bluuebunny/crossref_metadata_2025 huggingface dataset:
Altered lipid profile after Kawasaki syndrome.
Authors: Newburger J W , Burns J C , Beiser A S , Loscalzo J
Published: June 2012

BACKGROUND

Delineation of lipid values in children after Kawasaki syndrome is important because of the predilection of this disease for the coronary arteries.

METHODS AND RESULTS

We measured plasma concentrations of total cholesterol, high density lipoprotein (HDL) cholesterol, and triglycerides using enzymatic methods in 105 patients with a history of Kawasaki syndrome. Measurements were obtained during six time periods: 10 days or less, 11-31 days, 1-3 months, 3-12 months, 1-3 years, and more than 3 years. Total cholesterol was depressed in the first interval (122.0 +/- 19.8 mg/dl, mean +/- SD), but the mean values were normal in all periods after clinical recovery (overall mean, 149.0 +/- 24.0 mg/dl). High density lipoprotein cholesterol was also depressed in the first interval (15.2 +/- 9.9 mg/dl); although high density lipoprotein cholesterol increased significantly with duration since disease onset (p less than 0.001), it remained significantly lower than expected (p less than 0.001), even in the latest interval (47.2 +/- 10.9 mg/dl). Nonfasting triglyceride levels were high (162.5 +/- 63.4 mg/dl) in the first interval and then diminished steadily with time, but this relation did not achieve statistical significance. We compared adjusted lipid levels (z scores) of 46 Kawasaki patients after clinical recovery with those of their parents; patients had similar total cholesterol levels but significantly lower high density lipoprotein cholesterol levels (p = 0.021 for mothers, p = 0.001 for fathers). Mean high density lipoprotein cholesterol after clinical recovery tended to be lower in patients with persistent coronary abnormalities than in those without such lesions (p = 0.085).

CONCLUSIONS

Kawasaki syndrome is associated with important abnormalities in lipid metabolism. Continued long-term surveillance of this population is necessary to monitor lipid levels and their relation to future development of coronary atherosclerosis.
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.
Early detection of rejection and assessment of cyclosporine therapy by 111In antimyosin imaging in mouse heart allografts.
Authors: Isobe M , Haber E , Khaw B A
Published: June 2012

BACKGROUND. Mice (n = 58) with abdominal heterotopic heart transplants were studied to examine the effectiveness of 111In-labeled antimyosin scintigraphy in the detection of rejection and to determine the consequence of cyclosporine therapy on the results. METHODS AND RESULTS. Allografts from B10D2 donors were transplanted into B6AF1 recipients. Of the 49 allografted mice, 19 were treated with cyclosporine (15 mg/kg.day). Nine isografted mice served as controls. Scintigraphy was performed by injecting 100 muCi 111In antimyosin monoclonal antibody 2-15 days after transplantation. An increase in the ratio of percent dose of antimyosin injected per gram (% dose/g) of the grafted heart (G) to that of the autologous heart (A) (G/A) as well as the increasing percent dose per gram of antimyosin in the grafts reflected the severity of histopathological rejection regardless of the presence or absence of cyclosporine. Scintigraphic images demonstrated unequivocally intense accumulation of 111In in rejected allografts as confirmed by histologically demonstrable myocyte necrosis. The G/A ratio in allografted mice with mildly deteriorated mechanical activity (4.2 +/- 1.0, mean +/- SD) was greater than that in mice with normal contractility (1.8 +/- 0.7) (p less than 0.001), and the necrosis correlated with this modest decline in mechanical function could be scintigraphically identified. Of mice with normally contracting allografts, the G/A ratio was greater in animals with demonstrated myocyte necrosis (2.6 +/- 0.5) than in those without necrosis (1.5 +/- 0.5) (p less than 0.001). In contrast, isografted mice or a subset of allografted mice treated with cyclosporine and not showing evidence of rejection did not manifest any significant change in G/A ratio, nor did they have scintigrams positive for rejection as late as 15 days after transplantation. CONCLUSIONS. These findings suggest that antimyosin scintigraphy is a sensitive and early indicator of cardiac transplant rejection and that it could be useful as a noninvasive method for assessing the efficacy of cyclosporine treatment.
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.
An alpha-1-adrenergic receptor subtype is responsible for delayed afterdepolarizations and triggered activity during simulated ischemia and reperfusion of isolated canine Purkinje fibers.
Authors: Molina-Viamonte V , Anyukhovsky E P , Rosen M R
Published: June 2012

