bluuebunny/crossref_metadata_2025_split huggingface dataset:
Possibility of downregulation of atrial natriuretic peptide receptor coupled to guanylate cyclase in peripheral vascular beds of patients with chronic severe heart failure.
Authors: Tsutamoto T , Kanamori T , Morigami N , Sugimoto Y , Yamaoka O , Kinoshita M 
Published: June 2012

BACKGROUND
High levels of endogenous atrial natriuretic peptide (ANP) are thought to compensate the condition of patients with heart failure by reducing preload and afterload. However, recent reports have indicated that a high plasma ANP level is a prognostic predictor in patients with heart failure. Therefore, the role of endogenous ANP has not been clearly established in patients with heart failure.

METHODS AND RESULTS
The plasma ANP and cGMP levels were determined in the femoral artery and the femoral vein of 97 patients with chronic congestive heart failure (CHF). The plasma ANP level decreased significantly, whereas the plasma cGMP levels increased significantly from the femoral artery to the femoral vein. Among patients with mild CHF (n = 52), the plasma cGMP level correlated with the ANP level, and the calculated ANP extraction level also correlated with the calculated cGMP production in the peripheral circulation (r = 0.70, p < 0.001). In contrast, these correlations were not found in patients with severe CHF (n = 45). Among these patients, the plasma cGMP levels seemed to reach a plateau despite high levels of plasma ANP, and the molar ratio of cGMP production to ANP extraction in the peripheral circulation was significantly lower than in patients with mild CHF (36.7 +/- 9.5 versus 183 +/- 17, p < 0.001). In patients with acute severe CHF (n = 9) and those with mild CHF, patients who were administered exogenous ANP, plasma cGMP levels increased in proportion to those of plasma ANP without saturation.

CONCLUSIONS
These results indicate that downregulation of ANP receptors coupled to guanylate cyclase may occur in the peripheral vascular beds of patients with chronic severe CHF.
Long-term benefit of 1-year amiodarone treatment for persistent complex ventricular arrhythmias after myocardial infarction.
Authors: Pfisterer M E , Kiowski W , Brunner H , Burckhardt D , Burkart F 
Published: June 2012

BACKGROUND
In the Basel Antiarrhythmic Study of Infarct Survival trial, low-dose amiodarone improved 1-year survival in patients with asymptomatic complex ventricular arrhythmias persisting 2 weeks after myocardial infarction. To assess whether this beneficial effect persisted despite discontinuation of amiodarone after 1 year, the long-term outcomes of all patients of the amiodarone-treated group (initially n = 98) and those of the control group (n = 114) were assessed.

METHODS AND RESULTS
After a mean follow-up of 72 (55-125) months, information on 96% of patients (203 of 212) was obtained regarding survival or cause of death. The probability of death after 84 months according to actuarial life-table analysis (Kaplan-Meier) was 30% for the amiodarone-treated patients and 45% for control patients. For the total follow-up, mortality remained significantly lower in the amiodarone group versus the control group regarding all deaths (p = 0.03) as well as cardiac death (p = 0.047). This mortality reduction was entirely due to the first-year amiodarone effect, since there was no significant mortality difference between groups when considering survival after discontinuation of amiodarone only.

CONCLUSIONS
These data suggest that the beneficial effect of amiodarone on survival in this high-risk group of patients persists for several years. In addition, the results stress the importance of early treatment after myocardial infarction, whereas the rate of sudden death and all cardiac death is low (1.6% and 4.1% per year, respectively) during late follow-up and therefore may not warrant further therapy.
Selection of the optimal nonexercise stress for the evaluation of ischemic regional myocardial dysfunction and malperfusion. Comparison of dobutamine and adenosine using echocardiography and 99mTc-MIBI single photon emission computed tomography.
Authors: Marwick T , Willemart B , D'Hondt A M , Baudhuin T , Wijns W , Detry J M , Melin J 
Published: June 2012

BACKGROUND
The mechanisms of action of exercise-simulating and vasodilator stressors support their combination with imaging techniques that evaluate left ventricular function and perfusion, respectively. However, reported accuracies of either pharmacological stress together with two-dimensional echocardiography (2DE) or single photon emission computed tomography (SPECT) of myocardial perfusion are similar. The purpose of this study was to establish the optimal stress for each imaging technique by comparing the results of digitized 2DE and 99mTc-methoxyisobutyl isonitrile (MIBI) SPECT using both dobutamine and adenosine stresses in the same patients and conditions.

