bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adjunctive intracoronary infusion of antithrombin III during percutaneous transluminal coronary angioplasty. Results of a prospective, randomized trial.
Authors: Schächinger V , Allert M , Kasper W , Just H , Vach W , Zeiher A M 
Published: June 2012

BACKGROUND
Heparin needs the plasma protein antithrombin III to function as an inhibitor of thrombin, and local antithrombin III deficiency might therefore limit the antithrombotic effectiveness of heparin during percutaneous transluminal coronary angioplasty.

METHODS AND RESULTS
In the present double-blind study, 615 consecutive patients undergoing percutaneous transluminal coronary angioplasty (PTCA), of a total of 713 stenoses, were prospectively randomized to receive a bolus injection of 15,000 U heparin followed by a continuous intracoronary infusion via the guiding catheter of either 250 U heparin per minute or 250 U heparin plus 25 U antithrombin III per minute during the procedure. Four clinical variables, 19 lesion-specific characteristics, and 16 procedure-related variables were evaluated. Procedural success was assessed by quantitative angiography; procedure-related ischemic complications were analyzed during in-hospital follow-up. Procedural success rates (< 50% final diameter stenosis and no major ischemic complication) were similar, with 85% in the heparin group (n = 324 patients) and 83% in the heparin+antithrombin III group (n = 291 patients). Percent diameter stenosis after PTCA was 39 +/- 18% in the heparin group and 40 +/- 20% in the heparin+antithrombin III group (NS). There were no differences between the two groups with respect to PTCA-related acute vessel occlusion, angiographic evidence of intracoronary thrombus formation, post-procedure creatine kinase increase, Q-wave myocardial infarction, or emergency coronary artery bypass surgery. High-risk subgroup analysis revealed no beneficial effect of adjunctive intracoronary antithrombin III in any of the analyzed subgroups. In addition, although risk stratification according to the criteria of the American College of Cardiology/American Heart Association Task Force classification proved to be very useful for the entire study population, no beneficial effect of intracoronary antithrombin III infusion was observed in any of the different risk groups.

CONCLUSIONS
Compared with heparin alone, adjunctive intracoronary antithrombin III therapy does not appear to have any beneficial effect on procedural outcome as well as type and frequency of acute complications during PTCA even in subgroups of patients with a high risk for thrombotic complications. Thus, a local deficiency of antithrombin III does not play a major role for the failure of heparin to abolish thrombotic complications during PTCA.
Role of nitric oxide in reactive hyperemia in human forearm vessels.
Authors: Tagawa T , Imaizumi T , Endo T , Shiramoto M , Harasawa Y , Takeshita A 
Published: June 2012

BACKGROUND
The role of nitric oxide (NO) in reactive hyperemia (RH) is not well known. We investigated whether NO plays a role in RH in human forearm vessels by examining the effects of NG-monomethyl-L-arginine (L-NMMA), a blocker of NO synthesis, on reactive hyperemic flow.

METHODS AND RESULTS
Forearm blood flow (FBF) was measured by strain-gauge plethysmography with a venous occlusion technique. The left brachial artery was cannulated for drug infusion and direct measurement of arterial pressure. To produce RH, blood flow to the forearm was prevented by inflation of a cuff on the upper arm to suprasystolic pressure for intervals of 3 and 10 minutes. After the release of arterial occlusion (AO), FBF was measured every 15 seconds for 3 minutes. Resting FBF was 4.3 +/- 0.3 mL.min-1.100 mL-1 before 3 minutes of AO and 4.1 +/- 0.6 mL.min-1.100 mL-1 before 10 minutes of AO. FBF increased to 32.3 +/- 1.9 and 38.2 +/- 3.1 mL.min-1.100 mL-1 immediately after 3 and 10 minutes of AO, respectively, and gradually decayed (n = 13). Intra-arterial infusion of L-NMMA (4 mumol/min for 5 minutes) decreased baseline FBF (P < .01) without changes in arterial pressure. L-NMMA did not affect the peak reactive hyperemic FBF after 3 and 10 minutes of AO. L-NMMA significantly decreased total reactive hyperemic flow (flow debt repayment) by 20% to 30% after 3 and 10 minutes of AO. Simultaneous infusion of L-arginine (a precursor of NO) with L-NMMA reversed the effects of L-NMMA.