BACKGROUND

We used standard microelectrode techniques to study delayed afterdepolarizations and triggered activity induced by alpha 1-adrenergic stimulation in canine Purkinje fibers in the setting of simulated ischemia and reperfusion.

METHODS AND RESULTS

The ischemic environment included 10.8 mM [Ca2+]o, 10 mM [K+]o, 40-50 mm Hg PO2, 20 mM lactate (pH 6.7), and 1 x 10(-7) M phenylephrine. During ischemia, there was the variable occurrence of abnormal automaticity, early afterdepolarizations, and delayed afterdepolarizations. During reperfusion, 100% of preparations manifested delayed afterdepolarizations and 40% manifested triggered activity. Decreasing PO2 to less than 20 mm Hg markedly reduced the incidence of delayed afterdepolarizations and triggered activity, as did increasing PO2 to values of more than 90 mm Hg. WB 4101, an alpha 1-subtype-selective competitive blocker that antagonizes the effects of alpha 1-agonists to induce phosphoinositide metabolism and increase [Ca2+]i, significantly reduced the incidence of delayed afterdepolarizations and triggered activity. In contrast, the alpha 1-subtype-selective blocker chloroethylclonidine, an alkylating agent, had no effect on afterdepolarizations or triggered activity.

CONCLUSIONS

Our results indicate that a specific alpha 1-adrenergic pathway is involved in the induction of triggered activity in the setting of ischemia and reperfusion and suggest that interventions used to block this specific pathway have the potential to be antiarrhythmic. They also emphasize the importance of the magnitude of hypoxia in the expression of the arrhythmias.
Reduction in thrombus formation by placement of endovascular stents at endarterectomy sites in baboon carotid arteries.
Authors: Krupski W C , Bass A , Kelly A B , Hanson S R , Harker L A
Published: June 2012

BACKGROUND

Although antithrombotic therapies with aspirin, dipyridamole, and heparin have decreased thrombo-occlusive events, they have not abolished these complications. Endovascular mechanical support, first reported by Dotter in 1969, has been proposed as a means to reduce both acute and chronic vessel closure by providing a supporting framework for the disrupted and sometimes dissected arterial wall.

METHODS AND RESULTS

To determine the effects of placing self-expanding stainless steel wire endoprostheses on the accumulation of thrombus at sites of carotid artery endarterectomy we measured platelet deposition continuously for 90 minutes and at 24 and 48 hours by gamma camera imaging of autologous 111In-labeled platelets in six stented and nonstented endarterectomized baboons that received heparin but no antiplatelet agents. At nonstented endarterectomy sites 5.36 +/- 1.25 x 10(8), 4.78 +/- 0.98 x 10(8), and 4.55 +/- 0.81 x 10(8) platelets per cm were deposited at 30, 60, and 90 minutes, respectively. In contrast, stented endarterectomy sites accumulated 0.99 +/- 0.31 x 10(8), 0.66 +/- 0.33 x 10(8), and 0.80 +/- 0.36 x 10(8) platelets per cm at 30 minutes (p = 0.02), 60 minutes (p = 0.004), and 90 minutes (p = 0.002), respectively. Platelet deposition remained reduced at 24 and 48 hours in stented endarterectomized carotid arteries (ECAs) when assessed as a ratio between net radioactivity in the endarterectomized region versus whole blood radioactivity (p = 0.006 and p = 0.009, respectively). Both stented and nonstented ECAs remained patent acutely, although two of six nonstented ECAs occluded by 30 days. By comparison 11 of 14 nonstented ECAs remained patent in another group of control animals. Scanning electron microscopy of control and stented arteries at 30 days demonstrated equivalently confluent endothelium.

