bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiac troponin I. A marker with high specificity for cardiac injury.
Authors: Adams J E , Bodor G S , Dávila-Román V G , Delmez J A , Apple F S , Ladenson J H , Jaffe A S 
Published: June 2012

BACKGROUND
Levels of MBCK can be increased in patients with skeletal muscle injury or renal failure in the absence of myocardial injury, causing diagnostic confusion. This study was designed to determine whether measurement of cardiac troponin I (cTnI), a myocardial regulatory protein with comparable sensitivity to MBCK, has sufficient specificity to clarify the etiology of MBCK elevations in patients with acute or chronic skeletal muscle disease or renal failure.

METHODS AND RESULTS
Of the patients (n = 215) studied, 37 had acute skeletal muscle injury, 10 had chronic muscle disease, nine were marathon runners, and 159 were chronic dialysis patients. Patients were evaluated clinically, by ECG, and by two-dimensional echocardiography. Total creatine kinase (normal, < 170 IU/L) was determined spectrophotometrically, and cTnI (normal, < 3.1 ng/mL) and MBCK (normal, < 6.7 ng/mL) were determined with specific monoclonal antibodies. Values above the upper reference limit were considered "elevated." Elevations of total creatine kinase were common, and elevations of MBCK occurred in 59% of patients with acute muscle injury, 78% of patients with chronic muscle disease and marathon runners, and 3.8% of patients with chronic renal failure. Some of the patients were critically ill; five patients were found to have had myocardial infarctions and one had a myocardial contusion. cTnI was elevated only in these patients.

CONCLUSIONS
Elevations of cTnI are highly specific for myocardial injury. Use of cTnI should facilitate distinguishing whether elevations of MBCK are due to myocardial or skeletal muscle injury.
Prognostic value and physiological correlates of heart rate variability in chronic severe mitral regurgitation.
Authors: Stein K M , Borer J S , Hochreiter C , Okin P M , Herrold E M , Devereux R B , Kligfield P 
Published: June 2012

BACKGROUND
A variety of measures of heart rate variability have been devised to measure high-frequency (0.15-0.40 Hz), low-frequency (0.04-0.15 Hz), or ultralow-frequency (< 0.0033 Hz) fluctuations in sinus cycle length. Although measures of low-frequency and ultralow-frequency heart rate variability have been shown to correlate with prognosis in several populations with ischemic heart disease, their relevance to patients with primary valvular heart disease remains to be determined.

METHODS AND RESULTS
Thirty-eight patients with nonischemic causes of chronic severe mitral regurgitation who were in sinus rhythm underwent 24-hour ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular heart disease. Patients were followed for as long as 9.2 years, and end points of mortality, progression to mitral valve surgery, and development of chronic atrial fibrillation were tabulated. Time- and frequency-domain measurements of high-frequency, low-frequency, and ultralow-frequency heart rate variability were computed and compared with resting ventricular function by radionuclide cineangiography and outcome. The standard deviation of the 5-minute mean RR intervals (SDANN), a measure of ultralow-frequency heart rate variability, was correlated with left ventricular ejection fraction (r = 0.49, p = 0.002) and right ventricular ejection fraction (r = 0.43, p = 0.007), whereas low-frequency and high-frequency heart rate variabilities were not. Heart rate, ultralow-frequency heart rate variability, and, to a lesser extent, high-frequency heart rate variability exhibited significant diurnal variation, but low-frequency heart rate variability did not. Heart rate and ultralow-frequency, low-frequency, and combined low- and high-frequency heart rate variability predicted mortality and total events. The most powerful predictor of subsequent events was SDANN: Patients with reduced SDANN were significantly more likely to develop end-point events (p < 0.001) with increased progression to mitral valve surgery (p < 0.001) as well as increased early mortality (p = 0.02). In a multivariate proportional hazards model, SDANN retained independent predictive power (p = 0.001). Likewise, SDANN was the only variable that was significantly associated with the subsequent development of atrial fibrillation (relative risk, 3.1; p = 0.03).

CONCLUSIONS
Ultralow-frequency heart rate variability, as measured by SDANN, correlates with right and left ventricular performance and predicts development of atrial fibrillation, mortality, and progression to valve surgery in patients with chronic severe mitral regurgitation.
Cardiac sympathetic nervous activity in congestive heart failure. Evidence for increased neuronal norepinephrine release and preserved neuronal uptake.
Authors: Meredith I T , Eisenhofer G , Lambert G W , Dewar E M , Jennings G L , Esler M D 
Published: June 2012

BACKGROUND
Increased concentrations of norepinephrine in coronary sinus plasma reported in congestive heart failure (CHF) could result from increased cardiac sympathetic nerve firing and norepinephrine release or from failure of neuronal uptake mechanisms to recapture released norepinephrine. We have applied neurochemical indexes of cardiac sympathetic nerve function in heart failure patients to delineate the underlying neural pathophysiology.

