bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving detection of coronary morphological features from digital angiograms. Effect of stenosis-stabilized display.
Authors: Eigler N L , Eckstein M P , Mahrer K N , Whiting J S 
Published: June 2012

BACKGROUND
We have developed a digital display method that stabilizes the motion of a stenosis in sequential frames of a coronary angiogram, allowing it to be scrutinized at high display frame rates. The purpose of this study was to determine whether this technique improves visual detection of low-contrast luminal morphological features.

METHODS AND RESULTS
An observer detection study was conducted using computer-simulated arterial segments containing known target features, inserted into clinical digital coronary angiograms. Four observers performed a forced-choice detection of a simulated filling defect in each of 320 angiograms using the conventional and stenosis-stabilized dynamic displays (at 7.5, 15, and 32 frames per second) and a single-frame static display (total of 8960 detections). In a second simulated clinical task, three observers detected a bridging stenotic lumen in 600 angiograms using the two displays (3600 detections). In a third experiment, two angiographers rated the likelihood of intraluminal thrombus in 89 right coronary digital angiograms by consensus reading with both dynamic displays. Detectability of the simulated filling defect was similar for both dynamic display methods at 7.5 frames per second (averaging twice that for static images). As display rate was increased to 32 frames per second, detectability for the conventional display declined, whereas the stabilized display detectability increased for all observers (P < .05). On average, stabilization allowed detection of filling defects equivalent to a 71% increase in feature contrast. Response time for the conventional display averaged 12.9 +/- 4.7 seconds. For the stenosis-stabilized display, response time fell with increased frame rate (P < .05) to 4.9 +/- 1.2 seconds at 32 Hz, similar to the time for static images (4.6 +/- 0.8 seconds). The detectability of the bridging stenotic lumen was increased by 62% with the stabilization compared with conventional dynamic display (P < .00001). Consensus reading of coronary angiograms showed differences between the two dynamic display methods (kappa = 0.11) that may be explained by an improvement in observer uncertainty. A rating of definite for thrombus present or absent was more frequent with the stabilized display (39% versus 15%, P < .0001).

CONCLUSIONS
These data suggest that stabilized display of coronary angiograms significantly increases detectability, reduces the time required for detection, and improves observer uncertainty for the presence of small luminal morphological features. The method of angiographic display may thus have an impact on clinical coronary angiographic interpretation.
Expression of type 1 plasminogen activator inhibitor in chronic pulmonary thromboemboli.
Authors: Lang I M , Marsh J J , Olman M A , Moser K M , Loskutoff D J , Schleef R R 
Published: June 2012

BACKGROUND
Chronic thromboembolic pulmonary hypertension is the result of nonresolving pulmonary emboli that lead to chronic obstruction of the central pulmonary arteries.

METHODS AND RESULTS
To determine if the failure to lyse pulmonary thromboemboli is caused by the local expression of the primary inhibitor of tissue-type plasminogen activator (type 1 plasminogen activator inhibitor, PAI-1), levels of PAI-1 antigen and mRNA were analyzed by immunohistochemistry and in situ hybridization in specimens harvested from a series of patients during pulmonary thromboendarterectomies. Red, fibrin-rich thrombi within the thromboendarterectomy specimens were lined with a single layer of endothelial cells exhibiting high levels of PAI-1 antigen. Quantitation of the in situ hybridization signal revealed that a significant increase in PAI-1 mRNA was present in the endothelial cells lining the fresh thrombi in comparison to the signal present in the endothelial cells from noninvolved areas of patients' pulmonary arteries (n = 16, P < .001). In contrast, tissue-type plasminogen activator antigen levels were low in all samples. Yellowish-white thrombi were composed of smooth muscle cells and endothelial cells in numerous vessels that stained prominently for PAI-1 antigen. Both types of cells within the highly organized tissues also exhibited elevated PAI-1 mRNA levels in comparison to patient pulmonary artery specimens that were free of thrombus (n = 16, P < .02).

CONCLUSIONS
The prevalence of PAI-1 expression within pulmonary thromboemboli suggests that this inhibitory may play a role in the stabilization of vascular thrombi.
In vivo blockade of tumor necrosis factor-alpha in cholesterol-fed rabbits after cardiac transplant inhibits acute coronary artery neointimal formation.
Authors: Clausell N , Molossi S , Sett S , Rabinovitch M 
Published: June 2012

BACKGROUND
We previously identified in piglet cardiac allografts an immunoinflammatory response in coronary arteries in which increased fibronectin regulated by interleukin-1 beta was associated with early evidence of intimal thickening. In the present study, we used rabbits to assess whether acute neointimal formation after cardiac transplantation was reduced by blockade of tumor necrosis factor (TNF)-alpha, which modulates interleukin-1 beta, or by cyclosporine A.