CONCLUSIONS
Our results suggest that NO plays a minimal role in vasodilation at peak RH but plays a modest yet significant role in maintaining vasodilation after peak vasodilation. Our results also suggest that reactive hyperemia in human forearms is caused largely by mechanisms other than NO.
17 beta-Estradiol inhibits flow- and acute hypoxia-induced prostacyclin release from perfused endocardial endothelial cells.
Authors: Redmond E M , Cherian M N , Wetzel R C 
Published: June 2012

BACKGROUND
Because of the marked difference in the incidence and severity of cardiovascular diseases between men and premenopausal women, several groups have studied the effect of sex steroids, particularly estrogen, on vascular endothelial prostacyclin (PGI2) release. No previous studies have addressed the effect of estrogen on endocardial endothelial cells (EECs), which are involved in the modulation of the myocardium and potentially in downstream pulmonary and systemic vascular tone. Furthermore, all previous studies of estrogen effects on cultured endothelial cell function have used cells grown under standard static cell culture conditions, thereby ignoring the contribution of flow, the ubiquitous environmental endothelial stimulus.

METHODS AND RESULTS
The effect of 17 beta-estradiol pretreatment (100 ng/mL, 72 hours) on cultured sheep EEC PGI2 release in response to multiple physiologically relevant stimuli was studied. EECs were grown in six-well plates (static conditions) or on microcarrier beads and perfused at a constant flow with normoxic (PO2 = 150 mm Hg, PCO2 = 35 mm Hg) or hypoxic (PO2 = 35 mm Hg, PCO2 = 35 mm Hg) Krebs solution. The stable metabolite of PGI2, 6-keto-PGF1 alpha, was determined in samples from both static and perfusion experiments by direct radioimmunoassay. 17 beta-Estradiol pretreatment did not alter basal or stimulated (arachidonic acid, 1 mumol/L, 10 mumol/L; A23187, 10 mumol/L; and bradykinin, 1 mumol/L) PGI2 release in static conditions. Untreated and acutely treated (100 ng/mL added to perfusate) EECs responded to flow with a time-dependent increase in PGI2 release that plateaued between 60 and 100 minutes. In contrast, 17 beta-estradiol-pretreated, perfused EECs did not increase PGI2 release over time. During perfusion, acute hypoxia increased PGI2 release: 140 +/- 65 (normoxia) to 296 +/- 113 pg (hypoxia) 6-keto-PGF1 alpha/mg per minute. 17 beta-Estradiol inhibited hypoxia-induced PGI2 release: 296 +/- 113 pg (untreated EECs, hypoxia) versus 159 +/- 60 pg (17 beta-estradiol pretreated, hypoxia) 6-keto-PGF1 alpha/mg per minute.

CONCLUSIONS
This study demonstrates for the first time an inhibitory effect of 17 beta-estradiol on flow- and acute hypoxia-induced increase in PGI2 release from perfused EECs in the absence of any effect on pharmacologically stimulated PGI2 release from static cultures. These effects of 17 beta-estradiol may explain in part the well-recognized gender and estrogen effects in cardiovascular diseases and highlight the importance of flow in studies of endothelial cell function.
Correlation between decreased myocardial glucose phosphorylation and the DNA mutation size in myotonic dystrophy.
Authors: Annane D , Duboc D , Mazoyer B , Merlet P , Fiorelli M , Eymard B , Radvanyi H , Junien C , Fardeau M , Gajdos P 
Published: June 2012

BACKGROUND
Myotonic dystrophy, the most common form of adult dystrophy, has been shown to be caused by amplification of CTG triplet repeat in the 3' untranslated region of a protein kinase gene located on chromosome 19. Impaired glucose metabolism has been suggested as a possible explanation of brain and skeletal muscle involvement in this multisystem disease. We investigated whether myocardial glucose metabolism is impaired in myotonic dystrophy and whether this impairment is related to the size of the mutation.