METHODS AND RESULTS
Cardiac norepinephrine synthesis, assessed from the cardiac overflow of the norepinephrine precursor dihydroxyphenylalanine (DOPA), intraneuronal metabolism estimated from the overflow of the intraneuronal metabolite dihydroxyphenylglycol (DHPG), neuronal norepinephrine reuptake assessed from the fractional extraction of plasma-tritiated norepinephrine and production of tritiated DHPG across the heart, and norepinephrine spillover to plasma were examined in eight patients with CHF caused by coronary artery disease (left ventricular ejection fraction of 26 +/- 5%, mean +/- SEM) and 14 age-matched healthy subjects. Cardiac norepinephrine spillover was increased eightfold in CHF subjects (127 ng/min versus 14 ng/min in healthy subjects; standard error of the difference [SED], 8 ng/min; P < .002), and cardiac DOPA was increased twofold (P < .02). The fractional extraction of tritiated norepinephrine across the heart was marginally less in CHF subjects (0.63 versus 0.73 in normal subjects; SED, 0.02), but the extent to which pharmacological neuronal uptake blockade with desipramine reduced the cardiac extraction of tritiated norepinephrine (by 71% versus 73% in normal subjects) and reduced the production of tritiated DHPG derived from uptake and intraneuronal metabolism of tritiated norepinephrine was similar in CHF patients and healthy subjects.

CONCLUSIONS
The marked increase in norepinephrine spillover from the heart in CHF attributable to coronary artery disease results primarily from an increase in sympathetic nerve firing and neuronal release of norepinephrine, not from faulty neuronal reuptake of norepinephrine.
Regional differences in sympathetic reinnervation after human orthotopic cardiac transplantation.
Authors: Wilson R F , Laxson D D , Christensen B V , McGinn A L , Kubo S H 
Published: June 2012

BACKGROUND
In the majority of humans > or = 1 year after cardiac transplantation, cardiac norepinephrine (NE) stores reappear, suggesting late sympathetic reinnervation.

METHODS AND RESULTS
To determine whether there are regional differences in reinnervation, we measured markers of sympathetic reinnervation of the sinus node (SN) and left ventricle (LV) in five early transplant recipients (< or = 4 months after cardiac transplantation), 45 late transplant recipients (> or = 1 year after cardiac transplantation), and seven normally innervated control patients. SN reinnervation was defined as an increase in heart rate by more than five beats per minute after injection of tyramine into the artery supplying the SN. LV reinnervation was defined as a measurable LV NE release after left main coronary injection of 8 micrograms/kg tyramine. In 13 patients with previously known LV reinnervation, regional LV reinnervation was assessed by NE release after subselective injection of tyramine (4 micrograms/kg) into the proximal left anterior descending and circumflex arteries. Five of five patients < or = 4 months after cardiac transplantation had no change in heart rate and no LV NE release, confirming early, total denervation. In contrast, > or = 1 year after cardiac transplantation, tyramine caused a heart rate increase (eight to 49 beats per minute) in 32 of 45 patients and LV NE release in 33 of 45. Although LV NE release was correlated with the change in heart rate in late cardiac transplantation recipients (r = .61), eight of 45 had only heart rate response, nine had only LV NE release, and four had neither. In late cardiac transplantation recipients with LV reinnervation, tyramine caused NE release from both the anterior descending and circumflex perfusion fields in 10 of 14, but one of 14 patients released NE only after circumflex tyramine and three of 14 only after left anterior descending tyramine stimulation. Tyramine caused a marked heart rate increase and LV NE release in all control patients.

CONCLUSIONS
Sympathetic reinnervation after cardiac transplantation is regionally heterogeneous. SN reinnervation is not associated necessarily with LV reinnervation, and LV reinnervation can involve the anterior and posterior walls together or separately.
Temperature-guided radiofrequency catheter ablation with very large distal electrodes.
Authors: Langberg J J , Gallagher M , Strickberger S A , Amirana O 
Published: June 2012

BACKGROUND
Previous studies have shown that the size of lesions produced by radiofrequency catheter ablation correlates with the temperature and surface area of the electrode-tissue interface. The purpose of the present study was to compare the effects of ablation using very large distal electrodes (8F, 8 and 12 mm long) with those made by a conventional radiofrequency ablation catheter (distal electrode 8F, 4 mm long).