METHODS AND RESULTS
Sixteen rabbits underwent heterotopic cardiac transplantation and were given saline, TNF-soluble receptor (sr), or cyclosporine A. In host hearts from saline- or TNFsr-treated groups, few coronary arteries (approximately 13% to 16%) had intimal thickening, whereas values were higher in the cyclosporine A-treated group (approximately 30%). In donor hearts from the saline-treated group, however, approximately 68% of vessels had intimal thickening versus approximately 32% in TNFsr- and approximately 30% in cyclosporine A-treated groups (P < .01 for both). Severity of intimal thickening assessed quantitatively as percent vessel area was approximately 38% in the saline-treated group but reduced in TNFsr- and cyclosporine A-treated groups to approximately 22% and 18%, respectively (P < .01 for each). Immunohistochemistry revealed increased staining for major histocompatibility complex II, T cells, interleukin-1 beta, TNF-alpha, and fibronectin in donor coronary arteries from saline-treated animals when compared with TNFsr- and cyclosporine A-treated animals. Grade 3 myocardial rejection was observed in both saline- and TNFsr-treated groups, but only grade 1 was apparent in the cyclosporine A-treated group.

CONCLUSIONS
In vivo blockade of TNF-alpha suppresses the acute development of neointimal formation by selectively reducing the vascular immunoinflammatory reaction and accumulation of fibronectin, whereas cyclosporine A suppresses both the myocardial and the vascular immune reaction.
Alterations in coronary artery vascular reactivity of hypertensive Ren-2 transgenic rats.
Authors: Tschudi M R , Noll G , Arnet U , Novosel D , Ganten D , Lüscher T F 
Published: June 2012

BACKGROUND
The renin-angiotensin system and endothelium-derived nitric oxide (EDNO) are important regulators of vascular tone. This study was designed to investigate endothelial and vascular smooth muscle function in coronary arteries of Ren-2 transgenic rats.

METHODS AND RESULTS
Left anterior descending coronary arteries and aortas were isolated from transgenic rats and Sprague-Dawley control rats at 6 (young) and 12 (adult) weeks of age and examined in myographs or organ chambers for isometric tension recording. Systolic blood pressure was significantly higher in transgenic rats (young, 229 +/- 6 mm Hg; adult, 239 +/- 8 mm Hg) than in control rats (young, 126 +/- 2 mm Hg; adult, 118 +/- 3 mm Hg; P < .005). N omega-Nitro-L-arginine methyl ester (L-NAME, 10(-7) to 10(-4) mol/L) evoked marked endothelium-dependent contractions in coronary arteries (young, 52 +/- 8% of the contraction to 100 mmol/L KCl; adult, 40 +/- 8%) but not aortas (young, 3 +/- 1%; adult, 2 +/- 1%). In coronary arteries, this response was significantly smaller in adult (n = 9) than in young (n = 8, P < .05) control rats. Young transgenic rats (56 +/- 9%, n = 8) showed slightly stronger contractions in response to L-NAME than young control rats (NS), which almost totally disappeared in adult transgenic rats (6 +/- 3%, n = 7; P < .05 versus adult control rats; P < .01 versus young transgenic rats). Endothelium-dependent relaxations in response to acetylcholine (10(-9) to 10(-4) mol/L) were totally blocked by L-NAME (10(-4) mol/L) but were unaffected by the thromboxane receptor antagonist SQ30741 (10(-7) mol/L). This stimulated release of EDNO, endothelium-independent relaxations in response to the nitrovasodilator linsidomine (10(-9) to 10(-5) mol/L), and contractions in response to KCl (100 mmol/L) were comparable in all groups of rats.

CONCLUSIONS
Ren-2 transgenic rats develop fulminant hypertension that is associated with a selective decrease in endothelium-dependent contractions in response to L-NAME, whereas endothelium-dependent relaxations in response to acetylcholine as well as smooth muscle function remain unaffected.
New Na(+)-H+ exchange inhibitor HOE 694 improves postischemic function and high-energy phosphate resynthesis and reduces Ca2+ overload in isolated perfused rabbit heart.
Authors: Hendrikx M , Mubagwa K , Verdonck F , Overloop K , Van Hecke P , Vanstapel F , Van Lommel A , Verbeken E , Lauweryns J , Flameng W 
Published: June 2012

BACKGROUND
Experiments were carried out using the new Na(+)-H+ exchange inhibitor (3-methylsulfonyl-4-piperidinobenzoyl)guanidine methanesulfonate (HOE 694) to assess the role of Na(+)-H+ exchange in myocardial ischemic and reperfusion injury.

