bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhancement of endothelium-dependent vasodilation by low-dose nitroglycerin in patients with congestive heart failure.
Authors: Schwarz M , Katz S D , Demopoulos L , Hirsch H , Yuen J L , Jondeau G , LeJemtel T H 
Published: June 2012

BACKGROUND
Since organic nitroesters and endothelium-derived nitric oxide mediate vasodilation through a final common pathway, that is, by activation of soluble guanylate cyclase in vascular smooth muscle, nitroglycerin (NTG) could specifically enhance the endothelium-dependent vasodilatory response to acetylcholine (Ach) in patients with congestive heart failure (CHF) and endothelial cell dysfunction. Accordingly, the net effects of an intra-arterial infusion of NTG (10(-9) mol/L) on endothelium-dependent and endothelium-independent vasodilation were assessed in the forearm circulation of patients with CHF.

METHODS AND RESULTS
The forearm blood flow responses to intra-arterial administration of graded concentrations of Ach (10(-7) to 10(-5) mol/L) were determined by venous occlusion plethysmography (mL/min per 100 mL) in 18 patients with CHF and 5 age-matched normal subjects before and during intra-arterial infusion of NTG (10(-9) mol/L) for 20 minutes. In eight patients, the duration of the infusion of NTG (n = 5) or vehicle control solution (n = 3) was extended to 12 hours with measurement of the forearm blood flow responses to Ach at 20 minutes, 4 hours, and 12 hours. In five additional patients, forearm blood flow response to intra-arterial administration of two doses of phentolamine (0.05 and 0.5 mg) were determined before and during a 20-minute NTG infusion. Regional administration of NTG 10(-9) mol/L did not change resting forearm blood flow in either normal subjects or patients with CHF. Before administration of NTG 10(-9) mol/L, intra-arterial infusions of Ach 10(-7), 10(-5) and 10(-5) mol/L increased forearm blood flow to 14.7 +/- 6.2, 20.2 +/- 4.7, and 38.4 +/- 7.9 mL/min per 100 mL in normal subjects and to 4.1 +/- 0.8, 5.0 +/- 1.1, and 10.6 +/- 2.3 mL/min per 100 mL in patients with CHF. After administration of NTG 10(-9) mol/L for 20 minutes, the vasodilatory response to Ach significantly increased to 5.6 +/- 1.0, 6.9 +/- 1.6, and 17.7 +/- 3.4 mL/min per 100 mL in patients with CHF but did not change in normal subjects. The enhanced forearm blood flow responses to administration of Ach observed after 20 minutes of NTG administration in patients with CHF were sustained throughout a 12-hour NTG infusion. In contrast, regional administration of NTG did not change the vasodilatory responses to phentolamine.

CONCLUSIONS
NTG, when administered intra-arterially for 20 minutes at a dose that does not affect resting forearm blood flow, specifically increased the vasodilatory response to intra-arterial administration of Ach in patients with CHF but not in normal subjects. The vasodilatory response to Ach was consistently enhanced by low-dose NTG throughout a 12-hour period. The vasodilating effects of organic nitroesters on the peripheral vasculature of patients with CHF may result in part from an interaction with the vascular endothelium.
Cardiovascular responses during static exercise. Studies in patients with complete heart block and dual chamber pacemakers.
Authors: Alexander T , Friedman D B , Levine B D , Pawelczyk J A , Mitchell J H 
Published: June 2012

BACKGROUND
During static exercise in normal subjects, the mean arterial pressure increases as a result of an increase in heart rate and thereby cardiac output with no significant change in stroke volume or systemic vascular resistance. We hypothesized that if one component of the blood pressure response to static exercise, ie, heart rate, were fixed, plasticity of the neural control mechanisms during exercise would allow for preservation of the blood pressure response by alternative mechanisms.

