bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of impinging wall jet on color Doppler quantification of mitral regurgitation.
Authors: Chen C G , Thomas J D , Anconina J , Harrigan P , Mueller L , Picard M H , Levine R A , Weyman A E 
Published: June 2012

BACKGROUND
In clinical color Doppler examinations, mitral regurgitant jets are often observed to impinge on the left atrial wall immediately beyond the mitral valve. In accordance with fluid dynamics theory, we hypothesized that a jet impinging on a wall would lose momentum more rapidly, undergo spatial distortion, and thus have a different observed jet area from that of a free jet with an identical flow rate.

METHODS AND RESULTS
To test this hypothesis in vivo, we studied 44 patients with mitral regurgitation--30 with centrally directed free jets and 14 with eccentrically directed impinging wall jets. Maximal color jet areas (cm2) (with and without correction for left atrial size) were correlated with mitral regurgitant volumes, flow rates, and fractions derived from pulsed Doppler mitral and aortic forward flows. The groups were compared by analysis of covariance. Mean +/- SD mitral regurgitant fraction, regurgitant volume, and mean flow rate averaged 37 +/- 17%, 3.06 +/- 2.65 l/min, and 147 +/- 118 ml/sec, respectively. The maximal jet area from color Doppler imaging correlated relatively well with the mitral regurgitant fraction in the patients with free mitral regurgitant jets (r = 0.74, p less than 0.0001) but poorly in the patients with impinging wall jets (r = 0.42, p = NS). Although the mitral regurgitant fraction was larger (p less than 0.05) in patients with wall jets (44 +/- 20%) than in those with free jets (33 +/- 15%), the maximal jet area was significantly smaller (4.78 +/- 2.87 cm2 for wall jets versus 9.17 +/- 6.45 cm2 for free jets, p less than 0.01). For the same regurgitant fraction, wall jets were only approximately 40% of the size of a corresponding free jet, a difference confirmed by analysis of covariance (p less than 0.0001).

CONCLUSIONS
Patients with mitral regurgitation frequently have jets that impinge on the left atrial wall close to the mitral valve. Such impinging wall jets are less predictable and usually have much smaller color Doppler areas in conventional echocardiographic views than do free jets of similar regurgitant severity. Jet morphology should be considered in the semiquantitative interpretation of mitral regurgitation by Doppler color flow mapping. Future studies of the three-dimensional morphology of wall jets may aid in their assessment.
Cytotoxic effects of a recombinant chimeric toxin on rapidly proliferating vascular smooth muscle cells.
Authors: Epstein S E , Siegall C B , Biro S , Fu Y M , FitzGerald D , Pastan I 
Published: June 2012

BACKGROUND
Restenosis after percutaneous transluminal coronary angioplasty is associated with activation of medial smooth muscle cells (SMCs); they proliferate, migrate to the subintima, and narrow the vessel lumen. Cancer cells often express more cell surface receptors than do normal cells. This has allowed tumor cells to be specifically targeted using cytotoxic agents. We have examined whether a similar concept can be applied to rapidly proliferating but nontransformed SMCs. Pseudomonas exotoxin (PE; MW, 66 kDa) is a potent toxin that kills cells by inhibiting protein synthesis; its toxicity is diminished when its cell recognition domain is deleted to produce a 40-kDa protein (PE40).

METHODS AND RESULTS
A complementary DNA encoding transforming growth factor alpha (TGF alpha) was ligated to that encoding PE40 and the chimeric toxin TGF alpha-PE40, which is cytotoxic to cancer cells displaying epidermal growth factor (EGF) receptors, was expressed in Escherichia coli. The ability of this toxin to kill proliferating SMCs was tested. When cells were seeded at low density (2,500 cells/cm2) and grown in medium supplemented with 10% fetal bovine serum, they were found to be rapidly proliferating; these cells were very sensitive to the cytotoxic effects of TGF alpha-PE40 (ID50, 4.0 +/- 0.17 ng/ml). In contrast, cytotoxicity was 30-fold less (ID50, 125 +/- 23 ng/ml; p less than 0.0004) when cells were in a quiescent state (grown in medium supplemented with 0.5% fetal bovine serum).