METHODS AND RESULTS
Three groups of rabbit hearts (n = 5 in each) were perfused with blood and were subjected to 45 minutes of global normothermic (37 degrees C) ischemia, followed by 1 hour of reperfusion. Group 1 was the control group (vehicle only); in group 2, HOE 694 (1 mumol/L) was administered before ischemia (pretreatment group); and in group 3, HOE 694 was given only during reperfusion to separate actions exerted during ischemia from those specifically obtained during reperfusion. End-diastolic pressure rise at 1 hour of reperfusion was reduced by administration of HOE 694 starting before ischemia (from 52.2 +/- 8.5 mm Hg in group 1 to 17.6 +/- 4.5 mm Hg in group 2, P < .01) or starting on reperfusion (28.8 +/- 5.4 mm Hg in group 3, P < .05 versus group 1). Left ventricular developed pressure (LVDP) and its derivative (dP/dt) recovered better in HOE 694-pretreated hearts (LVDP, 79 +/- 9.9 mm Hg in group 2 versus 24.8 +/- 10 mm Hg in group 1; dP/dt, 1580 +/- 198 mm Hg/s versus 340 +/- 221 mm Hg/s, P < .01). In hearts treated only on reperfusion, some improvement was observed, which, however, did not reach statistical significance. Coronary flow on reperfusion was higher in groups 2 and 3 compared with controls, and no "no-reflow" was observed. Two additional groups of hearts were perfused with phosphate-free Krebs-Henseleit solution to enable studies with 31P nuclear magnetic resonance (NMR). ATP was better preserved in HOE 694-pretreated (62 +/- 4.9% of preischemic value) than in control hearts (44 +/- 3.3%) at the end of 30 minutes of reperfusion, and phosphocreatine resynthesis was higher (109 +/- 3.7% versus 86 +/- 5.4%). HOE 694 did not affect the time course of intracellular acidosis during ischemia but suppressed a small alkaline overshoot occurring early in reperfusion (pH 6.96 +/- 0.02 in HOE 694-pretreated hearts versus 7.14 +/- 0.05 in control hearts). Electron microscopy with Ca2+ staining of the blood-perfused hearts showed that clumping of Ca2+ aggregates in mitochondria was prevented by HOE 694.

CONCLUSIONS
Postischemic dysfunction was associated with a rise in end-diastolic pressure. This rise was effectively blocked by HOE 694. The drug was most effective when hearts were treated before ischemia, although partial protection was observed when administration was started on reperfusion. The action of HOE 694 strengthens the idea that Na(+)-H+ exchange during both ischemia and reperfusion contributes to contractile dysfunction.
Effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of left ventricular dysfunction and dilation in dogs with reduced ejection fraction.
Authors: Sabbah H N , Shimoyama H , Kono T , Gupta R C , Sharov V G , Scicli G , Levine T B , Goldstein S 
Published: June 2012

BACKGROUND
Recent clinical trials have suggested that therapy with angiotensin-converting enzyme inhibitors in asymptomatic patients with reduced left ventricular (LV) function can significantly reduce the incidence of congestive heart failure compared with patients receiving placebo. In the present study, we examined the effects of long-term monotherapy with enalapril, metoprolol, and digoxin on the progression of LV systolic dysfunction and LV chamber enlargement in dogs with reduced LV ejection fraction (EF).

METHODS AND RESULTS
LV dysfunction was produced in 28 dogs by multiple sequential intracoronary microembolizations. Embolizations were discontinued when LVEF was 30% to 40%. Three weeks after the last embolization, dogs were randomized to 3 months of oral therapy with enalapril (10 mg twice daily, n = 7), metoprolol (25 mg twice daily, n = 7), digoxin (0.25 mg once daily, n = 7), or no treatment (control, n = 7). As expected, in untreated dogs, LVEF decreased (36 +/- 1% versus 26 +/- 1%, P < .001) and LV end-systolic volume (ESV) and end-diastolic volume (EDV) increased during the 3-month follow-up period (39 +/- 4 versus 57 +/- 6 mL, P < .001, and 61 +/- 6 versus 78 +/- 8 mL, P < .002, respectively). In dogs treated with enalapril or metoprolol, LVEF remained unchanged or increased after therapy compared with before therapy (35 +/- 1% versus 38 +/- 3% and 35 +/- 1% versus 40 +/- 3%, respectively, P < .05), whereas ESV and EDV remained essentially unchanged. In dogs treated with digoxin, EF remained unchanged but ESV and EDV increased significantly.