METHODS AND RESULTS
The myocardial metabolic rate for glucose (MMRGlu, mumol.min-1.g-1), K1 (blood-to-tissue transfer constant), k2 (tissue-to-blood transfer constant), and k3 (phosphorylation rate constant) were determined in 7 control subjects and 12 patients with myotonic dystrophy by using parametric images generated from dynamic cardiac positron emission tomography (PET) and 18F-fluoro-2-deoxy-glucose studies. The expansion of the CTG triplet repeats was analyzed in patients with the probe cDNA25 after EcoRI digestion. Nonparametric tests were used to compare quantitative variables between control subjects and patients. The correlations between the size of the mutation and PET parameters were studied by linear regression. MMRGlu and k3 were significantly decreased in patients compared with control subjects (0.39 +/- 0.20 versus 0.64 +/- 0.25, P = .03, and 0.09 +/- 0.07 versus 0.24 +/- 0.21, P = .03, respectively), whereas K1 and k2 were not statistically different between control subjects and patients. MMRGlu and k3 correlate inversely with the length of the CTG triplet repeat (r = -.65 and P = .03 for MMRGlu, and r = -.85 and P = .001 for k3, respectively).

CONCLUSIONS
In myotonic dystrophy, the observed reductions in MMRGlu and phosphorylation are inversely linked to the length of the mutation. This observation suggests that impaired modulation of a protein kinase involved in myocardial hexokinase activation may give a pathophysiological schema to relate the molecular defect and the abnormal myocardial metabolism in myotonic dystrophy.
Evidence of genetic heterogeneity in Romano-Ward long QT syndrome. Analysis of 23 families.
Authors: Towbin J A , Li H , Taggart R T , Lehmann M H , Schwartz P J , Satler C A , Ayyagari R , Robinson J L , Moss A , Hejtmancik J F 
Published: June 2012

BACKGROUND
The Romano-Ward long-QT Syndrome (LQTS) is an autosomal dominant inherited trait characterized by prolonged QT interval on ECG, life-threatening arrhythmias, syncope, and sudden death in affected individuals. A gene responsible for this disorder has been shown to be linked to the Harvey ras-1 locus (H-ras-1) DNA marker on the short arm of chromosome 11 (11p) in 7 families. The purpose of this study was to determine, by analyzing 23 families with LQTS for linkage to chromosome 11p, whether evidence exists for more than one gene causing LQTS (ie, locus heterogeneity).

METHODS AND RESULTS
Twenty-three families (262 family members) were clinically evaluated using medical histories, ECGs, and Holter recordings. Each corrected QT interval (QTc) were determined using Bazett's formula. Blood for DNA extraction and cell line immortalization was obtained after informed consent. Southern blotting and polymerase chain reaction were performed, and linkage analysis carried out using the LINKAGE computer program (v 5.03). Genetic heterogeneity was determined using the HOMOG 2 (v 2.51) computer program. Twenty-three families were studied for evidence of linkage to chromosome 11p using the H-ras-1 locus probe pTBB-2 and multiple flanking markers, including tyrosine hydroxylase (TH). Two-point linkage analysis using pTBB-2 and TH markers was consistent with linkage in 15 of 23 families, with the maximum single-family LOD score of +3.038 occurring at theta = 0. However, 8 of 23 families had negative LOD scores, with the values in 4 families being less than -2 at theta = 0, consistent with exclusion of linkage. Analysis with the HOMOG program was consistent with genetic heterogeneity (P < .0001). Multipoint linkage data using pTBB-2 and TH were also examined for evidence of heterogeneity. HOMOG analysis of multipoint LOD scores from 100 cM surrounding the H-ras-1 locus also supported heterogeneity (P < .001).

CONCLUSIONS
In the 23 families with LQTS analyzed for linkage to the H-ras-1 locus on chromosome 11p15.5, 15 of 23 families had LOD scores consistent with linkage. The remaining 8 of 23 families had negative LOD scores, 4 of which were definitively excluded from linkage. Thus, genetic heterogeneity is definitively (P < .001) demonstrated for this disorder.
Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry.
Authors: Emond M , Mock M B , Davis K B , Fisher L D , Holmes D R , Chaitman B R , Kaiser G C , Alderman E , Killip T 
Published: June 2012

BACKGROUND
This study describes the impact of clinical, angiographic, and demographic characteristics on the long-term survival of Coronary Artery Surgery Study (CASS) patients while they were under medical treatment. Revascularization rates for the population are also provided.