METHODS AND RESULTS
Thirteen patients 20 to 68 years old with structurally normal hearts, complete heart block, and dual chamber pacemakers performed static exercise during three conditions: (1) normal dual chamber sensing and pacing mode, (2) heart rate fixed at the resting value obtained in the DDD mode of 78 +/- 4 beats per minute, and (3) heart rate fixed at the peak value obtained during exercise in the DDD mode of 94 +/- 4 beats per minute. Heart rate, blood pressure, and cardiac output were measured and stroke volume and systemic vascular resistance were calculated at rest and at 1 and 5 minutes during static one-leg extension at 20% of maximal voluntary contraction. The mean arterial pressures at rest and at 5 minutes were higher when the heart rate was fixed at the faster peak exercise heart rate. In the DDD mode, heart rate increased by 16 beats per minute and cardiac output by 1.1 L/min, with a resultant 25 mm Hg increase in mean arterial pressure at 5 minutes with no change in the stroke volume or systemic vascular resistance. In both fixed heart rate pacing modes, mean arterial pressure increased by 24 mm Hg when the heart rate was fixed at the resting heart rate and by 25 mm Hg when the heart rate was fixed at the faster peak exercise heart rate pacing modes associated with an increase in stroke volume, with similar increases in cardiac output. During static exercise there was no change in systemic vascular resistance from the resting value in any pacing mode.

CONCLUSIONS
When heart rate is fixed in the presence of normal left ventricular function, the mean arterial pressure increases normally during static exercise because of an increase in stroke volume with no change in the systemic vascular resistance.
Radiofrequency ablation therapy in idiopathic left ventricular tachycardia with no obvious structural heart disease.
Authors: Wen M S , Yeh S J , Wang C C , Lin F C , Chen I C , Wu D 
Published: June 2012

BACKGROUND
The feasibility and efficacy of radiofrequency ablation therapy in idiopathic left ventricular tachycardia has not been assessed in a large group of patients.

METHODS AND RESULTS
Twenty consecutive patients with idiopathic left ventricular tachycardia and without structural heart disease underwent electrophysiological study, pharmacological interventions with administration of verapamil and adenosine, and radiofrequency ablation therapy. There were 17 men and 3 women with a mean age of 28 +/- 8 years. The QRS configuration during tachycardia was of right bundle branch block and superior axis in 13 patients, indeterminate axis in 6 patients, and right axis in 1 patient. The tachycardia was electrically inducible and responsive to verapamil but not to adenosine. Thirteen patients demonstrated entrainment. Activation and pace-mapping studies disclosed that the tachycardia originated from the inferior apical septum in 15 patients, the midseptum in 4 patients, and the anterior lateral wall of the left ventricle in 1 patient. Radiofrequency ablation was successful in 17 of the 20 patients (85%). The successful ablation sites were characterized by an endocardial activation time 30 milliseconds earlier than the onset of QRS during tachycardia and by a pace-mapping QRS similar to or closely resembling the tachycardia. All patients displayed sharp spikes preceding the local ventricular electrogram at the ablation site. However, these sharp spikes also were noted in 15 control patients and were not specific for this tachycardia; they persisted after ablation. There were no complications. A follow-up of 7 +/- 8 months in the 17 successfully ablated patients showed no symptomatic tachyarrhythmias without medications. Six patients underwent repeat electrophysiological study, and no induction of tachycardia was revealed.

CONCLUSIONS
Radiofrequency ablation therapy is effective and safe in patients with idiopathic left ventricular tachycardia. It should be considered as the primary therapeutic modality in these patients.
Left ventricular mass and subsequent blood pressure changes among middle-aged men in rural and urban Japanese populations.
Authors: Iso H , Kiyama M , Doi M , Nakanishi N , Kitamura A , Naito Y , Sato S , Iida M , Konishi M , Shimamoto T 
Published: June 2012

BACKGROUND
It has been suggested that echocardiographically determined left ventricular mass (LVM) is useful in the prediction of hypertension. To examine the relation between LVM and subsequent blood pressure (BP) change, a 6- to 8-year follow-up was conducted in adult Japanese men.

