bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic implications of baseline electrocardiographic features and their serial changes in subjects with left ventricular hypertrophy.
Authors: Levy D , Salomon M , D'Agostino R B , Belanger A J , Kannel W B 
Published: June 2012

BACKGROUND
During the past half-century, the ECG has been used extensively for the diagnosis of left ventricular hypertrophy. Persons with ECG evidence of left ventricular hypertrophy are at increased risk for the development of cardiovascular disease.

METHODS AND RESULTS
Subjects from the Framingham Heart Study with ECG evidence of left ventricular hypertrophy were eligible for this investigation if they were free of cardiovascular disease and did not have complete bundle-branch block or Wolff-Parkinson-White syndrome. Logistic regression analyses of pooled biennial examinations were used to determine risk for cardiovascular disease as a function of baseline voltage (sum of R wave in aVL plus S wave in V3) and repolarization and as a function of serial changes in these ECG features of hypertrophy. The eligible sample consisted of 274 men (mean age, 60 years) and 250 women (mean age, 64 years) who contributed 2660 person-examinations. During follow-up, there were 269 new cardiovascular events. Compared with subjects in the first quartile of voltage at baseline, the age-adjusted odds ratio for cardiovascular disease among subjects in the fourth quartile was 3.08 (95% confidence interval [CI], 1.87 to 5.07) in men and 3.29 (95% CI, 1.78 to 6.09) in women. Compared with a normal repolarization pattern, the presence of severe repolarization abnormalities was associated with an age-adjusted odds ratio of 5.84 (95% CI, 3.55 to 9.62) in men and 2.47 (95% CI, 1.38 to 4.42) in women. Subjects with a serial decline in voltage were at lower risk for cardiovascular disease than were those with no serial change (men: odds ratio after adjusting for age and baseline voltage, 0.46; 95% CI, 0.26 to 0.84; women: odds ratio, 0.56; 95% CI, 0.30 to 1.04). In contrast, those with a serial increase in voltage were at greater risk for cardiovascular disease (men: odds ratio, 1.86; 95% CI, 1.14 to 3.03; women: odds ratio, 1.61; 95% CI, 0.91 to 2.84). Compared with those with no serial change, an improvement in repolarization was associated with a marginally significant reduction in cardiovascular risk in men (odds ratio after adjusting for age and baseline repolarization, 0.45; 95% CI, 0.20 to 1.01). Worsening of repolarization was associated with increased risk for cardiovascular disease in both sexes (men: odds ratio, 1.89; 95% CI, 1.05 to 3.40; women: odds ratio, 2.02; 95% CI, 1.07 to 3.81).

CONCLUSIONS
The results of this investigation suggest that regression of ECG features of left ventricular hypertrophy confers an improvement in risk for cardiovascular disease, whereas serial worsening imposes increased risk. The benefits to be derived from regression of left ventricular hypertrophy must be confirmed in other clinical settings.
Arterial baroreflex control of renal hemodynamics in humans.
Authors: van Tilborg K A , Rabelink T J , van Rijn H J , Boomsma F , Koomans H A 
Published: June 2012

BACKGROUND
Control of renal hemodynamics by the arterial baroreflex has never been proved in humans. Apart from the physiological viewpoint, this issue is relevant because altered baroreflex function has been implicated in the pathogenesis of human hypertension.

METHODS AND RESULTS
Renal function studies were performed in seated healthy volunteers (n = 12; age range, 20 to 34 years) during sustained neck suction at -60 mm Hg, aiming to selectively activate the carotid sinus arterial baroreceptors. Two protocols were followed. One group of 6 volunteers taking a 20 mmol/d sodium diet underwent 90 minutes of neck suction. Compared with a time-control study, neck suction decreased arterial pressure and heart rate; increased glomerular filtration rate (inulin clearance) from 104 +/- 6 to 114 +/- 8 mL/min (P < .01), renal plasma flow (para-aminohippurate clearance) from 616 +/- 52 to 665 +/- 42 mL/min (P < .01), and renal blood flow (from 1120 +/- 95 to 1209 +/- 77 mL/min, P < .01); and decreased renal vascular resistance (from 86 +/- 8 to 76 +/- 6 mm Hg.min.L-1, P < .01). Neck suction had no effect on plasma renin activity, aldosterone, atrial natriuretic peptide, catecholamines, and renal sodium excretion. The other 6 volunteers took a normal sodium diet and underwent sustained neck suction for 60 minutes. In this group, no effects on renal hemodynamics could be discerned, despite a modest decrease in blood pressure and heart rate.

