effect was thought to be caused by proteolysis of the main membrane glycoproteins.

METHODS AND RESULTS
We found that incubation of citrated human platelet-rich plasma with streptokinase (SK) (300 IU/ml) does not produce any detectable activation but leads to a time-dependent inhibition of ADP-induced aggregation accompanied by substantial fibrinogenolysis. These effects were abrogated by previous addition of a plasmin inhibitor, aprotinin. Crossover experiments (SK-treated or control platelets mixed with SK-treated or control plasma) demonstrated that the platelets remained functional and that the aggregation defect was caused by fibrinogenolysis. Further experiments (addition of purified fibrinogen to fibrinogen-depleted plasma with either SK or thrombin) suggested that in addition to the low residual level of fibrinogen, fibrinogen degradation products had an inhibitory effect. Under the same conditions, tissue-type plasminogen activator (t-PA) (3,000 ng/ml) had no effect on platelet aggregation, and plasma fibrinogen was not significantly lowered. The effects on glycoproteins IIb-IIIa of incubation with SK, t-PA, or plasmin were assessed with immunoblots with murine monoclonal antibodies directed against either part of the complex, which is the receptor for fibrinogen. Proteolysis was detected only in the presence of EDTA, a potent chelator of divalent cations.

CONCLUSIONS
The incubation of human platelets in citrated plasma with SK concentrations obtained during therapy leads to an aggregation defect that is related to the decrease in fibrinogen, the adhesive protein involved in this function, and to the impeding effect of fibrinogen degradation products on its binding onto platelets but not to an alteration of the corresponding platelet receptor, the heterodimer glycoproteins IIb-IIIa.
Assessment of severity of mitral regurgitation by measuring regurgitant jet width at its origin with transesophageal Doppler color flow imaging.
Authors: Tribouilloy C , Shen W F , Quéré J P , Rey J L , Choquet D , Dufossé H , Lesbre J P 
Published: June 2012

BACKGROUND
The ability of transesophageal color Doppler echocardiography to provide high-resolution images of both cardiac structure and blood flow in real time is advantageous for many clinical purposes. This study was performed to determine the utility of the regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging in the assessment of severity of mitral regurgitation.

METHODS AND RESULTS
Sixty-three consecutive patients with mitral regurgitation underwent transesophageal color Doppler examination, and the diameter of regurgitant jet at its origin was measured. Both right and left cardiac catheterizations were performed within 24 hours of Doppler studies, and angiographic grading of mitral regurgitation and regurgitant stroke volume were evaluated. There was a close relation between the jet diameter at its origin measured by transesophageal Doppler color flow imaging and the angiographic grade of mitral regurgitation (r = 0.86, p less than 0.001). A jet diameter of 5.5 mm or more identified severe mitral regurgitation (grade III or IV) with a sensitivity of 92%, specificity of 92%, and positive and negative predictive values of 88% and 95%, respectively. In 31 patients with isolated mitral regurgitation, the jet diameter correlated well with the regurgitant stroke volume determined by a combined hemodynamic-angiographic method (r = 0.85, p less than 0.001). A jet diameter of 5.5 mm or more identified a regurgitant stroke volume of 60 ml or more with a sensitivity of 88%, specificity of 93%, and positive and negative predictive values of 94% and 87%, respectively.

CONCLUSIONS
The regurgitant jet width at its origin measured by transesophageal Doppler color flow imaging provides a simple and useful method of measuring the severity of mitral regurgitation, and it may allow differentiation between mild and severe mitral regurgitation.
Metabolic responses of hibernating and infarcted myocardium to revascularization. A follow-up study of regional perfusion, function, and metabolism.
Authors: Marwick T H , MacIntyre W J , Lafont A , Nemec J J , Salcedo E E 
Published: June 2012

BACKGROUND
The presence of persistent myocardial uptake of 18F-deoxyglucose (FDG) within hypoperfused, dysfunctional segments has been shown to predict the recovery of regional contractile function after revascularization. The spectrum of metabolic responses of such hibernating tissue to revascularization is less clear.

METHODS AND RESULTS
Sixteen patients with previous infarction were studied before and after revascularization by myocardial perfusion imaging using 82Rb positron emission tomography, digitized two-dimensional echocardiography, and imaging of postexercise FDG uptake. Hibernation was identified in 35 of 85 segments showing perfusion and wall motion disturbances before intervention. At follow-up (4.9 +/- 2.6 months after revascularization), hibernating segments were characterized by reduction of wall motion score (p less than 0.001), improvement of perfusion (p less than 0.001), and reduction of FDG activity (p less than 0.001). Of the 35 hibernating segments, however, 10 still had abnormal elevation of FDG uptake (greater than 2 SD above normal) without differing from other hibernating segments with respect to postoperative perfusion or wall motion score. Segments with persistently abnormal metabolism were characterized before intervention by more severe malperfusion (p less than 0.01) and greater FDG activity (p less than 0.01).