CONCLUSIONS

We postulate that endovascular stents reduce the thrombogenic effects of flap formation, tearing, dissection, and vasospasm in ECAs.
Effects of intravenous adenosine on antegrade refractoriness of accessory atrioventricular connections.
Authors: Garratt C J , Griffith M J , O'Nunain S , Ward D E , Camm A J
Published: June 2012

BACKGROUND

Several groups have suggested the use of intravenous adenosine or adenosine triphosphate in the diagnosis of regular broad complex tachycardias. However, the short half-life of these agents has precluded assessment of their effects on refractoriness of accessory connections, and their safety in preexcited arrhythmias has not been demonstrated.

METHODS AND RESULTS

We examined the effects of intravenous adenosine on accessory atrioventricular (AV) connections in 30 patients with the Wolff-Parkinson-White syndrome. Intravenous adenosine (12 mg, rapid bolus) was administered to 14 patients (group 1) during continuous atrial pacing at a cycle length 20 msec below that required to cause 2:1 conduction block in the accessory connection (mean pacing cycle length 261 +/- 41 msec). After adenosine, transient 1:1 conduction occurred via the accessory connection in 12 of 14 patients, indicating a shortening of antegrade refractoriness. In three of seven patients, this effect was abolished after intravenous propranolol (0.2 mg/kg). Nineteen patients (group 2) received adenosine (0.17 +/- 0.04 mg/kg) during induced, preexcited atrial arrhythmias. The minimum RR interval during preexcited atrial fibrillation transiently decreased (252 +/- 44 msec to 224 +/- 35 msec, p less than 0.01) after adenosine, but no change in average RR interval was observed (360 +/- 59 msec to 357 +/- 60 msec, NS). The preexcited ventricular response to atrial flutter was transiently accelerated in five of eight patients (415 +/- 21 msec to 360 +/- 49 msec, p less than 0.05) due to shortening of flutter cycle length (207 +/- 10 msec to 180 +/- 24 msec, p less than 0.05). However, 2:1 accessory connection conduction was maintained in all eight patients. All effects were short lived, with the decrease in RR interval during atrial fibrillation occurring for a maximum of two RR intervals only. No patient suffered ventricular arrhythmias or hemodynamic deterioration.

CONCLUSIONS

Adenosine shortens antegrade refractoriness of accessory AV connections, and in some patients this action is mediated by beta-adrenergic stimulation. Adenosine may cause acceleration of preexcited atrial arrhythmias, but these effects are transient and should not discourage the use of adenosine as a diagnostic agent in broad complex, regular tachycardias of uncertain origin.
Quinidine-related mortality in the short-to-medium-term treatment of ventricular arrhythmias. A meta-analysis.
Authors: Morganroth J , Goin J E
Published: June 2012

BACKGROUND

The interim results of the Cardiac Arrhythmia Suppression Trial requires physicians to use a higher threshold for employing antiarrhythmic agents in the treatment of benign or potentially lethal ventricular arrhythmias. Many have managed patients by switching to the traditional class I quinidine despite its known proarrhythmic tendency.

METHODS AND RESULTS

To evaluate the relation between quinidine therapy and mortality in patients with benign or potentially lethal ventricular arrhythmias, we performed a meta-analysis on four randomized double-blind active controlled parallel trials evaluating 1,009 patients in which quinidine (n = 502) was compared to flecainide (n = 141), mexiletine (n = 246), tocainide (n = 67), and propafenone (n = 53). All four trials had similar patient selection, protocols, and methodology (e.g., placebo lead-in and Holter monitoring) but varying lengths of drug exposure. A total of 12 deaths were reported on quinidine and four deaths on the other drugs: two on mexiletine, one on flecainide, and one on tocainide. The statistical analysis of the mortality rates was based on techniques for combining data across separate strata. Based on maximum likelihood estimation, the combined risk of dying on quinidine was statistically significantly higher compared to the other four drugs with a risk difference of 1.6%. The 95% confidence interval was 0-3.1% (p = 0.05). The likelihood ratio test for uniformity of the risk difference across strata showed the trials to be homogeneous (p = 0.88). There was one death recorded for the placebo lead-in period (2 weeks' exposure for 624 patients and 1 week for 385 patients), and seven deaths were reported within 2 weeks on active drug treatment--six on quinidine and one on mexiletine. Furthermore, proarrhythmia was reported in 20 patients on quinidine versus 11 patients on the four other drugs (p = 0.09).

