bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multivariate prediction of in-hospital mortality associated with coronary artery bypass graft surgery. Northern New England Cardiovascular Disease Study Group.
Authors: O'Connor G T , Plume S K , Olmstead E M , Coffin L H , Morton J R , Maloney C T , Nowicki E R , Levy D G , Tryzelaar J F , Hernandez F 
Published: June 2012

BACKGROUND
A prospective regional study was conducted to identify factors associated with in-hospital mortality among patients undergoing isolated coronary artery bypass graft surgery (CABG). A prediction rule was developed and validated based on the data collected.

METHODS AND RESULTS
Data from 3,055 patients were collected from five clinical centers between July 1, 1987, and April 15, 1989. Logistic regression analysis was used to predict the risk of in-hospital mortality. A prediction rule was developed on a training set of data and validated on an independent test set. The metric used to assess the performance of the prediction rule was the area under the relative operating characteristic (ROC) curve. Variables used to construct the regression model of in-hospital mortality included age, sex, body surface area, presence of comorbid disease, history of CABG, left ventricular end-diastolic pressure, ejection fraction score, and priority of surgery. The model significantly predicted the occurrence of in-hospital mortality. The area under the ROC curve obtained from the training set of data was 0.74 (perfect, 1.0). The prediction rule performed well when used on a test set of data (area, 0.76). The correlation between observed and expected numbers of deaths was 0.99.

CONCLUSIONS
The prediction rule described in this report was developed using regional data, uses only eight variables, has good performance characteristics, and is easily available to clinicians with access to a microcomputer or programmable calculator. This validated multivariate prediction rule would be useful both to calculate the risk of mortality for an individual patient and to contrast observed and expected mortality rates for an institution or a particular clinician.
Quantitative histological analysis of the human sinoatrial node during growth and aging.
Authors: Shiraishi I , Takamatsu T , Minamikawa T , Onouchi Z , Fujita S 
Published: June 2012

BACKGROUND
Fibrosis or fatty infiltration of the human sinoatrial (SA) node is generally believed to represent replacement of the SA nodal cells by connective tissue. Quantitative analysis, however, has not been performed precisely to validate the interpretation of such histological changes.

METHODS AND RESULTS
The actual volume of the SA node and its components were calculated according to the sum of the pixel number representing the colors of SA nodal cells and connective tissue in serial sections using a digital color image analyzer. Average volume occupied by the total SA nodal cells in adolescents and adults (n = 7) was 3.55 +/- 0.45 mm3, which was 2.4 times greater than that in infants (n = 3). The rate of increase was smaller than that of the total SA node (4.2 times, 16.68 +/- 2.56 mm3 in adolescents and adults). The considerable discrepancy in the growth ratio between the SA nodal cells and the total SA node resulted from an increase in the volume of connective tissue (7.4 times). In the elderly (n = 9), the volume of total SA node and SA nodal cells actually decreased (13.10 +/- 1.85 mm3 and 2.18 +/- 0.44 mm3), whereas that of fibrous connective tissue remained unchanged. Constant DNA ploidy patterns of SA nodal cells determined by cytofluorometry indicated that SA nodal cells never synthesize DNA during growth.

CONCLUSIONS
Until adulthood, the actual volume of SA nodal cells does not decrease, although the increase in volume ratio of the interstitial tissue to the total SA node has merely given a false impression of involution of SA nodal cells. Atrophy of SA nodal cells, however, occurs during aging together with reduction of the SA node and/or infiltration of fatty tissue.
Association between rheology and components of lipoproteins in human blood. Results from the MONICA project.
Authors: Koenig W , Sund M , Ernst E , Mraz W , Hombach V , Keil U 
Published: June 2012

BACKGROUND
Recent studies have suggested that several hemostatic factors, leukocyte count, and plasma viscosity are predictive of coronary heart disease. Detailed analyses on lifestyle correlates, in particular plasma lipids and lipoproteins, of determinants of blood rheology have not been reported from epidemiological studies.