CONCLUSIONS
Although wall motion and perfusion improve with revascularization of hibernating tissue, myocardial metabolism remains abnormal in a significant proportion of segments. These segments are characterized by more extensive perfusion and metabolic changes before revascularization.
Plasma endothelin in chronic heart failure.
Authors: McMurray J J , Ray S G , Abdullah I , Dargie H J , Morton J J 
Published: June 2012

BACKGROUND
Endothelins are recently characterized vasoconstrictor peptides. As chronic heart failure (CHF) is characterized by peripheral arteriolar and renal vasoconstriction, we have measured venous plasma endothelin-like immunoreactivity ("endothelin") in patients with this syndrome.

METHODS AND RESULTS
Compared with age- and sex-matched healthy volunteers (mean +/- SEM plasma endothelin concentration 6.4 +/- 0.3 pmol/l, n = 16), patients with severe CHF had elevated peripheral venous endothelin concentrations (12.4 +/- 0.6 pmol/l, n = 47, p less than 0.01). Plasma endothelin did not increase with exercise in normal subjects or in patients. Plasma endothelin concentration (mean, 13.4 +/- 0.9 pmol/l) did not correlate with plasma atrial natriuretic factor concentration (mean, 88.9 +/- 11.9 pg/ml) in patients with CHF (n = 21). There was also no correlation between plasma endothelin and serum urea or between endothelin and serum creatinine in patients with CHF (n = 34). There was, however, significant renal extraction of endothelin (aorta, 11.1 +/- 0.8 pmol/l; renal vein, 8.8 +/- 0.6 pmol/ml; p = 0.02) in patients with CHF (n = 13).

CONCLUSIONS
Evidence suggests that circulatory endothelin concentrations in the range 5-40 pmol/l are vasoactive. Consequently, the endothelin concentrations found in patients with CHF may be of pathophysiological significance.
Brief ischemia-reperfusion induces stunning of endothelium in canine coronary artery.
Authors: Kim Y D , Fomsgaard J S , Heim K F , Ramwell P W , Thomas G , Kagan E , Moore S P , Coughlin S S , Kuwahara M , Analouei A 
Published: June 2012

BACKGROUND
Brief ischemic episodes that induce stunning of the myocardium may also induce stunning of the coronary endothelium. To test this hypothesis, we examined both in vivo and in vitro responses of canine coronary arteries exposed to brief ischemia.

METHODS AND RESULTS
Functional recovery of the endothelium was examined in vivo during reperfusion after 15 minutes of ischemia. Vasodilatory responses to acetylcholine were severely impaired during the first hour of reperfusion but gradually improved over a 90-minute period after ischemia. The vasoconstrictive response to U46619 was enhanced for the first 30 minutes of reperfusion and returned to normal within 60 minutes. In vitro vasomotor responses to potassium chloride, acetylcholine, bradykinin, and sodium nitroprusside were examined in isolated segments of canine coronary arteries preexposed in vivo to brief ischemia (10-30 minutes) and 20 minutes of reperfusion. The results showed enhanced contractile responses and blunted endothelium-dependent but not endothelium-independent vasodilatory responses of arterial rings subjected to 10 minutes of ischemia. Twenty and 30 minutes of ischemia completely impaired endothelium-dependent vasodilation. When reperfusion was extended to 120 minutes after 15 minutes of ischemia, vasodilatory responses to acetylcholine had recovered by almost 90%. Examination of endothelial integrity by transmission electron microscopy after 10-15 minutes of ischemia revealed no evidence of structural damage. Twenty and 30 minutes of ischemia induced cytoplasmic vacuolation, partial detachment of endothelium, and swelling of cytoplasmic organelles.

CONCLUSIONS
These data support the hypothesis that brief ischemia-reperfusion induces stunning of endothelium in which endothelium-dependent vasodilatory function is impaired temporarily without morphological damage.
Lack of myocardial perfusion immediately after successful thrombolysis. A predictor of poor recovery of left ventricular function in anterior myocardial infarction.
Authors: Ito H , Tomooka T , Sakai N , Yu H , Higashino Y , Fujii K , Masuyama T , Kitabatake A , Minamino T 
Published: June 2012

BACKGROUND
We investigated myocardial perfusion dynamics after thrombolysis and its clinical implications.