CONCLUSIONS
Competition studies using excess EGF indicated that the cytotoxic effects of TGF alpha-PE40 are specifically mediated by the EGF receptor. EGF receptor binding analysis demonstrated that rapidly proliferating SMCs display 10-fold more EGF receptors than do quiescent SMCs in vitro. Thus, a chimeric toxin targeted toward the EGF receptor can selectively kill rapidly proliferating SMCs. Whether this toxin or other chimeric toxins directed against other cell surface receptors will effectively inhibit SMCs proliferating in vivo or be useful in preventing restenosis remains to be determined.
Platelet-targeted fibrinolysis enhances clot lysis and inhibits platelet aggregation.
Authors: Bode C , Meinhardt G , Runge M S , Freitag M , Nordt T , Arens M , Newell J B , Kübler W , Haber E 
Published: June 2012

BACKGROUND
Although plasminogen activator therapy has been shown to reduce mortality in patients with severe myocardial infarction, several problems fuel the search for more potent and specific thrombolytic agents.

METHODS AND RESULTS
To explore the effect of plasminogen activator targeting to platelets, we covalently linked urokinase that had been modified with N-succinimidyl-3-(2-pyridyldithio)propionate to the Fab' of a monoclonal antibody (7E3) that selectively binds to platelet membrane glycoprotein (GP) IIb/IIIa. In an assay measuring (as reflected by plasmin generation) a plasminogen activator's ability to bind GP IIb/IIIa immobilized on plastic, urokinase-7E3 Fab' produced 31-fold more plasmin than did urokinase (p = 0.0001). The addition of solubilized GP IIb/IIIa blocked this enhancement of plasmin generation, indicating that binding was impaired. Plasmin generation reflecting binding to immobilized intact platelets was 2.4-fold greater for urokinase-7E3 Fab' than for unconjugated urokinase (p = 0.002). In a plasma clot lysis assay, urokinase-7E3 Fab' was at least 25-fold more potent than either urokinase alone or a mixture of urokinase and 7E3 (Fab')2 (p less than 0.009), and potency could be related to platelet concentration in the clot. Ex vivo, ADP-induced platelet aggregation was inhibited by a urokinase-7E3 IgG conjugate at a concentration of 8 nM, whereas a mixture of urokinase and 7E3 (Fab')2 in equimolar amounts required 60 nM and urokinase alone required 1 microM to achieve the same effect.

CONCLUSIONS
Therefore, the targeting of urokinase to the GP IIb/IIIa platelet receptor both accelerates clot lysis (when platelets are associated with a fibrin clot) and inhibits platelet aggregation.
Anatomy of the tricuspid annulus. Circumferential myofibers as the structural basis for atrial flutter in a canine model.
Authors: Racker D K , Ursell P C , Hoffman B F 
Published: June 2012

BACKGROUND
Little anatomic information is available on the annular myocardium. This study was conducted to determine the anatomic substrate for atrial flutter due to circus movement around the tricuspid annulus in the Y-shaped incision canine model of atrial flutter.

METHODS AND RESULTS
We studied photographs of the annular myocardium serial histological sections, made in either of three different planes, and compared these with photographs of the intact and blocked gross heart specimens. We found that the annulus is the most caudal region of the atrial wall. The epicardial aspect of the annulus abuts the ventricular septum or the aortic root in the medial region; in other regions, it is covered by the fat of the coronary sulcus. Its endocardial aspect is delimited by the tricuspid leaflets inferiorly and by the pectinate muscle bundles superiorly, except in the medial region where the pectinate muscle bundles are absent. The annular myocardium is bilaminated. A continuous subepicardial circumferential lamina is the most prominent and is robust in the anterior, lateral, and posterior regions, but it attenuates to a fine muscular connection in the medial region. Myofibers of its superior border merge with the pectinate muscle bundles or are admixed in the medial region with myocardium at the base of the medial atrial wall. Its inferior border makes little contact with the annulus fibrosus about the ring; however, in the medial region, these myofibers insert into fibrous tissue superior to the septal leaflet. A discontinuous, subendocardial perpendicular lamina contains myofibers that descend from the atrium; most of these myofibers insert into the annulus fibrosus about the ring, but the lamina is absent in the anteromedial region.

CONCLUSIONS
We conclude that the continuous circumferential lamina provides the anatomic substrate for circus movement of excitation in this model.
Instantaneous hyperemic flow-versus-pressure slope index. Microsphere validation of an alternative to measures of coronary reserve.
Authors: Mancini G B , Cleary R M , DeBoe S F , Moore N B , Gallagher K P 
Published: June 2012

BACKGROUND
The instantaneous hyperemic flow-versus-pressure (i-HFVP) slope index is a new method of assessing maximal coronary conductance and can be used as an alternative to conventional measures of coronary reserve. The i-HFVP slope index is determined by measuring the slope of the linear diastolic segment of the relation between instantaneous aortic pressure and hyperemic coronary flow.