CONCLUSIONS
In dogs with reduced LVEF, long-term therapy with enalapril or metoprolol prevents the progression of LV systolic dysfunction and LV chamber dilation. Therapy with digoxin maintains LV systolic function but does not prevent progressive LV enlargement.
Arrhythmogenic influence of intracoronary thrombosis during acute myocardial ischemia.
Authors: Goldstein J A , Butterfield M C , Ohnishi Y , Shelton T J , Corr P B 
Published: June 2012

BACKGROUND
Patients with acute coronary artery thrombosis often develop primary malignant ventricular arrhythmias (MVA) early after coronary occlusion. In contrast, acute ischemia induced by nonthrombotic balloon occlusion during routine coronary angioplasty rarely elicits such arrhythmias. This study was designed to assess the role of intracoronary thrombosis in arrhythmogenesis during acute ischemia.

METHODS AND RESULTS
We compared the incidence of MVA associated with acute left anterior descending coronary artery (LAD) thrombosis elicited in open-chest anesthetized dogs by electrical injury (n = 10) or intracoronary stent (n = 9) versus LAD balloon occlusion (n = 15). Compared with animals subjected to balloon occlusion, those with thrombotic occlusion had a significantly greater incidence of MVA, defined as nonsustained ventricular tachycardia (total duration > 10 seconds), sustained ventricular tachycardia, or ventricular fibrillation developing within the first 30 minutes of occlusion. In the combined thrombosis groups, MVA developed in 11 of 19 animals (58%) (6 of 10 dogs with electrical injury and 5 of 9 stent animals). In contrast, MVA occurred in only 1 of 15 animals (7%) subjected to balloon occlusion. This striking and significant difference in arrhythmias occurred despite the fact that radioactive microsphere perfusion analysis documented that the extent of left ventricular myocardium rendered ischemic was equal in all groups (percent of left ventricular myocardium with occlusion flow < or = 50% of baseline: electrical injury, 25.2 +/- 5.3%; stent, 27.1 +/- 3.6%; balloon, 34.3 +/- 11.6%; P = NS). Furthermore, there were no differences between the animals with thrombosis or balloon occlusion with respect to changes in echocardiographic parameters of left ventricular function, aortic pressure, or heart rate after occlusion.

CONCLUSIONS
These data provide evidence that despite equal magnitudes of jeopardized myocardial mass, acute ischemia induced by thrombotic coronary occlusion results in a greater incidence of MVA than does nonthrombotic balloon occlusion. These findings suggest that the process of intracoronary thrombosis itself exerts arrhythmogenic effects above and beyond the impact of ischemia on myocardium induced by coronary occlusion.
Digital angiographic assessment of the physiological changes to the regional microcirculation induced by successful coronary angioplasty.
Authors: Schühlen H , Eigler N L , Zeiher A M , Rombach M M , Whiting J S 
Published: June 2012

BACKGROUND
Impulse response analysis of digital coronary angiographic images calculates a parameter known as the mean transit time of the microcirculation (Tmicro). This has been shown to accurately assess the regional microcirculatory response to proximal stenosis in relation to flow. Our goal was to apply impulse response analysis to patients undergoing successful angioplasty and to quantify the induced physiological changes with respect to quantitative angiographic measurements of stenosis dimensions.

METHODS AND RESULTS
We studied 24 patients before and after successful single-vessel percutaneous transluminal coronary angioplasty (PTCA). Minimal luminal stenosis area was increased from 0.9 +/- 0.6 before PTCA to 4.1 +/- 1.3 mm2 after PTCA (P < .0001). In all patients this was accompanied by an increase in the inverse of Tmicro (Tmicro-1), from 8.5 +/- 3.0 to 26.5 +/- 9.0 min-1 (P < .0001) with a linear correlation between Tmicro-1 and minimal luminal stenosis area (r = .73; SEE = 7.74). Stenosis flow reserve, estimated by integration of stenosis dimensions, increased in all patients from 1.8 +/- 1.0 to 4.5 +/- 0.4 after PTCA (P < .01). A comparison of Tmicro-1 with stenosis flow reserve revealed a nonlinear relation. In 16 patients undergoing PTCA of the left anterior descending or circumflex artery, contrast injections into the left main stem allowed simultaneous measurements of Tmicro-1 in the adjacent, nonstenotic artery. Adjacent artery Tmicro-1 did not change after PTCA (25.8 +/- 6.2 compared with 25.6 +/- 6.8 min-1 before PTCA; P = NS); moreover, Tmicro-1 of the dilated artery measured after PTCA was equivalent to the nonstenotic adjacent artery, indicating normalization of microcirculatory responses.