CONCLUSIONS

These data suggest that quinidine may have an adverse effect on mortality as compared to other class I antiarrhythmic agents and that individualized patient selection for the use of this agent be carefully weighed relative to its potential for harm and benefit.
Effects of calcitonin gene-related peptide on normal and atheromatous vessels and on resistance vessels in the coronary circulation in humans.
Authors: Ludman P F , Maseri A , Clark P , Davies G J
Published: June 2012

BACKGROUND

Calcitonin gene-related peptide (CGRP) is a potent dilator of normal epicardial coronary vessels in humans, but its effects on myocardial blood flow and atheromatous coronary vessel diameter are unknown.

METHODS AND RESULTS

Seven patients were entered for study of the effects of CGRP on coronary blood flow and 13 for the comparison of its effects on normal and atheromatous coronary arteries. In the first seven patients, left anterior descending artery (LAD) diameter at an angiographically normal site, coronary sinus oxygen saturation (CSO2S), systemic blood pressure, and heart rate were measured during intracoronary infusion of increasing concentrations of CGRP (up to 200 ng/ml at 2 ml/min) followed by intracoronary adenosine (0.267 micrograms/ml at 2 ml/min) and finally intracoronary glyceryl trinitrate (GTN) (5 micrograms/ml at 2 ml/min). CGRP dilated the normal segment of the LAD by 22.6 +/- 8% (mean +/- 95% confidence interval), p less than 0.001, with only a small increase in CSO2S from 40.1 +/- 2.7% to 47.3 +/- 2.7%, p less than 0.001. Adenosine, a potent dilator of myocardial resistance vessels, caused no further increase in LAD diameter but caused a rise in CSO2S from 47.3 +/- 2.7% to 76.0 +/- 2.7%, p less than 0.001. GTN caused no further increase in LAD diameter. As heart rate-blood pressure product remained unchanged throughout the study, the increase of CSO2S indicated only a small increase in myocardial blood flow after CGRP infusion. In 13 patients with atheromatous coronary artery disease, the effects of intracoronary CGRP at angiographically normal sites, stenoses, angiographically normal sites immediately adjacent to stenoses, and sites of coronary artery wall irregularity were compared after intracoronary infusion of a single dose of CGRP (200 ng/ml at 2 ml/min) followed by intracoronary GTN (5 micrograms/ml at 2 ml/min). At these four sites, CGRP resulted in dilatation by 17.0 +/- 5.6%, 15.3 +/- 12.1% (NS), 7.6 +/- 5.4% (NS), and 15.9 +/- 7.8%, respectively. There was no significant further dilatation after GTN at any of the four sites.

CONCLUSIONS

These data indicate that CGRP has little effect in humans at rest on coronary resistance vessels in nonischemic myocardium but causes marked dilatation of normal arteries and variable dilatation of atheromatous epicardial arteries.
Evaluation of thromboxane production and complement activation during myocardial ischemia in patients with angina pectoris.
Authors: Montalescot G , Drobinski G , Maclouf J , Maillet F , Salloum J , Ankri A , Kazatchkine M , Eugène L , Thomas D , Grosgogeat Y
Published: June 2012

BACKGROUND

The complement system and arachidonic acid metabolites are involved in severe myocardial ischemia such as myocardial infarction. Furthermore, there is experimental evidence for C5a participation in thromboxane production.