CONCLUSIONS
These data show, for the first time, that the arterial baroreflex is involved in the control of renal hemodynamics in humans. However, basal arterial baroreflex control of renal hemodynamics is probably low, and arterial baroreflex activation with subsequent renal vasorelaxation may be found only in conditions in which basal arterial baroreflex control of kidney function is significant, as is presumably the case in seated sodium-restricted subjects.
Fibrin-targeted recombinant hirudin inhibits fibrin deposition on experimental clots more efficiently than recombinant hirudin.
Authors: Bode C , Hudelmayer M , Mehwald P , Bauer S , Freitag M , von Hodenberg E , Newell J B , Kübler W , Haber E , Runge M S 
Published: June 2012

BACKGROUND
Although the indirect thrombin inhibitor heparin and the more potent direct inhibitor hirudin are useful in preventing thrombosis, a substantial opportunity remains for improving the thrombus selectivity of thrombin inhibitors.

METHODS AND RESULTS
To explore the effect of targeting an antithrombin to the surface of a clot, we covalently linked recombinant hirudin to the Fab' (or IgG) of a monoclonal antibody (59D8) that selectively binds to an epitope on fibrin that becomes exposed only after thrombin cleaves fibrinopeptide B. Antibody-coupled hirudin bound to an immobilized peptide of the fibrin beta-chain amino-terminal sequence and inhibited the peptidolytic activity of thrombin more efficiently than free hirudin. Thrombin inhibition dependent on binding to immobilized fibrin monomer was enhanced 1100-fold (P < .0001). Hirudin-59D8 Fab' was 10 times more effective than hirudin in inhibiting fibrin deposition on experimental clot surfaces in fibrinogen solution (P < .0001) and human plasma (P < .0001). The more effective inhibition of thrombin by the conjugate was supported by significantly diminished concentrations of fibrinopeptide A in the plasma supernatant of the clot (P = .0001). Inhibition of clotting by an uncoupled mixture of hirudin and 59D8 Fab' was indistinguishable from that by hirudin alone, indicating that the conjugate's greater inhibitory activity was due to the covalent linkage between antibody and hirudin.

CONCLUSIONS
Fibrin-targeted hirudin (in comparison with unmodified hirudin) significantly reduces fibrin deposition on the surface of experimental clots.
Nitric oxide accounts for dose-dependent estrogen-mediated coronary relaxation after acute estrogen withdrawal.
Authors: Collins P , Shay J , Jiang C , Moss J 
Published: June 2012

BACKGROUND
Estrogen replacement therapy reduces the risk of coronary heart disease in postmenopausal women, and estrogen treatment modulates endothelium-dependent vasodilation in ovariectomized, atherosclerotic monkeys. Estradiol-17 beta also induces relaxation in isolated rabbit coronary arteries as well as cerebral basilar arteries. The estrogen concentrations required to induce such relaxation are in the pharmacological range (10(-6) to 10(-5) mol/L).

METHODS AND RESULTS
The present study was designed to test whether the sensitivity and specificity of the relaxing response of coronary vascular smooth muscle to exogenous estradiol-17 beta is dependent on the sex hormone status of the animal. In coronary artery rings contracted with PGF2 alpha (3 x 10(-5) mol/L), estradiol-17 beta caused significant relaxation at a physiological estrogen concentration (10(-9) mol/L), in coronary artery rings from oophorectomized, estrogen-treated and acutely estrogen-withdrawn rabbits only. Relaxation induced by estradiol-17 beta at lower concentrations (10(-9) to 10(-6) mol/L) in these rings was 20 +/- 6%, 42 +/- 8%, 54 +/- 9%, and 75 +/- 8%, respectively, compared with 4 +/- 2%, 12 +/- 5%, 16 +/- 7%, and 25 +/- 12% and 5 +/- 2%, 12 +/- 5%, 18 +/- 8%, and 23 +/- 10% in rings from estrogen-maintained and oophorectomized rabbits, respectively (P < .01). The relaxation in coronary artery rings from estrogen-treated and acutely estrogen-withdrawn rabbits was endothelium and nitric oxide dependent since it was abolished by endothelium removal and the nitric oxide synthase inhibitor N omega-nitro-L-arginine.