METHODS AND RESULTS
Ninety-seven consecutive patients without evidence of previous infarction undergoing coronary angiography for clinical indications were studied prospectively. Dobutamine was infused during clinical, ECG, and echocardiographic monitoring in dose increments from 5 to 40 micrograms.kg-1.min-1. Adenosine was infused under the same conditions in doses of 0.10, 0.14, and 0.18 mg.kg-1.min-1. For each protocol, the end points were achievement of peak dose, development of severe ischemia, or intolerable side effects. At peak stress, 20 mCi of MIBI was injected, and SPECT imaging was performed 2 hours later; abnormal poststress images were compared with resting SPECT: Digitized 2DE images were compared qualitatively before, during, and after stress in a cine-loop display. Significant coronary disease (n = 59 patients) was defined by the quantification of > 50% stenosis in a major epicardial vessel. The sensitivity of adenosine 2DE was 58%, less than those of adenosine MIBI (86%, p = 0.001), dobutamine 2DE (85%, p = 0.001), and dobutamine MIBI (80%, p = 0.01). Their respective specificities were 87%, 71%, 82%, and 74% (p = NS). The accuracy of adenosine 2DE was 69%, compared with 80% for adenosine MIBI (p < 0.001), 84% for dobutamine 2DE (p = 0.001), and 77% for dobutamine MIBI (p = 0.005); the latter three did not differ significantly in either sensitivity or accuracy.

CONCLUSIONS
This prospective, direct comparison of alternative pharmacological stresses in patients without myocardial infarction shows vasodilator stress scintigraphy and dobutamine stress echocardiography and scintigraphy to share equivalent levels of sensitivity. All three are significantly more sensitive than adenosine stress echocardiography. Dobutamine stress may be used for wall motion or perfusion imaging, but adenosine stress is best combined with perfusion scintigraphy.
Hypertrophic cardiomyopathy mutation is expressed in messenger RNA of skeletal as well as cardiac muscle.
Authors: Yu Q T , Ifegwu J , Marian A J , Mares A , Hill R , Perryman M B , Bachinski L L , Roberts R , Marlan A J 
Published: June 2012

BACKGROUND
The beta-myosin heavy chain (beta-MHC) gene has been identified as a major locus for familial hypertrophic cardiomyopathy (FHCM). We recently showed that one of the common mutations associated with FHCM is expressed in the cardiac muscle messenger RNA (mRNA) of an affected individual. Since beta-MHC is a major sarcomeric protein of cardiac and skeletal muscle, studies were performed to determine whether the mutation is also expressed in skeletal muscle.

METHODS AND RESULTS
Biopsies were obtained of skeletal muscle (biceps brachii) from a proband with FHCM known to have the missense mutation in exon 13 of the beta-MHC gene. RNA was extracted from skeletal muscle and lymphocytes by the RNAzol method. First-strand complementary DNA was synthesized by reverse transcription using an antisense primer to exon 16. Polymerase chain reaction (PCR) was performed using primers to exons 12 and 14 to amplify the segment encompassing exon 13. The PCR products were digested with Ddel restriction endonuclease. Undigested PCR product in the control and the proband was 321 base-pairs (bp). Ddel digestion of the PCR product from normal skeletal and lymphocytes showed two DNA fragments of 181 and 140 bp as expected, whereas digestion of the PCR product from the proband's skeletal muscle and lymphocytes showed four DNA fragments of 181, 149, 140, and 32 bp due to the mutation in exon 13. This indicates that the mutation in affected individuals is also expressed in the mRNA of skeletal muscle and lymphocytes.

CONCLUSIONS
To our knowledge, this is the first documentation of a beta-MHC gene mutation expressed in skeletal muscle. This finding is provocative. Does it impair skeletal muscle function? If so, how? If not, why not? Is the impairment, or lack of it, a clue to the molecular defect of cardiac muscle? Furthermore, skeletal muscle provides a readily accessible source of mRNA for expression studies and for purification of the beta-MHC protein, which is probably essential to future investigation designed to unravel the molecular basis of this disorder.
Uncoupling of human cardiac beta-adrenoceptors during cardiopulmonary bypass with cardioplegic cardiac arrest.
Authors: Schranz D , Droege A , Broede A , Brodermann G , Schäfer E , Oelert H , Brodde O E 
Published: June 2012

BACKGROUND
It is well known that during cardiopulmonary bypass (CPB) with cardioplegic cardiac arrest, catecholamines are vigorously increased. We therefore investigated whether this might cause desensitization of human cardiac beta-adrenoceptors.