METHODS AND RESULTS

We examined whether C5a and thromboxane are produced during brief and reversible episodes of myocardial ischemia induced in patients with stable angina. Twenty-five patients underwent either atrial pacing or percutaneous transluminal coronary angioplasty associated with arterial and coronary sinus blood sampling. Rapid atrial stimulation of patients with effort angina caused significant ST segment depression (delta ST = -1.7 +/- 0.2 mm), decreased fractional lactate extraction (from +12.8 +/- 2.5% baseline to -13.7 +/- 4.6% at peak ischemia, n = 13, p less than 0.001), and increased coronary sinus plasma thromboxane B2 levels (from 345 +/- 85 pg/ml baseline to 1,684 +/- 64 pg/ml at peak ischemia, p less than 0.01). Changes of fractional lactate extraction correlated significantly with changes of coronary sinus plasma levels of thromboxane B2. There was no change of coronary sinus 6-keto-PGF1 alpha levels. Similar pacing of control subjects (n = 6) did not cause release of lactate or thromboxane. Seventeen other patients underwent exercise testing with noninvasive measurements of thromboxane and prostacyclin metabolites in urinary samples collected before and after the test. No detectable increase of urinary 11-dehydrothromboxane B2 was measured in patients with stable angina after exercise-induced myocardial ischemia. However, basal 11-dehydrothromboxane B2 levels were significantly higher in patients with angina (105 +/- 25 pg/mmol creatinine, n = 9) than in control patients (45 +/- 8 pg/mmol creatinine, n = 8, p less than 0.05 between groups). Coronary sinus plasma levels of the anaphylatoxin C5a always remained below 4 ng/ml in patients undergoing pacing. More severe myocardial ischemia after coronary angioplasty (percent lactate extraction decreased from +24.8 +/- 2.7% baseline to -41.6 +/- 22.4% at peak ischemia, p less than 0.05) was not associated with C3a or C5b-9 generation. In all patients, there was neither platelet sequestration nor platelet alpha-granule release (no changes of beta-thromboglobulin/platelet factor 4 levels) into the coronary sinus plasma.

CONCLUSIONS

Patients with stable angina have chronically increased thromboxane synthesis as assessed by excretion of urinary metabolites. Thromboxane is acutely released into the coronary sinus during pacing-induced ischemia without significant intracoronary platelet aggregation. Complement does not appear to be activated in stable angina during brief and reversible episodes of myocardial ischemia and does not contribute to thromboxane production.
Catecholamine metabolic pathways and exercise training. Plasma and urine catecholamines, metabolic enzymes, and chromogranin-A.
Authors: Rogers P J , Tyce G M , Weinshilboum R M , O'Connor D T , Bailey K R , Bove A A
Published: June 2012

BACKGROUND

Because acute exercise increases systemic catecholamines, we sought to determine whether exercise training would alter daily or exercise-related catecholamine release and inactivation.

METHODS AND RESULTS

In 24-hour urine collections, catecholamines and metabolites provided indexes of overall oxidative deamination, sulfation, and O-methylation. Plasma catecholamines, the sulfoconjugates of each, and chromogranin-A were determined at rest and during exercise in 10 well-trained male subjects and nine minimally trained male subjects (maximal oxygen uptake 55.2 and 42.5 ml/kg/min, respectively), and levels of activities of catechol-O-methyltransferase (COMT), monoamine oxidase B (MAO-B), and thermolabile phenolsulfotransferase (TL-PST) were also determined. Plasma-free catecholamines showed minimal differences between the two groups at submaximal exercise (4 minutes) but large differences at maximal exercise, reflecting the different exercise levels attained. Inactivation of plasma catecholamines by sulfation across rest and exercise tended to be greater in the well-trained group, with small increases in both plasma sulfoconjugated dopamine and sulfoconjugated norepinephrine. In the well-trained group, urinary metabolites demonstrated trends toward increased dopamine release (p less than 0.07) and small increases in the daily release of epinephrine and its sulfoconjugated metabolites. Indexes of deamination, sulfoconjugation, and O-methylation, with the exception of a reduced deamination of dopamine and the activities of COMT, MAO-B, and TL-PST were not different in the two groups.