METHODS AND RESULTS
All CASS patients who had not received heart surgery before enrollment (23,467 patients) were included in this survival analysis while they were under medical treatment or surveillance. Follow-up time ranged from 0 to 17 years (median, 12 years). Long-term vital status is known for 95.8% of these patients. Log-rank tests, Kaplan-Meier survival curves, and Cox proportional-hazards regression are used to describe and assess the impact of patient characteristics on survival. Characteristics that had a significant impact on survival, in order of observed explanatory power, are age, number of diseased vessels, congestive heart failure score, smoking history, ejection fraction, sex, presence of left main coronary artery disease, presence of diabetes, left ventricular wall motion score, presence of other illnesses, history of myocardial infarction, and presence of left main equivalent disease. Overall, 12-year survival for patients with zero-, one-, two- and three-vessel disease is 88%, 74%, 59%, and 40%, respectively. Twelve-year survival for patients with at least one diseased vessel and ejection fractions in the ranges of 50% to 100%, 35% to 49%, and 0% to 34% is 73%, 54%, and 21%, respectively. High myocardial jeopardy, high anginal class, and two or three proximal diseased vessels characterize the profile of patients most likely to have received surgical treatment during follow-up.

CONCLUSIONS
These results contribute to the understanding of the natural history of coronary artery disease and are also of historical interest. The poor survival of patients with three-vessel disease and low ejection fractions continues to emphasize the importance of considering revascularization for these patients.
Relation between physical training and ambulatory blood pressure in stage I hypertensive subjects. Results of the HARVEST Trial. Hypertension and Ambulatory Recording Venetia Study.
Authors: Palatini P , Graniero G R , Mormino P , Nicolosi L , Mos L , Visentin P , Pessina A C 
Published: June 2012

BACKGROUND
This study was undertaken to assess whether ambulatory blood pressure (BP) in a population of stage I hypertensive individuals was lower in the subjects performing regular exercise training.

METHODS AND RESULTS
The study was carried out in 796 young hypertensive patients (592 men) who had never been treated who took part in the HARVEST trial. The diagnosis of stage I hypertension was made on the basis of six office BP measurements. Subjects underwent noninvasive 24-hour ambulatory BP monitoring, 24-hour urine collection for catecholamine assessment, and echocardiography (n = 457). They were classified as exercisers if they reported at least one session of aerobic sports per week and as nonexercisers if they did not engage regularly in sports activities. Age (P < .0001), body mass index (P = .002), 24-hour heart rate (P < .0001), alcohol intake (P = .02), smoking (P = .02), and norepinephrine output (P = .04) were lower in the active (n = 153) than the inactive (n = 439) men. Physically active men exhibited a lower 24-hour and daytime diastolic BP than the inactive men, while there were no group differences in office BP or in nighttime diastolic BP and in ambulatory systolic BP. The between-group ambulatory diastolic BP difference remained statistically significant after adjustment for age, body mass index, alcohol intake, and smoking (P < .0001). Of the nonexercisers, 46.2% were confirmed hypertensives, compared with only 26.8% of the exercisers (P < .0001), on the basis of daytime diastolic BP. Echocardiographic left ventricular dimensional and functional indexes were similar in the two groups of men. Similar findings were shown by the 16 women who engaged in aerobic sports.

CONCLUSIONS
These data suggest that participation in aerobic sports may attenuate the risk of hypertension in young subjects whose office BP is in the stage I hypertensive range at office measurement.
The Growing Flood of Technetium-99m Myocardial Perfusion Agents
Authors: Miller D. Douglas 
Published: June 2012

“Ol’ man river, dat ol’ man river,

He must know sumpin’, but don’t say nothin’,

He just keeps rollin’, he keeps on rollin’ along.”