METHODS AND RESULTS
We studied the relation between determinants of blood rheology and components of lipoproteins in a large sample of a population aged 25-64 years. The rheological parameters investigated were plasma viscosity, hemoglobin, and total serum protein; the lipoprotein variables included total cholesterol, high density lipoprotein (HDL) cholesterol, and the apoproteins A-I, A-II, and B. Covariables considered for possible confounding effects were age, body mass index, smoking behavior, alcohol consumption, and hypertension. Plasma viscosity was found to have a positive linear association with total cholesterol and apoprotein B (partial correlations after adjustment for all covariables including total serum protein for men and women were r = 0.23/0.19 and 0.24/0.25, respectively) and a small negative linear association with HDL cholesterol (r = -0.14/-0.10) and with apoprotein A-I (r = -0.08/-0.06). Polynomial regression showed a strong quadratic relation with HDL cholesterol in men, whereas no other variable revealed an appreciable deviation from linearity. The covariables had only a small, if any, confounding effect. Total serum protein, after control for the covariables, appeared to be associated only with total cholesterol. No association was found with hemoglobin.

CONCLUSIONS
We conclude that rheological mechanisms may be involved in the pathogenesis of ischemic syndromes in hyperlipidemias. However, the finding that in particular men with very low HDL cholesterol exhibit increased plasma viscosity cannot be explained in pure rheological terms but may be, at least in part, the result of concomitant hypertriglyceridemia. This was not assessed in this study.
Noninvasive measurement of the time constant of left ventricular relaxation using the continuous-wave Doppler velocity profile of mitral regurgitation.
Authors: Chen C , Rodriguez L , Levine R A , Weyman A E , Thomas J D 
Published: June 2012

BACKGROUND
The time constant of isovolumic relaxation (tau) is an important parameter of ventricular diastolic function, but the need for invasive measurement with high-fidelity catheters has limited its use in general clinical cardiology. The Doppler mitral regurgitant velocity spectrum can be used to estimate left ventricular (LV) pressure throughout systole and may provide a new noninvasive method for estimating tau.

METHODS AND RESULTS
Mitral regurgitation was produced in nine dogs, and ventricular relaxation was adjusted pharmacologically and with hypothermia. High-fidelity ventricular pressures were recorded, and tau was calculated from these hemodynamic data (tau H) assuming a zero-pressure asymptote. Continuous-wave mitral regurgitant velocity profiles were obtained, and the ventriculo-atrial (VA) pressure gradient was calculated by the simplified Bernoulli equation; tau was calculated from the Doppler data from the time of maximal negative dP/dt until LV-LA pressure crossover. Three methods were used to correct the Doppler VA gradient to better approximate the LV pressure before calculating tau: 1) adding actual LA V wave pressure (to yield tau LA); 2) adding 10 mm Hg (tau 10); and 3) no adjustment at all (actual VA gradient used to calculate tau 0). The agreement between tau H and the three Doppler estimates of tau was assessed by linear regression and by the mean and standard deviation of the error between the measurements (delta tau). the measurements (delta tau). tau H ranged from 29 to 135 msec. Without correction for LA pressure, the Doppler estimate of tau seriously underestimated tau H: tau 0 = 0.30 tau H + 9.4, r = 0.79, delta tau = -35 +/- 18 msec. This error was almost completely eliminated by adding actual LA pressure to the VA pressure gradient: tau LA = 0.92 tau H + 7.6, r = 0.95, delta tau = 2 +/- 7 msec. Addition of a fixed LA pressure estimate of 10 mm Hg to the VA gradient yielded an estimate that was almost as good: tau 10 = 0.89 tau H + 4.9, r = 0.88, delta tau = -2 +/- 12 msec. In general, tau was overestimated when actual LA pressure was below this assumed value, and vice versa. Numerical analysis demonstrated that assuming LA pressure to be 10 mm Hg should yield estimates of tau accurate to +/- 15% between true LA pressures of 5 and 20 mm Hg.