METHODS AND RESULTS
LVM was determined by M-mode echocardiography using the American Society of Echocardiography formula among 354 normotensive men aged 30 to 59 years from a rural community (n = 193) and from urban companies (n = 161) in Japan between 1979 and 1983. BP was remeasured 6 to 8 years after baseline in 148 rural men (77%) and 127 urban men (79%). For men whose BP was remeasured, the mean +/- SD LVM index (LVM/body surface area [g/m2]) at baseline was 117 +/- 22 in rural men and 99 +/- 15 in urban men (the difference, P < .001). For both populations, LVM index was positively associated with age and physical activity but not with body mass index. Associations of LVM index with usual alcohol intake and initial BPs were generally weak. According to linear regression analyses after controlling for these covariates at baseline, a 20-g/m2 greater LVM index at baseline was associated with a 5 mm Hg increase in systolic and a 4 mm Hg increase in diastolic BP during the subsequent 6 to 8 years for urban men. A 1-mm greater average ventricular wall thickness was associated with a similar BP increase. For rural men, positive associations of LVM index with BP increase existed but were weak. The weaker association between LVM index and BP increase in rural compared with urban men was probably the result of effects of higher physical activity, leading to a larger left ventricular internal dimension. The increase in systolic and diastolic BPs over the 6 to 8 years of observation was significantly related to baseline LVM index in rural and urban men with a smaller internal dimension (rural men, < or = 49 mm; urban men, < or = 47 mm) but not in those with larger dimensions.

CONCLUSIONS
An increased LVM index predicts subsequent BP increase in middle-aged normotensive men in the presence of a normal or small internal dimension.
Biodegradable microspheres containing a colchicine analogue inhibit DNA synthesis in vascular smooth muscle cells.
Authors: March K L , Mohanraj S , Ho P P , Wilensky R L , Hathaway D R 
Published: June 2012

BACKGROUND
Smooth muscle cell proliferation plays a major role in the genesis of restenosis after angioplasty or vascular injury. Local application of agents capable of modulating vascular responses, including smooth muscle cell proliferation, has been achieved, but difficulty in maintaining active levels locally has been a factor limiting the efficacy of such approaches. One strategy to maintain adequate levels is the local delivery of microspheres that release active agents over sustained time periods.

METHODS AND RESULTS
We incorporated a colchicine analogue into biodegradable microspheres composed of a lactic acid/glycolic acid copolymer and characterized their drug release behavior as well as their effects on bovine aortic smooth muscle cells (BASMCs) in culture. Drug release was evaluated by spectrophotometric assay. Drug effects on DNA synthesis were measured by thymidine incorporation after addition of serum to subconfluent cells synchronized by serum withdrawal as well as in asynchronous cell populations. Polymeric microspheres incorporating 10% to 17% drug by weight and averaging 6 microns in size were found to release the colchicine analog in buffered saline solutions over more than several weeks. Drug-loaded particles inhibited DNA synthesis completely, with EC50 values ranging from 0.001 to 0.005 g% (wt/wt). Morphological changes suggesting microtubule depolymerization were observed after drug particle treatment, with similar EC50 values. Microspheres allowed to contact the cell surface demonstrated effects similar to those seen with microspheres suspended in the nutrient medium by porous polycarbonate filters, at EC50 values approximately fivefold lower. In contrast, control microspheres composed only of polymer with no incorporated active drug demonstrated no observable toxicity to BASMCs and < 40% inhibition of thymidine incorporation even in suspensions containing up to 0.5 g% particles.

CONCLUSIONS
Biodegradable microspheres were fashioned that release a colchicine analogue and inhibit DNA synthesis in smooth muscle cells. Drug-loaded polymeric particles are candidates for local delivery at sites of arterial injury to decrease restenosis.
Relation between coronary artery stenosis assessed by visual, caliper, and computer methods and exercise capacity in patients with single-vessel coronary artery disease. The Veterans Affairs ACME Investigators.
Authors: Folland E D , Vogel R A , Hartigan P , Bates E R , Beauman G J , Fortin T , Boucher C , Parisi A F 
Published: June 2012

BACKGROUND
Practitioners often assume a close relation between angiographic coronary artery stenosis and patient functional capacity. To test this unproven hypothesis, we analyzed the relation between coronary artery stenosis measured by different methods and maximal treadmill exercise tolerance in patients with single-vessel disease before and after intervention by percutaneous transluminal coronary angioplasty (PTCA).