METHODS AND RESULTS
We assessed in 12 children with acyanotic congenital heart disease who underwent open-heart surgery right atrial beta-adrenoceptor number and subtype distribution [by (-)-[125I]iodocyanopindolol binding] and adenylate cyclase activation [by the beta-adrenoceptor agonist isoprenaline (100 microM) and by the non-receptor-mediated activators 10 microM GTP, 10 mM NaF, 100 microM forskolin, and 10 mM Mn2+] before and after CPB with cardiac arrest by means of St. Thomas' cardioplegic solution. CPB affected neither beta-adrenoceptor number of subtype distribution nor GTP-, NaF-, forskolin-, or Mn(2+)-induced activation of adenylate cyclase. In contrast, activation of adenylate cyclase by 100 microM isoprenaline was significantly (p = 0.0249) lower after CPB than before CPB.

CONCLUSIONS
CPB with cardioplegic cardiac arrest decreases beta-adrenoceptor-mediated adenylate cyclase activation in a manner compatible with an uncoupling of beta-adrenoceptors from the Gs-protein-adenylate cyclase complex. Such a beta-adrenoceptor desensitization may be the reason why after CPB many patients need inotropic support but do not respond sufficiently to catecholamines.
Different secretion patterns of atrial natriuretic peptide and brain natriuretic peptide in patients with congestive heart failure.
Authors: Yoshimura M , Yasue H , Okumura K , Ogawa H , Jougasaki M , Mukoyama M , Nakao K , Imura H 
Published: June 2012

BACKGROUND
The plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are increased in relation to the severity of congestive heart failure (CHF). This study was designed to examine whether the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.

METHODS AND RESULTS
We measured plasma levels of ANP and BNP in the aorta in 20 patients with mitral stenosis (MS) in whom atria are mainly overloaded, 30 patients with dilated cardiomyopathy (DCM) in whom both atria and ventricles are overloaded, and 20 control subjects during cardiac catheterization. Pulmonary capillary wedge pressure (PCWP) was significantly higher in the MS and DCM groups (16.7 +/- 4.7 mm Hg and 15.1 +/- 7.7 mm Hg, respectively) than in the control group (7.2 +/- 1.1 mm Hg, p < 0.01), whereas there was no significant difference between the MS and DCM groups. Left ventricular end-diastolic pressure (LVEDP) was significantly higher in the DCM group than in the MS group (16.4 +/- 7.8 mm Hg versus 7.6 +/- 2.0 mm Hg, p < 0.01), and the level was comparable between the MS and control groups (7.6 +/- 2.0 mm Hg versus 6.8 +/- 1.2 mm Hg, p = NS). The plasma ANP level was significantly higher in the MS and DCM groups (356 +/- 169 pg/ml and 331 +/- 323 pg/ml, respectively) than in the control group (98 +/- 41 pg/ml, p < 0.01), whereas there was no significant difference between the MS and DCM groups. The plasma BNP level was significantly higher in the DCM group than in the MS group (333 +/- 405 pg/ml versus 147 +/- 54 pg/ml, p < 0.01), and the level was significantly higher in the MS group than in the control group (147 +/- 54 pg/ml versus < 10 pg/ml, p < 0.01). The plasma levels of ANP and BNP had a highly positive correlation with PCWP in the DCM group (p < 0.01). On the other hand, in the MS group, the plasma ANP level had a highly significant correlation with PCWP (p < 0.01) but the plasma BNP level did not.

CONCLUSIONS
We conclude that plasma levels of BNP mainly reflect the degree of ventricular overload and that the secretion patterns of ANP and BNP vary with underlying cardiac disorders of CHF with different degrees of overload in atria and ventricles.
Exertional fatigue due to skeletal muscle dysfunction in patients with heart failure.
Authors: Wilson J R , Mancini D M , Dunkman W B 
Published: June 2012

BACKGROUND
Exertional fatigue in patients with chronic heart failure is usually attributed to skeletal muscle underperfusion. Recently, skeletal muscle atrophy, abnormal muscle metabolic responses, and reduced muscle enzyme levels have been noted in such patients, raising the possibility that some patients may develop muscle fatigue due to intrinsic muscle abnormalities. The present study was undertaken to determine if a subpopulation of patients with heart failure develops exertional fatigue due to skeletal muscle dysfunction rather than to reduced muscle flow.