CONCLUSIONS
This study demonstrates that estrogen-induced, endothelium-dependent relaxation of coronary arteries may, in some species, depend on the sex hormone status of the animal. These findings may help to better understand the effects of ovarian steroids in the coronary circulation of females.
A polymorphism of the angiotensinogen gene associated with variation in blood pressure in a genetic isolate.
Authors: Hegele R A , Brunt J H , Connelly P W 
Published: June 2012

BACKGROUND
The Hutterite Brethren are a genetic isolate characterized by high indices of relatedness and a communal agrarian lifestyle. We hypothesized that variation of the angiotensinogen (AGT) and angiotensin-converting enzyme (ACE) genes would be associated with variation in resting blood pressure in this group. We also hypothesized that the association would depend on the sex of the subjects.

METHODS AND RESULTS
In 741 Hutterites, we measured blood pressure in quadruplicate and analyzed DNA for genotypes of an insertion/deletion (I/D) polymorphism of ACE and of two protein polymorphisms of AGT, namely, M235T and T174M. We tested for association between variation in systolic and diastolic blood pressures and genotypic class. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure. We also tested for an interaction between the AGT genotype and sex. We observed that genotypes of AGT codon 174 were significantly associated with variation in systolic blood pressure only in men. The AGT codon 174 polymorphism accounted for 3.1% of the total variation in systolic blood pressure in men.

CONCLUSIONS
The association of AGT variation with resting blood pressure in men is consistent with the existence of important structural elements within, flanking, or proximal to the AGT gene, whose functional impact might be related to differences in sex.
Short stature and risk for mortality and cardiovascular disease events. The Framingham Heart Study.
Authors: Kannam J P , Levy D , Larson M , Wilson P W 
Published: June 2012

BACKGROUND
Several studies have observed an inverse association between height and risk for coronary disease, but it is unclear whether other traditional coronary disease risk factors may have confounded this association. We examined the original Framingham Heart Study cohort to determine whether short stature is associated with all-cause mortality, cardiovascular disease mortality, and myocardial infarction after adjusting for age and other traditional coronary heart disease risk factors.

METHODS AND RESULTS
A total of 2019 men and 2585 women were followed up to 35.6 years. Subjects were stratified by sex and divided into quartiles according to height. Risk ratios were calculated from proportional hazards analyses comparing the first, second, and third quartiles of height to the tallest quartile before and after adjusting for age, hypertension, smoking, serum cholesterol, diabetes, relative weight, and alcohol intake. In both sexes, there were significant differences in the unadjusted event rates between the shortest and the tallest quartile for all-cause mortality, cardiovascular mortality, and myocardial infarction. Once the analyses were age adjusted, differences among height quartiles persisted only for risk of myocardial infarction in women. Further adjustment for other clinical variables had little additional impact on the results.

CONCLUSIONS
After considering age and other coronary disease risk factors, short stature was not associated with increased risk for all-cause or cardiovascular mortality in either sex. It was associated with increased risk for myocardial infarction in women but not in men.
Role of protein kinase C-mediated pathway in the pathogenesis of coronary artery spasm in a swine model.
Authors: Ito A , Shimokawa H , Nakaike R , Fukai T , Sakata M , Takayanagi T , Egashira K , Takeshita A 
Published: June 2012

BACKGROUND
The intracellular mechanism of coronary artery spasm is still unknown. The pathway mediated by protein kinase C (PKC) is an important intracellular process of various cellular responses, including vascular smooth muscle contraction. Thus, we examined the role of the PKC-mediated pathway in the pathogenesis of coronary artery spasm in our in vivo swine model.