METHODS AND RESULTS
To validate the i-HFVP slope index as a measure of maximal coronary conductance, we compared this method with a microsphere-derived measurement of maximal coronary conductance (m-HFVP slope index) by determining the slope of the least-squares regression line of the data points for coronary flow during maximal hyperemia and four or five steady-state alterations of aortic pressure in 43 dogs (open-chest, anesthetized preparations) with or without coronary stenoses. The i-HFVP slope index demonstrated no dependence on heart rate, left ventricular end-diastolic pressure, or mean aortic pressure and was highly reproducible within the groups studied (intraclass correlation coefficient, 0.86 for normal arteries, 0.87 for stenotic arteries, and 0.93 for combined groups; for all coefficients, p less than 0.001). The i-HFVP slope index was significantly decreased in the presence of a stenosis (10.3 +/- 3.9 for normal arteries versus 3.6 +/- 1.6 for stenotic arteries, p less than 0.001) as was the transmural m-HFVP slope index (8.9 +/- 4.6 for normal arteries versus 5.3 +/- 3.1, p less than 0.01). Of special importance, the i-HFVP slope index measurement for normal arteries was not significantly different from the transmural and subendocardial m-HFVP slope index measurements (10.3 +/- 3.9 versus 8.9 +/- 4.6 and 9.2 +/- 5.7, respectively). For stenotic arteries, the i-HFVP slope index measurement was also not significantly different from the transmural and subendocardial m-HFVP slope index measurements (3.6 +/- 1.6 versus 5.3 +/- 3.1 and 4.1 +/- 2.3, respectively). The i-HFVP slope index correlated best with subendocardial m-HFVP slope index measurements (correlation coefficient, 0.57; p less than 0.001). When the 95% confidence intervals for the transmural (or subendocardial) m-HFVP slope index in normal arteries were compared with the i-HFVP slope index values, the latter demonstrated a systematic trend to overestimate the m-HFVP slope index. In the presence of a stenosis, this effect was minimized, and the slope values were nearly identical.

CONCLUSIONS
The i-HFVP slope index correlates most closely with subendocardial coronary conductance; the index is a hemodynamically independent measure of coronary reserve that is reproducible over a broad range of aortic pressures; and the methodology is applicable to an intact circulation in experimental preparations and may with future developments also prove useful in humans.
Improved blood flow during prolonged cardiopulmonary resuscitation with 30% duty cycle in infant pigs.
Authors: Dean J M , Koehler R C , Schleien C L , Atchison D , Gervais H , Berkowitz I , Traystman R J 
Published: June 2012

BACKGROUND
Sustained compression is recommended to maximize myocardial and cerebral blood flow during cardiopulmonary resuscitation (CPR) in adults and children. We compared myocardial and cerebral perfusion during CPR in three groups of 2-week-old anesthetized swine using compression rates and duty cycles (duration of compression/total cycle time) of 100 per minute, 60%; 100 per minute, 30%; and 150 per minute, 30%.

METHODS AND RESULTS
Ventricular fibrillation was induced and CPR was begun immediately with a sternal pneumatic compressor. Epinephrine was continuously infused during CPR. Microsphere-determined blood flow and arterial and sagittal sinus blood gas measurements were made before cardiac arrest was induced and after 5, 10, 20, 35, and 50 minutes of CPR. At 5 minutes of CPR, ventricular and cerebral blood flows were greater than 25 ml.min-1 x 100 g-1 and were not significantly different between groups. When CPR was prolonged, however, myocardial and cerebral blood flows were significantly higher with the 30% duty cycle than with the 60% duty cycle. By 35 minutes, all myocardial regions had less than 5 ml.min-1 x 100 g-1 flow with the 60% duty cycle. In contrast, CPR with the 30% duty cycle at either compression rate provided more than 25 ml.min-1 x 100 g-1 to all ventricular regions for 50 minutes. By 20 minutes, most brain regions received 50% less flow with the 60% duty cycle compared with animals undergoing CPR with the 30% duty cycle (p less than 0.05). Cerebral oxygen uptake was better preserved with the 30% duty cycle. Chest deformation from loss of recoil was greater with the 60% duty cycle compared with the 30% duty cycle.