METHODS AND RESULTS
Each catheter had a thermistor in the tip of the distal electrode. Radiofrequency energy (500 kHz) was supplied by a generator that continuously monitored temperature and produced up to 100 W. In 10 dogs, each of the three ablation catheters were introduced percutaneously and positioned under fluoroscopic guidance at disparate left ventricular endocardial sites. Radiofrequency power output was titrated to achieve a temperature of 80 degrees C for 60 seconds at each ablation site. The power required to produce a steady-state temperature of 80 degrees C was directly proportional to electrode size (15 +/- 7, 46 +/- 15, and 62 +/- 32 W using the 4-mm-, 8-mm-, and 12-mm-long electrodes, respectively). Lesions produced by the 8-mm electrode were nearly twice as deep (11 +/- 2.4 versus 6 +/- 1.2 mm, P < .001) and four times as large (905 +/- 410 versus 210 +/- 100 mm3, P < .001) as those made with a conventional 4-mm electrode. Lesions produced by the 12-mm electrode were intermediate in size (depth, 8 +/- 1.2 mm; volume, 465 +/- 225 mm3) and sometimes were associated with charring and crater formation. Ablation with the larger electrodes caused a drop in arterial pressure and more ventricular ectopy than ablation using a 4-mm distal electrode.

CONCLUSIONS
Thermistor-equipped elongated ablation electrodes coupled to high-power outputs can reproducibly produce lesions approximately 1 cm in diameter. This system may prove useful for ablation of ventricular tachycardias in patients with coronary artery disease.
Effects of age on endothelium-dependent vasodilation of resistance coronary artery by acetylcholine in humans.
Authors: Egashira K , Inou T , Hirooka Y , Kai H , Sugimachi M , Suzuki S , Kuga T , Urabe Y , Takeshita A 
Published: June 2012

BACKGROUND
It has been suggested that endothelium-related vasomotion is important in the control of coronary circulation. Our goal was to determine if endothelium-dependent dilation of the coronary vasculature was altered with aging in 18 patients with atypical chest pain (age, 23-70 years) who had angiographically normal coronary arteries and no coronary risk factors.

METHODS AND RESULTS
We infused an endothelium-dependent vasodilator acetylcholine (1, 3, 10, and 30 micrograms/min) and an endothelium-independent vasodilator papaverine (10 mg) into the left coronary artery. The large coronary diameter was assessed by arteriography, and the increase in coronary blood flow was measured using the intracoronary Doppler catheter technique. Acetylcholine increased coronary blood flow in a dose-dependent manner with no changes in arterial pressure and heart rate. The maximum increase in coronary blood flow evoked by acetylcholine varied widely among patients (increase in coronary blood flow ranged from 200% to 560%) and was correlated significantly with aging (r = -.86, P < .001), whereas the peak coronary blood flow response to papaverine was affected slightly by aging (r = -.44, P = .07). The percent increase in blood flow response to acetylcholine to the response to papaverine correlated with aging (r = -.87, P < .001). The slope of the coronary blood flow response to acetylcholine also correlated significantly with aging. The large epicardial coronary artery response to the low doses of acetylcholine (< or = 10 micrograms/min) correlated inversely with aging.

CONCLUSIONS
The results of this study suggest that endothelium-dependent dilation of coronary arteries evoked by acetylcholine may be decreased with aging in humans.
Increased plasma levels of brain natriuretic peptide in patients with acute myocardial infarction.
Authors: Morita E , Yasue H , Yoshimura M , Ogawa H , Jougasaki M , Matsumura T , Mukoyama M , Nakao K 
Published: June 2012

BACKGROUND
Brain natriuretic peptide is a novel natriuretic peptide that is secreted predominantly from the ventricles, and its plasma levels have been shown to be markedly increased in patients with chronic congestive heart failure. This study was designed to examine the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in patients with acute myocardial infarction.

METHODS AND RESULTS
We examined the plasma levels of brain natriuretic peptide as well as atrial natriuretic peptide in 50 consecutive patients (36 men and 14 women; mean age, 66 years) with acute myocardial infarction over the time course of 4 weeks. The plasma level of brain natriuretic peptide was significantly increased on admission in patients with acute myocardial infarction compared with controls (92 +/- 28 versus 5.2 +/- 0.5 pg/mL, P < .01) and reached the peak level of 319 +/- 58 pg/mL at 16.4 +/- 0.7 hours after admission. Thereafter, the level decreased and then again increased, forming the second peak of 277 +/- 66 pg/mL on day 5. The level then decreased gradually but was still much higher in the fourth week than that of controls (149 +/- 47 versus 5.2 +/- 0.5 pg/mL, P < .001). On the other hand, the plasma atrial natriuretic peptide level already had been increased at the time of admission compared with controls (116 +/- 14 versus 39.5 +/- 2.6 pg/mL, P < .01) and decreased thereafter, again increasing and making a small peak on day 2 to 3. The time course of the plasma brain natriuretic peptide level could be divided into two patterns: a monophasic pattern with one peak at about 16 hours after admission and a biphasic pattern with two peaks at about 16 hours and 5 days after admission. There were significantly more patients with anterior infarction, congestive heart failure, higher level of maximal creatine kinase-MB isoenzyme, and lower left ventricular ejection fraction in the biphasic group than in the monophasic group.