METHODS AND RESULTS
We studied 39 patients with acute anterior myocardial infarction (AMI). Myocardial contrast echocardiography (MCE) was performed before and immediately after successful reflow with intracoronary injection of sonicated Ioxaglate. The average segmental score by two-dimensional echocardiography (graded 0, normal, to 3, akinetic/dyskinetic) and global ejection fraction (left ventricular ejection fraction, LVEF%) by left ventriculography were measured at 1 day and at 4 weeks after reflow. Hypokinesis in the infarct region was assessed by the centerline method and expressed in terms of standard deviations (regional wall motion [RWM]: SD/chord) of normal. Immediately after reflow, 30 of 39 patients (group A) showed significant contrast enhancement within the risk area. The other nine patients (23%, group B), however, showed the residual contrast defect in the risk area (myocardial no reflow). There were no significant differences in the elapsed time, angiographic collateral grade, and degree of residual stenosis between group A and group B. Before reflow, both groups exhibited similar levels of global and regional left ventricular function. Improvement in global (LVEF, average segmental score) and regional left ventricular function was greater in group A than in group B (average segmental score, 0.44 +/- 0.41 versus 0.97 +/- 0.36, p less than 0.01; LVEF, 56.4 +/- 13.4 versus 42.7 +/- 8.9, p less than 0.05; RWM, -1.87 +/- 0.85 versus -3.18 +/- 0.52, p less than 0.005).

CONCLUSIONS
MCE demonstrates that angiographically successful reflow cannot be used as an indicator of successful myocardial reperfusion in AMI patients. The residual contrast defect in the risk area demonstrated immediately after reflow is a predictor of poor functional recovery of the postischemic myocardium.
Identification of alpha- and beta-cardiac myosin heavy chain isoforms as major autoantigens in dilated cardiomyopathy.
Authors: Caforio A L , Grazzini M , Mann J M , Keeling P J , Bottazzo G F , McKenna W J , Schiaffino S 
Published: June 2012

BACKGROUND
Immunization with cardiac myosin induces experimental autoimmune heart disease in genetically predisposed mice. These mice produce heart-specific autoantibodies, some of which are directed against the cardiac myosin isoform.

METHODS AND RESULTS
We have reported the presence of circulating heart-specific autoantibodies in 26% of patients with idiopathic dilated cardiomyopathy (DCM) using indirect immunofluorescence. To identify the autoantigen(s) recognized by heart-specific autoantibodies in human disease, we tested, by Western blotting, sera from 26 DCM patients, 14 of whom were cardiac antibody-positive and 12 antibody-negative, as well as sera from 12 patients with cardiac failure from ischemic or valvular heart disease and from 13 normal subjects who were cardiac antibody-negative. Crude myofibrillar proteins and myosin preparations extracted from human atrial or ventricular specimens were used as antigens. Sodium dodecyl sulfate polyacrylamide gel electrophoresis was performed. The proteins were electrophoretically transferred to nitrocellulose sheets. The paper strips were incubated in sera from patients or controls at 1:100 dilution; the reaction was revealed with a peroxidase-labeled second antibody against human immunoglobulin. Twelve of the 14 DCM sera (86%) containing heart-specific antibodies reacted with both the alpha- (atrial specific) and beta- (ventricular and slow skeletal) myosin heavy chain isoforms; none of the 13 normal sera (p = 0.0001) and one of the 24 heart failure-negative control sera (4%, p = 0.0001) contained antibodies against myosin heavy chain.

CONCLUSIONS
These findings indicate that alpha- and beta-cardiac myosin heavy chain isoforms as in the murine model of autoimmune heart disease are major autoantigens in patients with idiopathic DCM.
Alterations of skeletal muscle in chronic heart failure.
Authors: Drexler H , Riede U , Münzel T , König H , Funke E , Just H 
Published: June 2012

BACKGROUND
The present study was designed to define the prevalence and characteristics of skeletal muscle alterations in patients with chronic heart failure (CHF) and their relation to exercise capacity.