METHODS AND RESULTS
All exercise hemodynamic studies performed in our laboratory on patients with heart failure were reviewed to identify those who exhibited peak exercise VO2 levels < or = 18 ml.min-1 x kg-1 due to leg fatigue and who underwent insertion of a Swan-Ganz catheter and leg blood flow catheter. Thirty-four patients were identified. Six normal subjects were also studied to define normal leg flow and femoral venous lactate responses to exercise. Patients with peak exercise leg flow levels within the normal mean flow level +/- 2 SEM were considered to have normal skeletal muscle flow during exercise. Nine of the 34 patients with heart failure were found to have normal leg blood flow during exercise. All of these patients terminated exercise due to leg fatigue, and all exhibited abnormal increases in femoral venous lactate concentrations (slope of work load versus femoral venous lactate: normal, 0.33 +/- 0.07 mg/W; heart failure with normal flow, 0.81 +/- 0.08 mg/W; p < 0.002). There was no significant difference between patients with normal leg flows and those with reduced flow in age, ejection fraction, and resting hemodynamic measurements. However, patients with normal flows exhibited more normal cardiac output responses to exercise and tended to have higher peak exercise VO2 (14.1 +/- 0.9 versus 11.5 +/- 0.7 ml.min-1 x kg-1, p < 0.05).

CONCLUSIONS
A substantial percentage of patients with chronic heart failure develop exertional fatigue due to skeletal muscle dysfunction rather than to reduced skeletal muscle blood flow. In such patients, therapeutic interventions probably should be directed at improving the skeletal muscle abnormalities rather than at improving skeletal muscle flow.
Radiofrequency endocardial catheter ablation of accessory atrioventricular pathway atrial insertion sites.
Authors: Swartz J F , Tracy C M , Fletcher R D 
Published: June 2012

BACKGROUND
High rates of success using radiofrequency ablation energy have rapidly transformed catheter ablation from an investigational procedure to the nonpharmacological therapy of choice for symptomatic Wolff-Parkinson-White syndrome. Prior studies of radiofrequency accessory pathway ablation were based on a ventricular approach. Risks associated with prolonged arterial catheter manipulation, retrograde left ventricular catheterization, and production of ventricular lesions required for successful ventricular insertion ablation can be avoided using atrial insertion ablation procedures. The purpose of the present study was to define the safety and efficacy of accessory pathway ablation using radiofrequency energy delivered solely to accessory atrioventricular pathway atrial insertion sites.

METHODS AND RESULTS
One hundred fourteen patients with accessory pathway-mediated tachycardia underwent attempted radiofrequency current ablation at the accessory pathway atrial insertion site. All catheters were introduced transvenously. Left-sided accessory pathways were approached using transseptal left atrial catheterization techniques. Retrograde localization of the atrial insertion site during reentrant tachycardia was characterized by 40 +/- 15-msec local ventriculoatrial and 79 +/- 17-msec surface QRS to local atrial electrogram intervals. Presumed accessory pathway potentials were present in only 30% of ablation site electrograms. Successful ablation required 6.2 +/- 5.3 radiofrequency energy applications. Cumulative energy dose required for success was 2,341 +/- 2,233 J. There were no complications associated with transseptal catheterization. Energy delivery to accessory pathway atrial insertion sites was associated with non-life-threatening complications in two patients. Recurrent conduction requiring repeat ablation occurred in 10 of 115 (9%) successfully ablated accessory pathways, all within 1 month of the ablation procedure. After 21.2 +/- 4.6 months of follow-up, 108 of 114 (95%) patients are asymptomatic and without evidence of accessory pathway conduction.

CONCLUSIONS
The atrial insertion approach to accessory pathway ablation is safe and highly effective. This approach compares favorably with the retrograde ventricular insertion ablation technique. Atrial insertion ablation eliminates the need to produce ventricular lesions and avoids the risks of prolonged arterial catheter manipulation and retrograde left ventricular catheterization.
Acute effects of nitroglycerin depend on both plasma and intracellular sulfhydryl compound levels in vivo. Effect of agents with different sulfhydryl-modulating properties.
Authors: Boesgaard S , Poulsen H E , Aldershvile J , Loft S , Anderson M E , Meister A 
Published: June 2012

BACKGROUND
Changes in sulfhydryl (SH) compound availability may alter the hemodynamic effect of nitroglycerin (NTG). Data on the relation between NTG effect and thiol levels are, however, limited to in vitro experiments. The present study investigates how intracellular and extracellular changes in SH group concentrations (cysteine and glutathione [GSH]) affect the responsiveness to NTG in vivo.