CONCLUSIONS

Despite considerable differences in the exercise activities per week between well-trained and minimally trained individuals, there were minimal differences in the release and metabolism of catecholamines at rest or during exercise.
A new configuration for right ventricular assist with skeletal muscle ventricle. Short-term studies.
Authors: Niinami H , Hooper T L , Hammond R L , Ruggiero R , Pochettino A , Colson M , Stephenson L W
Published: June 2012

BACKGROUND

Previous attempts to provide right heart assistance with skeletal muscle ventricles (SMVs) have been frustrated by the low preload supplied by the systemic venous blood pressure. In the present study, right ventricular pressure was exploited to provide more optimal preload, the SMV being connected by valved conduits between right ventricular free wall and the main pulmonary artery.

METHODS AND RESULTS

SMVs were constructed from the right latissimus dorsi muscle in seven mongrel dogs. Following a delay period of 4 weeks, SMVs were preconditioned with 2-Hz continuous stimulation for 5-6 weeks. The SMV was then connected to the right ventricle using a porcine valved Dacron conduit. A similar valved conduit connected the SMV to the main pulmonary artery that had been ligated proximally. SMVs were stimulated with 33-Hz burst frequency to contract synchronously with ventricular diastole in a 1:2 mode. The stimulator was intermittently turned off to permit comparison of assisted and nonassisted circulation. Cardiac output increased by 27% at 1 hour (1,437 +/- 54 versus 1,140 +/- 64 ml/min, p less than 0.005) and by 30% at 4 hours (1,403 +/- 161 versus 1,074 +/- 99 ml/min, p less than 0.005), systemic arterial systolic pressure increased at 1 hour by 12% (87.1 +/- 4.9 versus 78.0 +/- 4.9 mm Hg, p less than 0.05) and by 13% at 4 hours (81.4 +/- 2.8 versus 72.3 +/- 3.4 mm Hg, p less than 0.005), and peak pulmonary arterial pressure increased at 1 hour by 35% (28.0 +/- 2.1 versus 20.9 +/- 1.8 mm Hg, p less than 0.01) and by 37% at 4 hours (31.5 +/- 2.6 versus 23.0 +/- 0.4 mm Hg, p less than 0.05). Peak SMV pressure was 52.8 +/- 2.0 mm Hg at 1 hour and 49.9 +/- 3.3 mm Hg at 4 hours (p = NS).

CONCLUSIONS

The improved preload supplied by this configuration of right ventricular assist enabled an SMV to provide stable and effective circulatory support throughout the 4-hour duration of the experiment.
Doppler echocardiographic evaluation of pseudoaneurysms complicating composite grafts of the ascending aorta.
Authors: Barbetseas J , Crawford E S , Safi H J , Coselli J S , Quinones M A , Zoghbi W A
Published: June 2012

BACKGROUND

Pseudoaneurysms of the ascending aorta is a rare and serious complication after composite graft surgery for combined disorders of the aortic valve and ascending aorta.

METHODS AND RESULTS

Echocardiographic and Doppler findings are described in eight patients (seven men, one woman; mean age, 45 +/- 12 years) with documented pseudoaneurysm of the ascending aorta and are compared with those by aortography and at surgery. The diameter of the ascending aorta ranged from 6 to 14 cm. Pseudoaneurysm was diagnosed by echocardiography in seven cases (six transthoracic, one transesophageal), by aortography in five, and by both methods in all patients. All three patients not diagnosed by aortography had a single dehiscence at the aortic annulus anastomosis. Five patients had more than one site of origin of the pseudoaneurysm. Periannular dehiscence (n = 7) was identified by color flow Doppler in six cases and by aortography in only one, and coronary artery dehiscence (n = 6) was detected by echocardiography in three and by aortography in two arteries. Of the three patients with distal graft dehiscence, one was identified by aortography and none by echocardiography. In cases of dehiscence at the aortic annulus, continuous wave Doppler further supported the diagnosis by demonstrating two distinct jets, one through the prosthetic valve and another with higher velocity through the communication.

CONCLUSIONS

Echocardiography with Doppler can diagnose the presence of pseudoaneurysms complicating composite grafts and identify their proximal sites of origin. Furthermore, it complements aortography in the overall evaluation of patients with suspected pseudoaneurysm, particularly in those with single dehiscence of the graft at the aortic annulus anastomosis.