METHODS AND RESULTS
The ultrastructure of skeletal muscle was analyzed by ultrastructural morphometry in 57 patients with CHF and 18 healthy controls. The volume density of mitochondria (Vvm) and the surface density (Svmc) of mitochondrial cristae were evaluated as a structural correlate of oxidative capacity of skeletal muscle. Vvm and Svmc were reduced by approximately 20% in patients with severe CHF irrespective of age and etiology. The cytochrome oxidase activity in mitochondria as determined by cytochemistry and subsequent morphometry in a subset of patients (n = 10) was significantly decreased in heart failure (p less than 0.01). The capillary length density of skeletal muscle was reduced in CHF (n = 12, p less than 0.05), and the fiber type distribution was shifted to type II fibers (n = 15, p less than 0.05). Vvm and Svmc were significantly related to peak exercise VO2 (r = 0.56, p less than 0.001, n = 60) and to VO2 at anaerobic threshold (r = 0.535, p less than 0.0001, n = 60). In 16 patients with severe heart failure, Vvm was inversely related to the duration of heart failure (r = 0.545, p less than 0.03). In 11 patients who underwent repeat biopsies after 4 months, a correlation was observed between the change in Vvm and the change in peak exercise VO2 (r = 0.89, p less than 0.001).

CONCLUSIONS
These findings indicate that patients with CHF develop significant ultrastructural abnormalities of skeletal muscle reflecting a depressed oxidative capacity of working muscle. It appears that these alterations of skeletal muscle contribute to the decreased exercise capacity of these patients but are, in principle, reversible by an effective treatment regimen.
Increased thromboxane biosynthesis in type IIa hypercholesterolemia.
Authors: Davì G , Averna M , Catalano I , Barbagallo C , Ganci A , Notarbartolo A , Ciabattoni G , Patrono C 
Published: June 2012

BACKGROUND
Increased platelet thromboxane (TX)A2 production has been described in type IIa hypercholesterolemia. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo, we studied the urinary excretion of its major enzymatic metabolites in 46 patients with type IIa hypercholesterolemia and 20 age-matched controls.

METHODS AND RESULTS
Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. The excretion rate of 11-dehydro-TXB2 was significantly (p less than 0.001) higher in patients (68.7 +/- 35.1 ng/hr, mean +/- SD) than in controls (22.4 +/- 9.4 ng/hr), with metabolite excretion greater than 2 SD of the normal mean in 74% of the patients. Urinary 11-dehydro-TXB2 was significantly (p less than 0.01) correlated with the threshold aggregating concentration of collagen (r = -0.641) and arachidonate (r = -0.734) and with agonist-induced platelet TXB2 production in vitro (r = 0.647 and 0.748, respectively). Moreover, a statistically significant correlation (r = 0.673, p less than 0.001, n = 66) was found between 11-dehydro-TXB2 excretion and total plasma cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 6 months) significantly reduced cholesterol levels by 22-28% and urinary 11-dehydro-TXB2 excretion by 32-42% in 10 patients. However, the reduction in the latter did not correlate with the reduction in the former and may have resulted from a nonspecific effect of simvastatin. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin (50 mg/day for 7 days) was associated with cumulative inhibition of 11-dehydro-TXB2 excretion by approximately 70% in six patients.

CONCLUSIONS
TXA2 biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia; this is, at least in part, a consequence of abnormal cholesterol levels, as suggested by the correlation between the two. Low-dose aspirin can largely suppress increased metabolite excretion, thus suggesting that it reflects TXA2-dependent platelet activation in vivo.
Inhibition of endothelium-derived relaxing factor enhances endothelin-mediated vasoconstriction.
Authors: Lerman A , Sandok E K , Hildebrand F L , Burnett J C 
Published: June 2012

BACKGROUND
The endothelium possesses the ability to modulate vascular tone by the release of vasodilators and vasoconstrictors, among them endothelium-derived relaxing factor (EDRF) and endothelin (ET). Abnormalities in EDRF generation have been demonstrated in various cardiovascular pathophysiological states. Moreover, a twofold increase in plasma ET concentration was reported in these disease states. Recent in vitro studies have suggested the interaction between these two endothelium-derived substances, suggesting that imbalance between the two may contribute to alternation in vascular tone characteristic of these disease states. Thus, the hypothesis of this study was that inhibition of endogenous EDRF will enhance the vasoconstrictor response to a twofold increase in plasma ET concentrations.

METHODS AND RESULTS
Experiments were conducted in three groups of anesthetized dogs. In group 1, ET-1 was infused intravenously to double circulating ET concentrations. Group 2 received both ET and NG-monomethyl L-arginine (L-NMMA), a competitive inhibitor of EDRF generation, and group 3 received a continuous infusion of L-NMMA alone. Twofold increase in plasma ET concentrations was characterized by an increase in systemic and renal vasoconstriction. The inhibition of EDRF markedly enhanced the vasoconstriction to ET specifically involving the systemic, pulmonary, coronary, and renal arterial circulations.

CONCLUSIONS
The present study demonstrates that inhibition of endogenous EDRF augments the vasoconstrictor property of ET and supports a functional role for the balance between endothelium-derived vasodilating and vasoconstricting factors in the regulation of vascular tone.