METHODS AND RESULTS
Coronary angiography and maximal exercise testing off anti-ischemic medication were performed before random assignment of 227 patients with single-vessel coronary artery disease to PTCA or drug therapy. Six months later, angiography and exercise testing were repeated with patients assigned to PTCA off anti-ischemic therapy so that the altered coronary stenosis was the only consistent variable. Patients assigned to drug therapy were exercised on drug therapy. Coronary stenosis was assessed visually by the local investigator and quantitatively by blinded caliper and computer methods in central laboratories. Variabilities of caliper and computer measurements were established in a subset read twice. Visually estimated stenosis > or = 90% at baseline was associated with shorter exercise duration (7.9 versus 9.2 minutes, P < .04). Similar segregation at baseline was not observed with caliper or computer methods. Regardless of the method of measurement used, correlation between changes of lesion severity and exercise duration from baseline to follow-up was poor. Patients were angiographically classified as "better," "unchanged," or "worse" if follow-up stenosis was below, within, or above 2 SD of mean technical variability from baseline (+/- 18.8%, caliper, +/- 14.6%, computer). Exercise duration for PTCA patients improved among those with better lesions (+2.4 minutes, n = 50, P = .001) but also among those with unchanged lesions (+1.9 minutes, n = 41, P < or = .001). Unchanged medically treated patients improved less (+0.5 minutes, n = 86, P = .04). Results were similar when patients were angiographically classified by minimum lumen diameter.

CONCLUSIONS
Handheld calipers and quantitative coronary angiography are equivalent techniques for making anatomic measurements. Neither method identified patients having reduced exercise capacity at baseline as well as visual estimation. The relation between changes of coronary stenosis and exercise duration is highly variable, at least in part because of the insensitivity of angiographic methods for detecting small but potentially important changes. Minimal anatomic improvement 6 months after PTCA does not preclude a good functional outcome. Contrary to common belief, angiographic stenosis does not correlate well with functional capacity, even in patients with single-vessel disease.
Presence, evolving changes, and prognostic implications of myocardial damage detected in idiopathic and alcoholic dilated cardiomyopathy by 111In monoclonal antimyosin antibodies.
Authors: Obrador D , Ballester M , Carrió I , Moya C , Bosch I , Martí V , Bernà L , Estorch M , Udina C , Marrugat J 
Published: June 2012

BACKGROUND
The clinical relevance of myocardial cell damage in dilated cardiomyopathy is uncertain. Myocardial uptake of 111In monoclonal antimyosin antibodies (MAA) was used to study myocardial damage in patients with idiopathic (IDC) and alcoholic (ADC) dilated cardiomyopathy and to assess its prognostic implications.

METHODS AND RESULTS
MAA and echocardiographic studies were performed in 117 patients. Intensity of antibody uptake was measured by heart-to-lung ratio (HLR) (normal < 1.55). Studies were repeated in survivors and patients who did not receive a cardiac transplant. Follow-up extended up to 62 months (mean, 23 +/- 16 months). Eighty-eight patients with IDC showed a 77% prevalence of abnormal MAA. After acute-onset IDC, reduction of HLR (1.81 +/- 0.2 to 1.56 +/- 0.1) (P = .007) with improvement in ejection fraction (EF) (35 +/- 10% to 46 +/- 14%) (P = .018) was observed. No changes in HLR or EF were detected in patients with chronic stable IDC. Twenty-nine patients with ADC showed a lower prevalence (48%) of abnormal MAA studies than those with IDC (P = .003). HLR was higher in 13 active (1.78 +/- 0.3) than in 16 past consumers (1.49 +/- 0.2) (P = .019); in the former, HLR decreased to 1.44 +/- 0.2 (P = .012), and EF improved (35 +/- 14% to 53 +/- 18%) (P = .05) after abstention. Intensities of uptake HLR of > 1.87 were associated with increased risk of death or transplantation.