METHODS AND RESULTS
Seven Göttingen miniature pigs underwent coronary balloon injury and x-ray irradiation to induce atherosclerotic lesion. After 6 to 18 months, intracoronary serotonin (3 micrograms/kg) or histamine (3 micrograms/kg) repeatedly induced coronary artery spasm at the atherosclerotic site. At the spastic site, intracoronary administration of phorbol-12,13-dibutyrate (PDBu) (10(-9) mol/kg), a PKC-activating phorbol ester, also induced coronary artery spasm, which was completely blocked by pretreatment with intracoronary staurosporine (10 micrograms/kg), a PKC inhibitor. Intracoronary administration of an inactive phorbol ester, phorbol-12,13-didecanoate (10(-9) mol/kg), did not induce coronary vasoconstriction. Coronary artery spasm induced by the autacoids was significantly augmented by pretreatment with intracoronary PDBu and partially inhibited by staurosporine. Intracoronary administration of Bay K 8644 (10 micrograms/kg), a dihydropyridine-sensitive L-type calcium channel agonist, also induced coronary artery spasm at the spastic site, which was significantly inhibited by pretreatment with intracoronary staurosporine or nifedipine (0.1 mg/kg).

CONCLUSIONS
These results suggest (1) the PKC-mediated pathway is importantly involved in the pathogenesis of coronary artery spasm, (2) activation of the PKC-mediated pathway partially accounts for serotonin- and histamine-induced coronary artery spasm, and (3) at the spastic site, calcium influx through dihydropyridine-sensitive L-type calcium channel and/or calcium sensitivity of the contractile proteins may be augmented by the PKC-mediated pathway.
Right atrial and right ventricular transmural pressures in dogs and humans. Effects of the pericardium.
Authors: Hamilton D R , Dani R S , Semlacher R A , Smith E R , Kieser T M , Tyberg J V 
Published: June 2012

BACKGROUND
To determine the transmural pressure-dimension relations of the right atrium (RA) and right ventricle (RV) before and after pericardiectomy, six open-chest dogs were instrumented with pericardial balloons placed over the RA and RV free walls.

METHODS AND RESULTS
PA appendage dimensions and RV free-wall segment lengths were measured using sonomicrometry. Intact-pericardium RA and RV transmural pressures were calculated by subtracting the pericardial pressures (measured using balloons) from the cavitary pressures. Pooled data from six animals with pericardium intact indicate that at RA and RV cavitary pressures of 5, 10, and 15 mm Hg, RV pericardial pressure was 4.3 +/- 0.3, 8.6 +/- 1.0, and 13.3 +/- 1.5 mm Hg, respectively, and RA pericardial pressure was 4.8 +/- 0.3, 9.6 +/- 0.6, and 14.6 +/- 0.6 mm Hg, respectively (mean +/- SD). With calculated unstressed dimensions, the cavity dimension data were normalized to strain (in percent). We determined that in the dog, RV strain would increase by 14% and RA by 68% to maintain cavitary pressure at 10 mm Hg on pericardiectomy. To compare these results with clinical data, RV (n = 7) and RA (n = 6) transmural pressures were measured using balloons in patients (age, 19 to 76 years) undergoing cardiac surgery. RA transmural pressure of six patients was 1.0 +/- 1.5 mm Hg when central venous pressures (CVPs) ranged from 3 to 16 mm Hg. RV transmural pressure equaled 1.2 +/- 1.9, 2.3 +/- 1.9, and 3.4 +/- 2.0 mm Hg when CVP was 5, 10, and 15 mm Hg, respectively.

CONCLUSIONS
Pericardial constraint (as evaluated by the ratio of pericardial to intracavitary pressures when CVP is 10 mm Hg) accounted for 96% of RA cavitary pressure in the dog and 89% in humans and at least 86% of RV cavitary pressure in the dog and 77% in humans.
Radiofrequency ablation of slow pathway in patients with atrioventricular nodal reentrant tachycardia. Do arrhythmia recurrences correlate with persistent slow pathway conduction or site of successful ablation?
Authors: Manolis A S , Wang P J , Estes N A 
Published: June 2012

BACKGROUND
Residual slow pathway conduction in the form of persistent jump in the atrioventricular (AV) conduction time or atrial echo beats is a common finding after successful radiofrequency (RF) ablation of the slow pathway in patients with AV nodal reentrant tachycardia (AVNRT). Sites of successful RF ablation of the slow pathway may be located anteriorly in the tricuspid annulus (cephalad to the coronary sinus os) or posteriorly (at, within, or caudal to the coronary sinus os). The aim of this study was to investigate whether arrhythmia recurrences correlate with persistent slow pathway conduction or site of successful ablation.