Ol’ Man River

—Oscar Hammerstein II
© 1927 T.B. Harms Co. Copyright renewed.
Work of the Heart Under the Effect of Induced Arterial Pressure Oscillations Studied in Intact Anesthetized Dogs
Authors: PIEPER HEINZ P. 
Published: June 2012

The arterial system of intact anesthetized dogs and a physical model, which consisted of a "heart," an elastic "arterial" reservoir, and a "peripheral resistance," have both been studied in comparison. In both systems, the volume contained in the arterial reservoir was rhythmically altered by means of a slow sinusoidal piston pump which resulted in slow oscillations of the mean arterial pressure with the arterial pressure pulsations superimposed.
It was found that in the physical model, the systolic pressure pulse was larger during the phase of rising pressure (increasing volume) than during the phase of falling pressure (decreasing volume), while in the animal the systolic pressure pulses were equal in either phase. The aortic pressure pulse of the animal was a linear function of the presystolic aortic pressure during pressure oscillation and independent of the induced volume alteration.
Recordings of the stroke output of the heart revealed that the heart of the animal adjusted its output in such a manner that the induced systolic changes of the arterial contents were quantitatively compensated. The mechanism by which this is accomplished is of particular interest, since it would also enable the heart to compensate instantaneously for physiological alterations of the volume in the arterial system as caused by changes in peripheral runoff. This mechanism of instantaneous adjustment of the stroke output can be explained on the basis of Starling's Law of the Heart if the procedure of the calculation of the external work is modified.
Diagnostic Applications of Indicator-Dilution Technics In Congenital Heart Disease
Authors: Wood Earl H. 
Published: June 2012

In summarizing the diagnostic value of the indicator-dilution technics in the study and investigation of congenital heart disease, perhaps a simple listing of the advantages and disadvantages of the technics will suffice.
The advantages are as follows: 1. The technics have a high degree of safety. In the more than 3000 cardiac patients in whom they have been utilized there have been no deaths and little or no morbidity. 2. The sensitivity of the technics for the detection and localization of right-to-left and left-to-right shunts is much superior to that of the conventional blood-gas methods. 3. Quantitative determinations of systemic and pulmonary blood flow and intrathoracic shunts by indicator-dilution methods can be made simultaneously over periods of less than 1 minute; when indicator dyes are used, these technics do not require manometrie analyses, accessory respiratory exchange studies, or active cooperation of the patient; and they are independent of foreign (anesthetic) gases in the blood. 4. The technics are versatile and can be extremely useful either for the detection and diagnosis of minimal, relatively simple defects or for the elucidation of the extremely complex types of congenital malformations. 5. The information obtained is of both a qualitative and a quantitative nature; that is, the nature and location of defects can be determined and, in addition, the magnitude and direction of flow through the defects in question as well as the levels of systemic and pulmonary blood flows can be estimated.
The disadvantages of the technics are as follows: 1. Rather complicated and sensitive recording equipment is essential. 2. Considerable technical skill is required of the persons carrying out the procedure in the placement of the necessary needles and catheters and in the proper selection of the multiple possible injection and sampling sites reached by these instruments in order to obtain the information needed to establish the diagnosis in question. 3. Correct interpretation of the diagnostic significance of the dilution curves obtained requires careful study and considerable experience by the person responsible for this phase of the investigation.
In other words, these technics entail relatively little discomfort and little danger for the patient, but require good equipment and, more important, considerable time, effort and skill on the part of the investigator and his assistants in order to obtain highly successful results.
Effect of Exercise on Blood Coagulation
Authors: Keeney Clifford E. , Laramie David W. 
Published: June 2012

Whole blood clotting time was measured before and after four different intensities and durations of exercise, using 12 male college students as subjects. The exercises consisted of a 15-minute walk on a motor-driven treadmill at 2.5 m.p.h., a 2-hour walk on the treadmill at 2.5 m.p.h., a run to near exhaustion on the treadmill at 6.25 m.p.h., and a stepping exercise on a 12-inch bench, 30 steps per minute for 15 minutes. Thromboplastin generation rate was measured before and after the stepping exercise on blood samples drawn from 14 subjects, and thrombin generation rate was similarly measured on samples drawn from 16 subjects.
No statistically significant variation was found in whole blood clotting time of samples drawn before the exercise, 1 minute after the exercise, or 15 and 30 minutes after. Neither was there any significant change in the thromboplastin generation rate of samples drawn before, 1 minute after, and 30 minutes after exercise. Ten of the 16 subjects showed no change in thrombin generation rate after exercise. However, six subjects experienced an acceleration of thrombin generation from a mean time of maximum thrombin concentration at 5.2 minutes before exercise to 4.0 minutes one minute after exercise. This difference was statistically significant.
From these data it was concluded that, in general, exercise was not followed by hypercoagulability. However, in some subjects, thrombin generation rate was increased due to undetermined factors.