CONCLUSIONS
We conclude that the shorter duty cycle provides markedly superior myocardial and cerebral perfusion during 50 minutes of CPR in this infant swine model. These data do not support recommendations for prolonged compression at rates of 100 per minute during CPR in infants and children.
Epicardial and endocardial mapping of ventricular tachycardia in patients with myocardial infarction. Is the origin of the tachycardia always subendocardially localized?
Authors: Kaltenbrunner W , Cardinal R , Dubuc M , Shenasa M , Nadeau R , Tremblay G , Vermeulen M , Savard P , Pagé P L 
Published: June 2012

BACKGROUND
Left ventricular endocardial reentry is the conventional concept underlying surgery for ventricular tachycardia (VT). We assessed the incidences of patterns showing complete reentry circuits at either the subendocardial or subepicardial level and of patterns in which left ventricular endocardial mapping could only in part account for a reentrant mechanism.

METHODS AND RESULTS
We retrospectively analyzed epicardial and left ventricular endocardial isochronal maps of 47 VTs induced in 28 patients with chronic myocardial infarction (inferior, 14 patients; anteroseptal, 14 patients). Electrograms were recorded intraoperatively from 128 sites with epicardial sock and transatrial left ventricular endocardial balloon electrode arrays. Given the methodology used in this study, the mapping characteristics of the tachycardias suggested five types of activation patterns: 1) complete (90% or more of VT cycle length) subendocardial reentry circuits in seven VTs (15%) and seven patients (25%), 2) complete subepicardial reentry circuits in four VTs (9%) and four patients (14%), 3) incompletely mapped circuits with a left ventricular endocardial breakthrough preceding the epicardial breakthrough in 25 VTs (53%) and 21 patients (75%), 4) incompletely mapped circuits with a left ventricular epicardial breakthrough preceding the endocardial breakthrough in three VTs (6%) and three patients (11%), and 5) a right ventricular epicardial breakthrough preceding the left ventricular endocardial breakthrough in eight VTs (17%) and seven patients (25%). After surgery, one type 3 VT and three type 5 VTs were reinducible. Thus, left ventricular endocardial reentry substrates (types 1 and 3) accounted for 68% of VTs, but substrates involving subepicardial (types 2 and 4) and deep septal layers (type 5) accounted for 32% of VTs.

CONCLUSIONS
In a substantial number of VTs, a substrate localization that is at variance with the conventional concept can be detected by simultaneous epicardial and endocardial mapping and may require modification of the surgical approach conventionally aimed at endocardial layers.
Anomalous insertion of papillary muscle directly into anterior mitral leaflet in hypertrophic cardiomyopathy. Significance in producing left ventricular outflow obstruction.
Authors: Klues H G , Roberts W C , Maron B J 
Published: June 2012

BACKGROUND
Obstruction to left ventricular outflow in hypertrophic cardiomyopathy (HCM) is usually due to systolic anterior motion of the mitral valve. Occurrence of structural mitral valve abnormalities in HCM and their significance in producing outflow obstruction (even in the absence of typical systolic anterior motion) has not been fully appreciated.

METHODS AND RESULTS
Analysis of 78 mitral valves excised from patients with obstructive HCM showed that 10 (13%) had anomalous insertion of one or both left ventricular papillary muscles directly into the anterior mitral leaflet. This malformation was identified by echocardiography, which demonstrated direct continuity between the hypertrophied papillary muscle and mitral leaflet, resulting in a long rigid area of midcavity narrowing that appeared to be solely or largely responsible for outflow obstruction. Basal subaortic pressure gradients were large (70-150 mm Hg). Mitral valve replacement reduced the outflow gradient substantially to 0-15 mm Hg in four patients with postoperative cardiac catheterization. However, two other patients who underwent septal myotomy/myectomy had persistent symptoms and incomplete relief of obstruction (gradients 60 and 70 mm Hg) because of continued midcavity apposition of papillary muscle and ventricular septum.

