bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment of ventricular tachycardia by transcatheter radiofrequency ablation in patients with ischemic heart disease.
Authors: Kim Y H , Sosa-Suarez G , Trouton T G , O'Nunain S S , Osswald S , McGovern B A , Ruskin J N , Garan H 
Published: June 2012

BACKGROUND
Recurrent sustained ventricular tachycardia (VT) is not responsive to antiarrhythmic drugs in the majority of patients, who therefore need therapy with nonpharmacological methods. We evaluated prospectively the feasibility, safety, and efficacy of transcatheter radiofrequency (RF) ablation of VT in 21 selected patients with ischemic heart disease and VT.

METHODS AND RESULTS
Twenty-one patients with ischemic heart disease and recurrent, drug-refractory VT documented by 12-lead ECG were selected who had sufficient hemodynamic tolerance of VT to undergo transcatheter mapping. Documented clinical VT was reproduced by programmed cardiac stimulation (PCS), and the site of origin was localized by a combination of techniques, including pace mapping, activation-sequence mapping, recordings of middiastolic potentials, and application of resetting and entrainment principles. RF current at 55 V was applied (3.8 +/- 3.1 applications per patient) for as long as 30 seconds at a time to target sites. Twenty-four distinct clinical VTs (mean cycle length, 445 +/- 52 milliseconds) were mapped and ablated in 21 patients. In 17 of 21 patients (81%), the procedure was acutely successful, and the target clinical VT could no longer be induced by PCS after the procedure, whereas in 4 patients, clinical VT remained inducible. By contrast, VTs with shorter cycle length and different QRS morphology than the ablated VT could still be induced by PCS in 12 of 21 patients. One patient died in intractable congestive heart failure 10 days after the procedure, and the remaining 20 are alive at the end of the follow-up period. The majority of the patients continued to be treated with at least one additional mode of antiarrhythmic therapy; 12 patients were still taking antiarrhythmic drugs, and 9 patients received an implantable cardioverter/defibrillator. During a mean follow-up period of 13.2 +/- 5.0 months, 9 of 20 patients (45%) had recurrent VT. In 4 patients, the recurrent VT was different than the previously ablated one. Clinical VT recurred in all 4 patients in whom RF ablation had been acutely unsuccessful. Four patients with recurrent VT underwent repeat RF ablation procedures that were acutely successful and had no further recurrence.

CONCLUSION
Transcatheter RF ablation is feasible but has only moderately high efficacy in a small, selected group of patients with ischemic heart disease and drug-refractory, highly frequent, hemodynamically tolerated, sustained VT. In the majority of the patients, this treatment technique is palliative rather than definitive, and many of the patients continue to require other methods of antiarrhythmic therapy.
Prevalence and predictors of audible physiological third heart sound in a population sample aged 36 to 37 years.
Authors: Kupari M , Koskinen P , Virolainen J , Hekali P , Keto P 
Published: June 2012

BACKGROUND
A physiological third heart sound (S3) is common in youth but allegedly very rare after the age of 40 years. The mechanism of its disappearance is not known. The aim of this work was to study the prevalence and predictors of physiological S3 in a population-based sample of persons approaching 40 years of age.

METHODS AND RESULTS
A random sample of 120 persons born in 1954 was invited; 93 (42 men) entered the study. Their physical activity, alcohol and tobacco consumption, and salt intake were quantified by diary follow-up. The presence of an S3 was determined by auscultation and confirmed by phonocardiography. Left ventricular (LV) size, mass, and systolic function were assessed by M-mode echocardiography and LV filling by Doppler velocimetry of transmitral flow. An audible S3 was detected in 22 subjects, 1 of whom had heart disease. The prevalence of physiological S3 was 23.1%. Subjects with physiological S3 had a lower body mass index (22.3 +/- 2.8 versus 24.6 +/- 4.1 kg/m2 [mean +/- SD], P = .005), lower heart rate (63 +/- 7 versus 68 +/- 10 beats per minute, P = .015), higher peak early diastolic transmitral velocity (67 +/- 10 versus 58 +/- 8 cm/s, P = .002), and higher acceleration of early diastolic velocity (717 +/- 148 versus 622 +/- 122 cm/s2, P = .012) than those without S3. No differences were noted in the lifestyle characteristics, blood pressure, or LV mass and systolic function. Body mass index and peak early diastolic transmitral velocity were independent predictors of physiological S3 in logistic regression analysis.