CONCLUSIONS
These data suggest that Tmicro-1 determined by digital angiographic impulse response analysis of a single contrast injection under resting flow conditions may be a practical method to assess the regional microcirculatory response to changes in stenosis severity effected by coronary angioplasty.
Circadian variation of sustained ventricular tachycardia in patients with coronary artery disease and implantable cardioverter-defibrillators.
Authors: Lampert R , Rosenfeld L , Batsford W , Lee F , McPherson C 
Published: June 2012

BACKGROUND
While previous studies using epidemiological data and ambulatory ECG monitoring have shown peak occurrence of sudden death and nonsustained ventricular tachycardia in the morning, none have examined circadian variation of potentially life-threatening ventricular tachycardia (VT), nor has any study observed circadian behavior of any arrhythmias in individuals followed longitudinally. We used the event memory of multiprogrammable implantable cardioverter-defibrillators to evaluate the circadian pattern of sustained VT over time.

METHODS AND RESULTS
Data were reviewed from 32 consecutive patients with coronary artery disease and sustained VT who had received the Ventak PRX (CPI, Inc) cardioverter-defibrillator between May 1991 and August 1993 and had experienced at least one episode of VT terminated by their device. Mean follow-up was 14 +/- 7 months. Among the 2558 episodes recorded by the device logs, VT occurrence peaked between 6 AM and noon (P = .007 by ANOVA among four 6-hour time periods). Harmonic regression revealed a morning peak at 9 AM (P < .01). This morning peak occurred in patients with both frequent and infrequent events. Among 21 patients who experienced more than four VT events, 8 (38%) had an AM peak of VT occurrence (> 35% of VT between 6 AM and noon). Neither age, ejection fraction, event frequency, presenting arrhythmia, nor drug therapy distinguished patients who displayed the AM VT peak.

CONCLUSIONS
In patients with coronary artery disease, sustained VT displays circadian variation with peak frequency in the morning, similar to that for sudden death. Individual patients who display specific patterns of circadian variation over time can be identified using defibrillator logs. Investigation of circadian variation of other phenomena to elucidate mechanisms of VT should focus on these patients.
Enhanced detection of distinguishing features in signal-averaged electrocardiograms from patients with ventricular tachycardia by combined spatial and spectral analyses of entire cardiac cycle.
Authors: Kavesh N G , Cain M E , Ambos H D , Arthur R M 
Published: June 2012

BACKGROUND
Signals generated by myocardium responsible for ventricular tachycardia (VT) contribute to the entire QRS complex, ST segment, and T wave and are spatially distributed over the entire torso. However, current methods of signal-averaged ECG analysis restrict interrogation to the terminal QRS complex, do not include data on the body surface distributions of the distinguishing features detected, and have a limited clinical value because of a low positive predictive accuracy. Accordingly, we tested the hypothesis that frequency analysis of the entire cardiac cycle of spatially selected ECGs based on isoharmonic maps of the body surface enhance the detection of the unique spectral features in signal-averaged ECGs that differentiate patients with from those without VT.

METHODS AND RESULTS
Isoharmonic maps of the body surface were calculated during sinus rhythm with the use of forward problem solutions for 32 patients with sustained VT, 30 without VT, and 10 healthy subjects and analyzed over a bandwidth of 0.05 to 470 Hz. Spectra of ECGs at the maximum and minimum of each patient's isoharmonic map of 1 to 7 Hz demonstrated a broadened bandwidth of significant separation (P < .05) for patients with from those without VT compared with the separation achieved with the use of Frank ECGs alone. Furthermore, the statistical significance within the bands of separation was greater for spatially selected ECGs compared with the Frank leads. Frank leads separated patients over the band from 11 to 84 Hz with a mean value of P = .0094. ECGs at the maximum of 1-to-7-Hz isoharmonic maps separated patients over the 8-to-111-Hz band with a mean value of P = .0062 (range, P < .05 to P < .0000001). ECGs at the minimum of 1-to-7-Hz isoharmonic maps extended the low-frequency end of the band of separation, which covered 0 to 69 Hz with a mean value of P = .0039 (range, P < .05 to P < .0000001). Subgroup analysis verified that results were independent of QRS duration.

CONCLUSIONS
Spectral analysis of ECGs that are spatially selected for each patient is superior to orthogonal ECGs and augments detection of distinguishing features in ECGs that identify risk of VT. The new data acquired from analysis of spatially selected ECGs from individual patients provide the information on the specific frequency bands and an improved ECG-lead system required to refine methods of analysis of the signal-averaged ECG.