CONCLUSIONS
Anomalous papillary muscle insertion into anterior mitral leaflet represents a mechanism of obstruction to left ventricular outflow in patients with HCM and differs considerably from typical dynamic obstruction caused by mitral valve systolic anterior motion that occurs in many other patients with HCM. Recognition of this malformation emphasizes the diverse morphological expression of HCM and also has important clinical implications for patients requiring operation because the gradient is likely to persist even after adequate myotomy/myectomy; consequently, mitral valve replacement would appear to be the operation of choice in most such patients.
Transmural distribution of myocardial tissue growth induced by volume-overload hypertrophy in the dog.
Authors: Omens J H , Covell J W 
Published: June 2012

BACKGROUND
Although chronic volume overload is thought to induce uniform cardiac enlargement, the stimulus for tissue growth has not been defined. Changes in diastolic and systolic stress or strain have been proposed as mechanical factors that may stimulate hypertrophy. Since there are thought to be transmural variations in these stresses and strains, three-dimensional patterns of myocardial tissue growth may provide insight into the role of these factors.

METHODS AND RESULTS
To assess the transmural variation in tissue growth after volume overload, the configurations of three columns of four to six gold beads (1-mm diameter) implanted in the left ventricular anterior free wall were recorded in five dogs before and after cardiac enlargement induced by creating a systemic arteriovenous fistula. Data were obtained with end-diastolic pressures adjusted to the same level in the control and hypertrophic states. End-diastolic wall thickness remained constant, whereas left ventricular diameter increased. Small increases in transmural systolic strain were seen. The volumes defined by four beads (a tetrahedron) at end diastole showed increases in myocardial mass of 20-27% after 3.6 (mean) weeks of hypertrophy and were uniform across the wall of the left ventricle. The edges of single bilinear-quadratic finite elements were fitted to the three columns of the bead set at end diastole in control and at end diastole after hypertrophy at equal end-diastolic pressures. Thus, continuous transmural strain distribution were obtained at the hypertrophic state with respect to the control state. The transmural distributions of these end-diastolic growth strains were uniform and positive for both the circumferential and longitudinal components measured in a cardiac coordinate system, with small radial growth strain indicating that growth was predominantly parallel to the epicardial tangent plane. Moreover, when strains were transformed (rotated) to fiber coordinates, in-plane fiber and cross-fiber growth strains were both positive at all locations across the wall and approximately equal in magnitude, indicating considerable growth in the cross-fiber direction.

CONCLUSIONS
These results indicate that the stimulus for volume-overload hypertrophy may be constant across the wall and that substantial cross-fiber growth occurs during volume-overload hypertrophy.
Dissolution of peripheral arterial thrombi by ultrasound.
Authors: Ariani M , Fishbein M C , Chae J S , Sadeghi H , Michael A D , Dubin S B , Siegel R J 
Published: June 2012

BACKGROUND
We have previously shown that continuous-wave ultrasound can rapidly dissolve human thrombi in vitro, with 99% of all residual particles measuring less than 10 microns in diameter. To assess the effects of pulsed-wave ultrasound energy on whole blood clots, 1) in vitro studies were preformed to assess precisely the rates of clot disruption and to quantify particulate size, and 2) in vivo studies were performed to assess the efficacy and safety of catheter-delivered ultrasound for intra-arterial thrombus dissolution.

METHODS AND RESULTS
In vitro, we studied 50 samples of human whole blood clots and using an 89-cm-long wire probe, applied pulse-wave energies from 8 to 23 W. The corresponding peak-to-peak tip displacement range was 63.5 - 102 microns. We studied arterial thrombosis in vivo in 21 canine superficial femoral arteries. To produce an acute thrombosis, 200 units of thrombin followed by 2 ml of 72-hour-old autologous clot were injected into a 5-7-cm segment of femoral artery and left to coagulate for 2 hours. Ultrasound energy was intermittently applied at a frequency of 20 kHz with a prototype ultrasound wire ensheathed in a catheter and directed to clots by fluoroscopy. In nine cases, angioscopic guidance was used to put the probe into direct contact with the intra-arterial thromboses. In vitro clot dissolution times were inversely related to the ultrasound power output (r = 0.95). All in vivo canine thromboses were disrupted in 4 minutes or less. All successful recanalizations were confirmed by angiography and in nine cases by angioscopy as well. Angioscopy demonstrated that probe activation caused rapid clot disruption. Histological studies of the vessels showed no evidence of thermal or cavitation injury, occlusive distal embolization, or perforation.

CONCLUSIONS
Our findings in this experimental canine model suggest that ultrasound clot dissolution has the potential to be an effective and safe alternative to current treatment modalities for peripheral arterial thrombosis.