CONCLUSIONS
In patients with IDC, variations of MAA uptake are detected in patients who present acutely but not in those with chronic stable disease. In patients with ADC, MAA uptake mainly depends on alcohol consumption. In both situations, reduction of uptake correlates with improvement of ventricular function. Higher intensities of MAA uptake are associated with a worse outcome. The intensity of antibody uptake, along with other clinical and functional variables, may be helpful in risk stratification of patients with dilated cardiomyopathy.
Mechanisms of entrainment of human common flutter studied with multiple endocardial recordings.
Authors: Cosío F G , López Gil M , Arribas F , Palacios J , Goicolea A , Núñez A 
Published: June 2012

BACKGROUND
The mechanisms of common atrial flutter entrainment have not been directly studied in humans.

METHODS AND RESULTS
Endocardial mapping in six cases of common flutter showed large right atrial (RA) reentry circuits. Activation was craniocaudal in the anterolateral right atrium and caudocranial in the septum. The inferior vena cava-tricuspid isthmus (IVC-TV) closed the circuit. The high right atrium was paced at progressively shorter cycle lengths (CLs) in all, and the IVC-TV was paced in three cases. We recorded six to eight simultaneous RA electrograms from septum and anterior wall. Transient entrainment was recognized from all sites by capture of all electrograms at two or more paced CLs, with total or partial preservation of baseline flutter sequence and return to baseline after pacing. Antidromic circuit penetration was documented in five cases during high RA pacing and in one with IVC-TV pacing. Short CLs induced orthodromic conduction delays that resulted in a postpacing pause longer than basal flutter CL. ECG fusion with high RA pacing correlated poorly with antidromic septal penetration. This was related to overlap of orthodromic septal activation with anterior wall activation of the following cycle. Pacing disorganized flutter into a brief irregular rapid rhythm in two cases and atrial fibrillation in one case. In two cases, complete antidromic septal penetration led to sudden flutter interruption, and in another case it led to circuit inversion.

CONCLUSIONS
Direct recordings confirm orthodromic and antidromic penetration of flutter circuits by high and low RA pacing. Short CLs modify the circuit. Disorganization is the most common mode of flutter interruption.
T-cell receptor V beta gene expression in infiltrating cells in murine hearts with acute myocarditis caused by coxsackievirus B3.
Authors: Seko Y , Yagita H , Okumura K , Yazaki Y 
Published: June 2012

BACKGROUND
In viral myocarditis, we previously reported that natural killer cells infiltrate the heart first, then activated T cells infiltrate second and play an important role in the pathogenesis of the myocardial damage.

METHODS AND RESULTS
To elucidate the nature of T-cell infiltration, using a murine model of acute myocarditis caused by coxsackievirus B3, we analyzed the expression of T-cell receptor (TCR) V beta genes in infiltrating cells in the heart by polymerase chain reaction (PCR). The PCR-amplified products were confirmed by Southern blot hybridization with a C beta cDNA probe. In contrast to spleen lymphocytes, the repertoire of V beta gene transcripts in the heart was restricted. The infiltrating cells expressing V beta 10 were found in six of eight hearts of mice with acute myocarditis. The infiltrating cells expressing V beta 8 and V beta 13 were found in four of eight hearts with myocarditis, respectively. Immunoperoxidase staining of serial sections of the heart of myocarditis for TCR alpha beta chains and TCR V beta 10 confirmed that the dominant population of infiltrating T cells expressed V beta 10 gene products.

CONCLUSIONS
The restricted usage of TCR genes by infiltrating T-cells may indicate that a specific antigen in heart with myocarditis is targeted. Our findings raise the possibility of immunotherapy with monoclonal antibodies specific for TCR V beta elements to prevent T-cell-mediated myocardial damage in viral myocarditis.