CONCLUSIONS
Nearly one fourth of persons approaching their forties still have an audible physiological S3. The presence of S3 is predicted by leanness and a high early diastolic LV inflow velocity; the disappearance of S3 is unlikely to be secondary to increasing blood pressure and relative LV hypertrophy, as is widely presented, but reflects a more primary age-related alteration of LV early diastolic function.
Radiofrequency catheter ablation guided by intracardiac echocardiography.
Authors: Chu E , Fitzpatrick A P , Chin M C , Sudhir K , Yock P G , Lesh M D 
Published: June 2012

BACKGROUND
Radiofrequency catheter ablation requires precise positioning of the ablation electrode. Fluoroscopically guided catheter manipulation has limitations, and there are risks of radiation exposure. The purpose of this study was to examine the feasibility of guiding catheter ablation within the right atrium with catheter-based intracardiac echocardiography.

METHODS AND RESULTS
A 10F, 10-MHz intracardiac imaging catheter was used to direct an ablation electrode at four or five anatomic landmarks in the right atrium. Thirty-eight radiofrequency energy applications were performed in nine anesthetized dogs, and 38 lesions were identified on pathological examination. Lesions were created a mean of 1.9 +/- 2.1 mm from the ultrasound-guided site. Twenty-six of 38 lesions (68%) were less than 2.2 mm from the imaged site. Intracardiac echocardiography also was used to confirm stable electrode-endocardial contact in 37 energy applications (97%) and identified catheter movement in 9 energy applications (24%). Discrete lesions, microcavitations, and thrombi were observed in 13 (34%), 23 (61%), and 19 (50%) of 38 energy applications, respectively. Microcavitations predicted the appearance of thrombus. Fluoroscopy time required to create four or five lesions decreased from 23 minutes in the first study to less than 2 minutes in the last five studies.

CONCLUSIONS
Catheter-based intracardiac echocardiography can accurately guide catheter ablation directed at anatomic landmarks and potentially reduced ionizing radiation exposure. Intracardiac imaging can be used to confirm endocardial contact, identify electrode movement, and directly visualize lesions. Intracardiac echocardiography also can be used to identify microcavitations, which predict thrombus formation during radiofrequency energy applications.
Effects of monotherapy with an HMG-CoA reductase inhibitor on the progression of coronary atherosclerosis as assessed by serial quantitative arteriography. The Canadian Coronary Atherosclerosis Intervention Trial.
Authors: Waters D , Higginson L , Gladstone P , Kimball B , Le May M , Boccuzzi S J , Lespérance J 
Published: June 2012

BACKGROUND
3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors are widely prescribed for hyperlipidemia, yet their effect on the evolution of coronary atherosclerosis has not been defined.

METHODS AND RESULTS
To address this issue, 331 patients with diffuse but not necessarily severe coronary atherosclerosis documented on a recent arteriogram and with fasting serum cholesterol between 220 and 300 mg/dL were enrolled in a randomized, double-blind, placebo-controlled trial. All patients received intensive dietary counseling. Lovastatin or placebo was begun at 20 mg/d and was titrated to 40 and 80 mg during the first 16 weeks to attain a fasting low-density lipoprotein (LDL) cholesterol < or = 130 mg/dL. The mean lovastatin dose was 36 mg/d. Coronary arteriography was repeated after 2 years. In 299 patients (90%), 3858 coronary segments containing 2309 stenoses were measured blindly on pairs of films with an automated computerized quantitative system. Total and LDL cholesterol decreased by 21 +/- 11% and 29 +/- 11%, respectively, in the lovastatin-treated group but changed by < 2% in placebo patients. The primary end point, coronary change score, defined as the per-patient mean of the minimum lumen diameter changes (follow-up minus baseline angiogram) for all lesions measured, excluding those < 25% on both films, worsened by 0.09 +/- 0.16 mm in the placebo group and by 0.05 +/- 0.13 mm in the lovastatin group (P = .01). Progression (a worsening in minimum diameter of one or more stenoses by > or = 0.4 mm) with no regression at other sites occurred in 48 of 146 lovastatin and 76 of 153 placebo patients (33% versus 50%, P = .003). New coronary lesions developed in 23 lovastatin and 49 placebo patients (P = .001). The beneficial effect of treatment was most pronounced in the more numerous, milder lesions and in patients whose baseline total or LDL cholesterol levels were above the group median.

CONCLUSIONS
Lovastatin slows the progression of coronary atherosclerosis and inhibits the development of new coronary lesions.
Adenovirus-mediated gene transfer of soluble vascular cell adhesion molecule to porcine interposition vein grafts.
Authors: Chen S J , Wilson J M , Muller D W 
Published: June 2012

BACKGROUND
The efficacy of aorto-coronary vein grafting is limited by early graft thrombosis and accelerated graft atherosclerosis. Direct adenovirus-mediated transfer of genes encoding inhibitory proteins may prevent or slow progression of vein graft disease.