CONCLUSIONS
We conclude that the plasma level of brain natriuretic peptide is increased markedly in patients with acute myocardial infarction and may reflect the degree of left ventricular dysfunction in these patients.
Molecular forms of atrial natriuretic factor in normal and failing human myocardium.
Authors: Rodeheffer R J , Naruse M , Atkinson J B , Naruse K , Burnett J C , Merrill W H , Frist W H , Demura H , Inagami T 
Published: June 2012

BACKGROUND
Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart.

METHODS AND RESULTS
We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF.

CONCLUSIONS
These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.
LDL subclass phenotypes and the insulin resistance syndrome in women.
Authors: Selby J V , Austin M A , Newman B , Zhang D , Quesenberry C P , Mayer E J , Krauss R M 
Published: June 2012

BACKGROUND
Low-density lipoprotein (LDL) subclass phenotype B, characterized by predominance of small, dense LDL particles, is associated with elevated plasma triglycerides and apolipoprotein B and with lower high-density lipoprotein (HDL) cholesterol and apolipoprotein A-I. Because these abnormalities resemble the dyslipidemia of insulin resistance, we examined associations of LDL subclass phenotype with plasma insulin levels and with other aspects of the insulin resistance syndrome.

METHODS AND RESULTS
LDL subclass phenotypes were determined by gradient gel electrophoresis in 682 female twins aged 30 to 91 years who participated in the second examination of the Kaiser Permanente Women Twins Study. Prevalence of phenotype B and the intermediate phenotype (I) increased strongly with age, obesity, and non-insulin-dependent diabetes. In multivariate analysis of nondiabetic women, phenotype B or I was independently associated with each aspect of the insulin resistance syndrome, including higher plasma triglycerides, waist-hip ratio, fasting and postload insulin levels, and systolic blood pressure and lower HDL cholesterol levels after adjustment for age and body mass index. The prevalence of phenotype B or I rose progressively from 5.6% in women with no manifestations of the insulin resistance syndrome to 100% in women with four syndrome components. In 25 nondiabetic, monozygotic twin pairs discordant for subclass phenotype, the twins with phenotype B (or I) had significantly higher levels of body mass index, waist-hip ratio, and systolic blood pressure than their twins with phenotype A. Thus, nongenetic variation in these risk factors is important in explaining their associations with LDL subclass phenotype.

CONCLUSIONS
Small, dense LDL is an integral feature of the insulin resistance syndrome. Nongenetic (ie, behavioral or environmental) factors are important for the expression of the phenotype and for its association with other heart disease risk factors.
Suppression of insulin-induced sympathetic activation and vasodilation by dexamethasone in humans.
Authors: Scherrer U , Vollenweider P , Randin D , Jéquier E , Nicod P , Tappy L 
Published: June 2012

BACKGROUND
Physiological hyperinsulinemia in lean human subjects stimulates sympathetic nerve activity and blood flow in skeletal muscle, but the underlying mechanism is unknown. Potential mechanisms include central neural or peripheral actions of insulin. Glucocorticoids may potentially interfere with both such actions and thereby may attenuate sympathoexcitatory and vasodilatory effects of insulin in skeletal muscle.

METHODS AND RESULTS
To determine whether insulin-induced sympathetic activation and vasodilation are attenuated by dexamethasone, we measured muscle sympathetic nerve activity and muscle blood flow during euglycemic hyperinsulinemia before and after short-term administration of this pharmacological agent. Insulin concentrations, which normally doubled sympathetic activity and markedly increased blood flow, had no such stimulatory effect after short-term dexamethasone administration. In contrast, responses to two noninsulin sympathetic stimuli, the Valsalva maneuver and immersion of the hand in ice water, and the vasodilatory response to calf vascular occlusion were not altered by dexamethasone.

CONCLUSIONS
These results demonstrate a dramatic impairment of insulin-induced sympathetic activation and vasodilation by dexamethasone in lean, healthy humans. This study suggests that dexamethasone administration to lean subjects may offer an experimental model to examine underlying mechanisms that regulate the interplay between cardiovascular, sympathetic, and metabolic effects of insulin.