CONCLUSIONS
This study demonstrates that the Doppler mitral regurgitant velocity profile can be used to provide a direct and noninvasive measurement of tau. Because mitral regurgitation is very common in cardiac patients, this method may allow more routine assessment of tau in clinical and research settings, leading to a better understanding of the role of impaired ventricular relaxation in diastolic dysfunction and the effect of therapeutic interventions.
Protamine releases endothelium-derived relaxing factor from systemic arteries. A possible mechanism of hypotension during heparin neutralization.
Authors: Pearson P J , Evora P R , Ayrancioglu K , Schaff H V 
Published: June 2012

BACKGROUND
When used to reverse the anticoagulant effect of heparin, protamine sulfate often causes vasodilation that can lead to systemic hypotension. Protamine is rich in the basic amino acid arginine, which is the precursor of endothelial cell synthesis of nitric oxide, and nitric oxide is the active component of endothelium-derived relaxing factor (EDRF).

METHODS AND RESULTS
To determine whether the hypotensive effect of protamine could be due to stimulated release of EDRF, we studied rings (4-5 mm) of canine coronary, femoral, and renal artery suspended in organ chambers containing physiological salt solution (37 degrees C and 95% O2-5% CO2). Arterial rings with and without endothelium were contracted with prostaglandin F2 alpha (2 x 10(-6) M) and exposed to increasing concentrations of protamine (final organ bath concentration, 40-400 micrograms/ml). In arterial segments without endothelium, protamine caused only a modest decrease in tension. However, protamine induced concentration-dependent relaxation in all arterial segments with endothelium, which was significantly greater than in segments without endothelium (p less than 0.05). The endothelium-dependent relaxation induced by protamine was inhibited by NG-monomethyl-L-arginine (L-NMMA) (10(-5) M), but L-NMMA had no effect on rings without endothelium. The action of L-NMMA could be reversed by L-arginine (10(-4) M) but not D-arginine (10(-4) M).

CONCLUSIONS
This study demonstrates that protamine stimulates the release of EDRF from arterial endothelium, and that endothelium-dependent vasodilation may be an important cause of systemic hypotension during protamine infusion.
Evidence for transient linking of atrial excitation during atrial fibrillation in humans.
Authors: Gerstenfeld E P , Sahakian A V , Swiryn S 
Published: June 2012

BACKGROUND
Atrial fibrillation is usually thought of as a "random" pattern of circulating wavelets. However, local atrial activation should be influenced by the constant anatomy and receding tail of refractoriness from the previous activation. The general tendency for wave fronts to follow paths of previous excitation has been termed "linking." We examined intra-atrial electrograms recorded during atrial fibrillation for evidence of linking.

METHODS AND RESULTS
Two minutes of atrial fibrillation were recorded in 15 patients with an orthogonal catheter. We have previously demonstrated that this catheter can be used to detect changes in the direction of local atrial activation. A mean vector was calculated for each electrogram. The similarity of the direction of the vectors from two consecutive electrograms can be quantified on a scale of 1 to -1 by calculating the cosine (cos) of the smallest angle (theta) between them. Two vectors pointing in the same or opposite directions then have cos(theta) = 1 or -1, respectively. For the entire group of patients, mean cos(theta) was significantly greater than 0 (mean, 0.36; p less than 0.001). In nine of 15 patients, there were groups of six or more consecutive beats (total, 44 groups; range, six to 14 beats per group) in which the direction of activation of each beat was within 30 degrees of the previous beat. The likelihood of one group of six or 14 consecutive similar beats occurring by chance in any one patient in 1 minute is less than 0.05 and less than 0.0000001, respectively. There was a significant correlation (r = 0.90) between the amount of linking during the first and second minutes of atrial fibrillation in each patient.