METHODS AND RESULTS
Recombinant adenoviruses containing the cDNA for the marker gene lacZ (Ad.CMVlacZ) or soluble vascular cell adhesion molecule (sVCAM) (Ad.CB-sVCAM) were used to infect segments of porcine jugular vein or human saphenous vein. Ex vivo testing showed expression of the introduced genes after incubation with Ad.CMVlacZ or Ad.CBsVCAM for periods from 1 to 24 hours, with an increase in transfection efficiency with increasing incubation time. Porcine jugular veins were then interposed as vascular grafts in the carotid arteries of four juvenile farm pigs after ex vivo gene transfer by incubation for 90 to 120 minutes with Ad.CMVlacZ or Ad.CBsVCAM. sVCAM-transfected carotid vein grafts were placed on one side and lacZ transfected veins were placed contralaterally as controls. Three days later, the vein graft segments were resected. Expression of the lacZ gene was confirmed by X-Gal chromagen staining and visualization by light and transmission electron microscopy. Gene expression was apparent in all layers of the vein graft wall, with prominent staining in the adventitia. sVCAM expression was confirmed by immunohistochemistry and in situ hybridization.

CONCLUSIONS
We conclude that ex vivo gene transfer before vein grafting is feasible using a replication-deficient recombinant adenovirus and results in a high level of gene expression in vivo. The potential for this approach to prevent early vein graft thrombosis or accelerated vein graft atherosclerosis requires further evaluation.
Nitric oxide regulates basal systemic and pulmonary vascular resistance in healthy humans.
Authors: Stamler J S , Loh E , Roddy M A , Currie K E , Creager M A 
Published: June 2012

BACKGROUND
The endothelium synthesizes and releases a relaxing factor with the physiochemical properties of nitric oxide (NO). However, the role of endothelium-derived NO in the basal regulation of systemic and pulmonary vascular resistance in humans is not known. Our primary objectives were to determine the effects of inhibiting NO synthesis on blood pressure and systemic vascular resistance and to establish the role of endothelium-derived NO in the regulation of normoxic pulmonary vascular tone.

METHODS AND RESULTS
We studied the systemic and pulmonary hemodynamic effects of NG-monomethyl-L-arginine (L-NMMA, 0.03 to 1.0 mg.kg-1.min-1 IV), an NO synthase inhibitor, in 11 healthy volunteers, aged 33 +/- 2 years. An arterial cannula and a pulmonary artery catheter were placed in each subject to measure blood pressure, pulmonary artery pressure, and pulmonary capillary wedge pressure. Cardiac output was determined by the Fick technique, and systemic and pulmonary vascular resistances were calculated. Serum NO levels (free and protein bound) were measured by chemiluminescence in 5 subjects. Six of the subjects also received phenylephrine (25 to 100 micrograms/min IV) to compare the cardiac hemodynamic effects of L-NMMA with those of a direct-acting vasoconstrictor. L-NMMA caused dose-dependent increases in both blood pressure and systemic vascular resistance. At the highest dose of L-NMMA, there was a 15.5 +/- 1.3% increase in mean blood pressure and a 63.4 +/- 8.2% increase in systemic vascular resistance (each P < .01). Pulmonary vascular resistance increased 39.8 +/- 9.4% (P < .01), whereas mean pulmonary artery pressure did not change. Administration of L-NMMA also reduced cardiac output by 27.8 +/- 2.9% and stroke volume by 15.4 +/- 3.5% (each P < .01). Serum NO levels decreased 65 +/- 10% from basal values (P < .05), confirming inhibition of endogenous NO production. Phenylephrine increased blood pressure to a level comparable to that observed with L-NMMA. The decline in stroke volume was greater with L-NMMA than with phenylephrine (P < .01).