METHODS AND RESULTS
Among 55 patients with symptomatic AVNRT having RF ablation, 23 patients (42%) (group 1) had evidence of persistent dual AV nodal pathway physiology and/or echo beats, whereas in 32 patients (group 2), slow pathway conduction had been completely eliminated. With regard to ablation sites, 14 patients (25%) (group A) had their slow pathway successfully ablated at an inferoposterior site, whereas in 41 patients (group B), the ablation site was located anteriorly to the coronary sinus os. The study patients included 17 men and 38 women, aged 37 +/- 18 years. The electrophysiological study and RF ablation were performed in a single session in 50 patients (91%). After the first session, the technique was successful in all patients (100%), with elimination of AVNRT and without affecting AV conduction. A mean of 9 +/- 6 lesions were applied. The total procedure time averaged 4 +/- 1 hours. Fluoroscopy time was 41 +/- 25 minutes. Except for transient AV block in 1 patient, no other complications occurred. Over 12 +/- 8 months, a total of 7 patients (13%) had recurrence of AVNRT, and 6 of them underwent successful repeat slow pathway RF ablation. Recurrence rate was 9% (2 patients) for group 1, with persistent jump or echo beats, and 16% (5 patients) for group 2, without residual slow pathway conduction (P = NS). Five of the recurrences (71%) were noted in group A and 2 in group B. Thus, the recurrence rate was 36% for group A (5 of 14 patients), with posterior ablations, and 5% for group B (2 of 41 patients), with anterior sites of successful RF ablation (P < .05).

CONCLUSIONS
After successful RF ablation of the slow pathway in patients with AVNRT, residual slow pathway conduction does not correlate with clinical tachycardia recurrences. However, the site of successful RF ablation of the slow pathway does correlate with arrhythmia recurrences. More recurrences are observed when the site is located inferoposteriorly, at or below the os of the coronary sinus, as compared with medial and anterior locations of the ablation site.
Oscillation of Blood Flow and Vascular Resistance During Mayer Waves
Authors: Killip Thomas 
Published: June 2012

In cats anesthetized with chloralose, Mayer waves developed following graded hemorrhage and, in some, partial carotid occlusion. The average Mayer wave was 56 mm. Hg in amplitude rising from a base systemic pressure of 70 mm. Hg at a frequency of 3.0 per minute. Rhythmic fluctuation of respiratory depth and frequency paralleled but slightly preceded the blood pressure change. There was no significant variation in heart rate during Mayer waves.
Flow in the abdominal aorta and vena cava varied inversely with systemic pressure. A flow lag of four to six seconds in the vena cava behind that in the aorta during Mayer waves was probably related to circulation time.
Blood flow was measured in muscle, small intestine, skin, and kidney. During the pressure rise of each Mayer wave, blood flow decreased in muscle more than in gut. Cutaneous flow increased moderately. Renal flow varied directly with the arterial pressure. Changes vascular resistance were evaluated by holding perfusion pressure constant and measuring regional blood flow. During Mayer waves, muscle vascular resistance increased 276 per cent, intestinal resistance increased 210 per cent, and cutaneous resistance rose 136 per cent. Renal vascular resistance did not change.
Since Mayer waves are apparently reflexogenic in origin, the data are interpreted as evidence for regional differences in the pattern of central reflex control of the peripheral vascular system.
Local Regulation of Effective Blood Flow in Muscle
Authors: HYMAN CHESTER , PALDINO R. L. , ZIMMERMANN EMERY 
Published: June 2012

The techniques of macro- and micro-tissue clearance were used to study reactive hyperemia. Clearance of radioactive iodide from gross injection sites in muscles of rabbits and clearance of micro-injected diffusible dye from the exposed, directly observed spinotrapezius of rats gave evidence for an exact quantitative repayment of effective blood flow debt. In both types of preparation a subnormal clearance followed a thermally induced hyperemia as an apparent compensation. The exact quantitative repayment and compensation support the hypothesis that local effective blood flow is in a steady-state relation to the local concentration in tissue fluid of some agent with vasodilating properties.
It is suggested that an extension of this method to studies of vasodilatation induced by drugs or other chemicals might offer an approach to identification of the normal vasodilator, and to physiological proof of its exact nature.