METHODS AND RESULTS
GSH and cysteine levels in plasma, vena cava, and aorta were measured after administration of N-acetylserine (placebo, n = 6), N-acetylcysteine (NAC, extracellular and intracellular SH donor, n = 6), oxothiazolidine (OXO, intracellular SH donor, n = 6), buthionine sulfoximine (BSO, intracellular GSH-depleting agent, n = 6), BSO+NAC (n = 6), and BSO+OXO (n = 6) in chronically catheterized conscious rats. In addition, the effect of 2.5 mg NTG/kg i.v. on mean arterial pressure (MAP) was determined before and after the same treatment. NAC (5 mmol/kg i.v. for 2 hours) significantly (p < 0.05) increased extracellular cysteine and GSH levels and potentiated the hypotensive effect of NTG (from 26 +/- 3 to 31 +/- 4 mm Hg [mean +/- SEM], p < 0.05). OXO (5 mmol.kg-1 x hr-1 i.v. for 2 hours) significantly increased intracellular cysteine and GSH levels but had no effect on NTG responsiveness (p > 0.05). BSO (1 g i.p. three times within 24 hours) significantly decreased intracellular GSH levels (p < 0.05) and attenuated the effect of NTG (from 28 +/- 3 to 16 +/- 2 mm Hg).

CONCLUSIONS
The results suggest that the acute hypotensive effect of NTG in vivo is: 1) increased by high extracellular GSH and/or cysteine levels (NAC), 2) decreased by low intracellular GSH levels (BSO), and 3) unaffected by high intracellular levels of cysteine and GSH (OXO).
Role of endogenous atrial natriuretic peptide in DOCA-salt hypertensive rats. Effects of a novel nonpeptide antagonist for atrial natriuretic peptide receptor.
Authors: Hirata Y , Matsuoka H , Suzuki E , Hayakawa H , Sugimoto T , Matsuda Y , Morishita Y , Kangawa K , Minamino N , Matsuo H 
Published: June 2012

BACKGROUND
To explore roles of endogenous atrial natriuretic peptide (ANP) in blood pressure and volume regulation, we examined the effects of a newly developed ANP antagonist, HS-142-1 (HS) in deoxycorticosterone acetate (DOCA)-salt hypertensive rats.

METHODS AND RESULTS
We examined 1) the effects of HS on ANP- or brain natriuretic peptide (BNP)-induced reductions in renal vascular resistance (RVR) of rat isolated perfused kidneys, 2) the effects of HS on cyclic GMP (cGMP) production in rat cultured vascular smooth muscle cells pretreated with ANP or BNP, and 3) the renal and systemic effects of HS in DOCA-salt-treated rats and control rats. We found that 1) HS dose-dependently reversed ANP- or BNP-induced decreases in RVR; 2) ANP or BNP at 100 nM caused an eightfold increase in cGMP production. These increases in cGMP were inhibited by HS in a dose-dependent fashion, and 300 micrograms/ml HS decreased cGMP to the control level. HS alone did not influence RVR or cGMP production; and 3) DOCA-salt rats showed higher plasma concentrations of ANP (198 versus 75 pg/ml) and BNP (23.7 versus 2.7 pg/ml, each p < 0.01) than the control rats. Bolus administration of 8 mg/kg HS elevated blood pressure by 8% (p < 0.01). This rise in blood pressure was attributed to an increase in systemic vascular resistance (+14%, p < 0.05). Conversely, urinary excretion of sodium (-41%), glomerular filtration rate (-27%), and plasma (-77%) and urinary cGMP (-69%, each p < 0.01) were decreased by administration of 8 mg/kg HS. These effects were dose dependent in DOCA-salt rats but slight or negligible in the control rats.

CONCLUSIONS
These results suggest that endogenous ANP and BNP may be involved in the regulation of blood pressure and body fluid volume in DOCA-salt rats in which ANP and BNP secretion is augmented.