CONCLUSIONS
Transient similarities in the direction of wavelet propagation in the majority of patients with atrial fibrillation is consistent with the presence of transient linking. To our knowledge, this is the first direct evidence that atrial activation during atrial fibrillation in humans is not entirely random.
Electrocardiographic body surface mapping in patients with ventricular tachycardia. Assessment of utility in the identification of effective pharmacological therapy.
Authors: Mitchell L B , Hubley-Kozey C L , Smith E R , Wyse D G , Duff H J , Gillis A M , Horacek B M 
Published: June 2012

BACKGROUND
Body surface maps of net QRST deflection areas (isointegrals) reflect regional ventricular repolarization properties. Vulnerability to ventricular tachyarrhythmias is associated with maps that feature multiple islands (extrema) of positive and negative values; such maps reflect regional disparity of ventricular recovery properties. The value of body surface mapping in prediction of the efficacy of antiarrhythmic therapy for ventricular tachyarrhythmias has not been determined.

METHODS AND RESULTS
Isointegral ECG body surface mapping was performed in 51 patients with inducible ventricular tachycardia having programmed stimulation studies at baseline and after oral quinidine therapy. The degree of nondipolarity of QRST isointegral distribution was expressed by the number of extrema and by the percentage contribution of nondipolar eigenvectors after Karhunen-Loeve transformation. QRST isointegral nondipolarity was greater in ventricular tachycardia patients than in 51 age- and sex-matched normal subjects expressed as mean number of extrema (4.1 +/- 2.8 versus 2.0 +/- 0.2, respectively), mean eigenvector-determined nondipolar content percentages (12.4 +/- 10.1% versus 4.5 +/- 4.9%), prevalence of abnormal numbers of extrema (63% versus 4%), or prevalence of abnormal nondipolar content percentages (33% versus 4%) (each p less than 0.01). Quinidine prevented ventricular tachycardia induction in 14 patients. Patients for whom quinidine was or was not effective had similar nondipolarity indexes at baseline. However, maps on quinidine differed as a function of antiarrhythmic efficacy. Although effective therapy produced no significant mean changes in nondipolarity, ineffective therapy increased the number of extrema compared with baseline (5.4 +/- 3.4 versus 3.8 +/- 2.5, respectively) (p = 0.002). Individually, 43% of patients on effective therapy had drug-induced decreases in numbers of extrema compared with 14% of those on ineffective therapy (p = 0.02). Furthermore, 29% of patients on effective therapy showed drug-induced increases in numbers of extrema compared with 62% of those on ineffective therapy (p = 0.03).

CONCLUSIONS
QRST isointegral body surface mapping shows promise as a noninvasive measure of drug efficacy in patients with ventricular tachycardia.
A recombinant, chimeric enzyme with a novel mechanism of action leading to greater potency and selectivity than tissue-type plasminogen activator.
Authors: Robinson J H , Browne M J , Carey J E , Chamberlain P D , Chapman C G , Cronk D W , Dodd I , Entwisle C , Esmail A F , Kalindjian S B 
Published: June 2012

BACKGROUND
Early intervention with thrombolytic agents has been shown unequivocally to reduce mortality after acute myocardial infarction. Presently used agents have disadvantages such as short half-life, immunogenicity, hypotension, and bleeding complications. Therefore, there is a need to develop improved thrombolytic drugs with novel mechanisms of action leading to improved properties.

METHODS AND RESULTS
Hybrid plasminogen/tissue-type plasminogen activator (t-PA) complementary DNA was constructed and expressed in Chinese hamster ovary cells. The chimeric protein, comprising the fibrin-binding domains of plasminogen covalently linked to the catalytic domain of t-PA, was purified and evaluated in vitro and in vivo. The hybrid was inhibited rapidly in human and animal plasmas. The mediator of this rapid inhibition was shown to be alpha 2-antiplasmin. The active center of the hybrid could be protected by reversible active center acylation with a novel inverse acylating agent, 4'-amidinophenyl-4-chloroanthranilic acid (AP-CLAN). An acylated (CLAN-) hybrid was cleared from the bloodstream of guinea pigs at 0.35 +/- 0.02 ml/min.kg-1 compared with a clearance rate of 36 +/- 4 ml/min.kg-1 for t-PA. The CLAN-plasminogen/t-PA hybrid was evaluated in a quantitative, "humanized" guinea pig pulmonary embolism model and shown to be approximately threefold more potent when given by bolus than an infusion of t-PA. Furthermore, the acylated hybrid was more fibrin selective than t-PA as determined by the relation between clot lysis and fibrinogen degradation.