CONCLUSIONS
This study demonstrates that basal release of endothelium-derived NO is directly involved in the determination of systemic vascular resistance and, therefore, blood pressure in healthy humans. In addition, NO regulates basal normoxic pulmonary vascular tone. The complex hemodynamic effects of NO are composite properties of its actions on systemic and pulmonary vascular resistance and cardiac function.
Magnetic resonance imaging of chronic myocardial infarcts in formalin-fixed human autopsy hearts.
Authors: Hsu J C , Johnson G A , Smith W M , Reimer K A , Ideker R E 
Published: June 2012

BACKGROUND
In post-myocardial infarction patients, three-dimensional structure of the infarct as well as infarct size are likely to be important factors affecting mortality, cardiac function, and arrhythmias. Current morphological methods for determining three-dimensional infarct structure in autopsied hearts are inexact and time consuming. The cardiac magnetic resonance imaging techniques used in living patients have shown potential in determining infarct size and structure but have limited resolution for morphometric postmortem studies. The recent development of magnetic resonance microscopy raises the possibility that three-dimensional infarct structure can be quantified at microscopic levels in autopsied hearts. The purpose of this study was to determine the ability of magnetic resonance imaging at different spatial resolutions to differentiate infarcted from noninfarcted myocardium.

METHODS AND RESULTS
Magnetic resonance imaging was performed at 2.0 T on cross sections taken from 10 autopsied hearts containing old myocardial infarcts. T1 was derived from six images with repetition times (TRs) for each image ranging from 100 to 3200 milliseconds. T2 was derived from multi-echo images with echo times (TEs) ranging from 10 to 60 milliseconds. Resolution was approximately 400 x 400 microns in 2-mm-thick slices. Sites of infarcted and noninfarcted tissue were identified from histological sections taken from each slice, and the T1 and T2 values of these sites were obtained. Microscopic images were acquired with voxels of 100 x 100 x 625 microns, representing tissue volumes more than 1000-fold smaller than conventional clinical images. In all cases, T1 of infarcted tissue (459 +/- 266 milliseconds, mean +/- SD) was greater than that of noninfarcted tissue (272 +/- 163 milliseconds). Also, in all cases, T2 of infarcted tissue (49 +/- 14 milliseconds) was greater than that of noninfarcted tissue (35 +/- 8 milliseconds).

CONCLUSIONS
T1 and T2 values for infarcted tissue are significantly different from those of noninfarcted tissue (P < .001). Based on these findings, it should be possible to develop techniques to perform three-dimensional imaging and quantitation of infarcts with a resolution of 400 microns or less. When volumetric three-dimensional imaging was performed using a T1-weighted sequence, the resulting 256(3) arrays supported isotropic resolution at 400 microns (voxel volume, 0.064 mm3). Subsequent volume rendering using a compositing algorithm clearly shows the infarcted areas in three dimensions. The techniques demonstrate the potential for quantitative three-dimensional cardiac morphometry using magnetic resonance imaging.
Antihypertensive therapy augments endothelium-dependent relaxations in coronary arteries of spontaneously hypertensive rats.
Authors: Tschudi M R , Criscione L , Novosel D , Pfeiffer K , Lüscher T F 
Published: June 2012

BACKGROUND
Coronary artery disease is an important complication of hypertension. Therefore, the effects of antihypertensive therapy on the endothelial nitric oxide (NO)/L-arginine pathway and vascular smooth muscle were studied in left anterior descending coronary arteries of Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Angiotensin II (AT1) receptor antagonists CGP 48369 and valsartan, angiotensin-converting enzyme inhibitor benazepril HCl, and calcium antagonist nifedipine were used as antihypertensive agents.

METHODS AND RESULTS
Rings were examined in myograph systems for isometric tension recording. In untreated WKY and SHR rings, acetylcholine (10(-9) to 10(-5) mol/L) but not bradykinin, substance P (both 10(-6) mol/L), or thrombin (1 U/mL) induced comparable endothelium-dependent relaxations. These relaxations were markedly decreased by NG-monomethyl-L-arginine (10(-4) mol/L) and fully prevented by N omega-nitro-L-arginine methyl ester (10(-4) mol/L) or methylene blue (10(-5) mol/L). In vitro treatment of WKY and SHR rings with benazeprilat, CGP 48369, or valsartan (3 x 10(-7) mol/L) did not affect responses to acetylcholine. In SHR, chronic therapy for 8 weeks with benazepril HCl, CGP 48369, valsartan, or nifedipine (each 10 mg.kg-1.d-1 PO) similarly reduced blood pressure and increased endothelium-dependent relaxations to acetylcholine (log shift at IC50, ie, half-maximal inhibition of a preceding contraction, 10-, 8-, 13-, and 13-fold, P < .05 versus control), whereas relaxations to the NO donor 3-morpholino sydnonimine (SIN-1, 10(-9) to 10(-5) mol/L) remained unaffected. In WKY, chronic therapy with nifedipine (10 mg.kg-1.d-1 PO) affected neither blood pressure nor relaxations to acetylcholine or SIN-1.