CONCLUSIONS
An acylated, recombinant plasminogen/t-PA hybrid has sufficiently slow clearance to be administered by bolus and is more potent and fibrin selective than t-PA in vivo.
Severe right ventricular pressure loading in fetal sheep augments global myocardial blood flow to submaximal levels.
Authors: Reller M D , Morton M J , Giraud G D , Wu D E , Thornburg K L 
Published: June 2012

BACKGROUND
It has previously been shown that the fetal right ventricle (RV) is sensitive to changes in arterial pressure and that its stroke volume is significantly reduced with acute increases in pulmonary arterial pressure. However, the myocardial blood flow (MBF) response to increases in pulmonary arterial pressure have not been investigated in the fetus.

METHODS AND RESULTS
To assess whether the RV afterload sensitivity to arterial pressure is associated with limitation in MBF, seven fetal lambs were instrumented at 130 days of gestation with a pulmonary arterial occluder and intravascular catheters. RV stroke volume was measured by an electromagnetic flow probe and MBF by 15-microns labeled microspheres. MBF was determined at baseline and during incremental increases in pulmonary arterial pressure. Maximal MBF was determined in seven additional fetuses during adenosine infusion. The highest tolerated pressure was associated with a 50% reduction in RV stroke volume. The highest pulmonary arterial occlusion pressure resulted in a doubling of MBF to all regions of the heart (266 +/- 99 to 504 +/- 158, 193 +/- 69 to 387 +/- 100, and 171 +/- 66 to 338 +/- 134 ml/min/100 g for the RV, septum, and left ventricle, respectively). The best correlation for increases in both RV and global MBF was the RV heart rate-systolic pulmonary pressure product. Adenosine infusion was associated with a threefold increase in global MBF that was significantly greater than the MBF achieved during pulmonary arterial occlusion.

CONCLUSIONS
The fetal RV sensitivity to acute pressure loading is not associated with limitation of MBF. The fetal myocardium has a remarkable flow reserve that allows for preservation of function during acute increases in arterial pressure.
Abnormal laterality and congenital cardiac anomalies. Relations of visceral and cardiac morphologies in the iv/iv mouse.
Authors: Seo J W , Brown N A , Ho S Y , Anderson R H 
Published: June 2012

BACKGROUND
In the management of hearts with deranged laterality, it is essential that the left and right atrial chambers are correctly identified. There are two major approaches, which are based on venous connections or on the morphology of the atrial appendages, and there is no consensus as to which is the most useful. We used the iv/iv mouse mutant, which is known to be pertinent to this problem, to evaluate the relations of cardiac defects with atrial, venous, and other visceral morphologies.

METHODS AND RESULTS
The morphology of the heart and other organs was examined in 275 iv/iv mice using criteria based on abnormal laterality in humans. The arrangement of the atrial appendages was determined by morphological examination of the junction between the appendage and the venous component of the atrium. On this basis, 45.1% of cases were shown to have usual atrial arrangement, 50.2% had mirror imagery, 1.5% had right isomerism, and 3.3% had left isomerism. Every case of atrial isomerism had a cardiac lesion; the morphological types were similar to those seen in human cases. Of cases with either usual or mirror-image arrangement of the appendages, 33.2% had abnormal spleens, but only 3.1% had cardiac defects. Similarly, venous abnormalities were much more common (30.1%) than cardiac defects.

CONCLUSIONS
Study results endorse the importance of the morphology of atrial appendages in predicting cardiac abnormalities and point to the marked inconsistency of the arrangement of other organs, including the spleen and the connections of the systemic veins.