CONCLUSIONS
In rat coronary arteries, NO is synthesized via the endothelial L-arginine pathway and released after stimulation with acetylcholine. In SHR, chronic antihypertensive therapy with either angiotensin receptor antagonists, an angiotensin-converting enzyme inhibitor, or a calcium antagonist specifically increased the normal endothelium-dependent relaxations to acetylcholine, probably because of their blood pressure-lowering effects, whereas the responsiveness of vascular smooth muscle to NO remained unaffected.
Cardiorenal and neurohumoral effects of endogenous atrial natriuretic peptide in dogs with severe congestive heart failure using a specific antagonist for guanylate cyclase-coupled receptors.
Authors: Wada A , Tsutamoto T , Matsuda Y , Kinoshita M 
Published: June 2012

BACKGROUND
To elucidate the extent of the compensatory role of endogenous atrial natriuretic peptide (ANP) in severe congestive heart failure (CHF), we examined the changes in hemodynamics and neuroendocrine and renal functions after incremental administration of an ANP antagonist, HS-142-1 (HS), in dogs with CHF.

METHODS AND RESULTS
We assessed the effects of HS on the suppression of plasma and urinary cGMP levels as a marker of endogenous ANP activity in dogs without CHF. Bolus injections of 0.3 and 1.0 mg/kg HS reduced plasma cGMP levels to 77% and 60% and urinary cGMP excretion to 78% and 61% of the relevant control levels, respectively. Then the study was performed in dogs with CHF induced by chronic rapid ventricular pacing, and the plasma ANP level was sixfold higher than that in the controls. Hemodynamic, hormonal, and renal variables were determined both before and after subsequent incremental administration (0.3, 1.0, and 3.0 mg/kg every 30 minutes) of HS. HS lowered the plasma and urinary cGMP levels dose dependently to 32% and 37% of the control levels, respectively. Mean arterial, pulmonary capillary wedge, and right atrial pressures and cardiac output did not change significantly. However, plasma renin activity, aldosterone level, and norepinephrine level increased rapidly to 226%, 179%, and 252% of the control values, respectively. Urine flow rate and urinary sodium excretion were significantly inhibited, with no concomitant change in glomerular filtration rate or renal plasma flow.

CONCLUSIONS
These findings suggest that endogenous ANP contributes to the suppression of the activation of the renin-aldosterone system and sympathetic nervous activity and body fluid retention but that the vasodilative action of this peptide is attenuated in advanced CHF.
Thrombin-induced endothelium-dependent inhibition and direct activation of platelet-vessel wall interaction. Role of prostacyclin, nitric oxide, and thromboxane A2.
Authors: Yang Z , Arnet U , Bauer E , von Segesser L , Siebenmann R , Turina M , Lüscher T F 
Published: June 2012

BACKGROUND
Platelet-vessel wall interaction plays an important role in acute cardiovascular disorders. Thrombin is a potent platelet activator but also has profound effects on the endothelium. Endothelial cells possess antithrombotic activity by releasing nitric oxide and prostacyclin, both potent vasodilators and platelet inhibitors. We studied the role of thrombin as a regulator of platelet-vessel wall interaction in isolated human arteries suspended in organ chambers for isometric tension recording.

METHODS AND RESULTS
In arteries with endothelium, thrombin (0.01 to 1 U/mL) induced endothelium-dependent relaxations, which were reduced by the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10(-4) mol/L) and/or indomethacin (10(-5) mol/L). Human platelets (75,000/microL) evoked only marginal contractions in arteries with endothelium (3 +/- 3% of the contraction to KCl 100 mmol/L; NS), which were markedly enhanced by endothelial removal (22 +/- 4%; P < .05). Thrombin (1 U/mL) did not affect the response to platelets in arteries with (6 +/- 5%; NS) but induced a huge contraction in rings without endothelium (53 +/- 6%; P < .01 versus control without endothelium). The potent contraction to thrombin-activated platelets (1000 to 75,000/microL) in arteries without endothelium was markedly inhibited by the thromboxane A2 synthetase/receptor antagonist ridogrel (10(-5) mol/L; P < .005 versus control) and the single-acting thromboxane receptor blocker SQ-30741 (10(-7) mol/L; P < .01 versus control).

CONCLUSIONS
Thus, thrombin directly stimulates platelets to release thromboxane A2, inducing potent vasoconstriction, which is prevented by the simultaneous thrombin-induced release of prostacyclin and nitric oxide from endothelial cells. In arteries devoid of functional endothelial cells, as occurs in patients with coronary artery disease, a combined inhibition of thromboxane production and action provides a potent therapeutic tool to interfere with the thrombin-induced activation of platelet-vessel wall interaction.