bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antithrombotic therapy for deep arterial injury by angioplasty. Efficacy of common platelet inhibition compared with thrombin inhibition in pigs.
Authors: Lam J Y , Chesebro J H , Steele P M , Heras M , Webster M W , Badimon L , Fuster V 
Published: June 2012

BACKGROUND
Platelet-thrombus formation is a complication of arterial wall deep injury by balloon angioplasty that may lead to acute arterial occlusion and may contribute to restenosis.

METHODS AND RESULTS
Because common platelet-inhibitor drugs with a heparin bolus (100 units/kg) may be effective in inhibiting platelet-thrombus formation after arterial angioplasty, these were compared with a bolus of heparin alone (control), the specific thrombin inhibitor hirudin (1.0 mg/kg), and saline (hirudin control) in normal pigs after angioplasty of the common carotid arteries. In the presence of deep arterial wall injury (injury exposing the media), indium-111-labeled platelet deposition (x 10(6)/cm2) was 68.8 +/- 12.3 and 48.1 +/- 16.9 in the control animals. This was significantly reduced by pretreatment with low-dose aspirin (1 mg/kg/day), by high-dose aspirin (20 mg/kg/day) plus dipyridamole, and especially by thrombin inhibition with hirudin. Treatment regimens with aspirin alone (20 mg/kg/day), dipyridamole alone, or sulfinpyrazone were ineffective. Likewise, the incidence of mural thrombosis was 75% and 80% in deeply injured arteries of controls and was significantly reduced to 46% with aspirin plus dipyridamole, 25% with low-dose aspirin, and 0% with hirudin. The incidence of mural thrombosis was unchanged with high-dose aspirin (69%), dipyridamole (90%), or sulfinpyrazone (92%). This mural thrombosis could not be identified by angiography. In the presence of mild injury (deendothelialization), platelet deposition was low (less than 10 x 10(6)/cm2, a single layer) and was not changed by any therapy, including hirudin.

CONCLUSIONS
These therapies do not affect platelet adhesion to deeply or mildly injured artery. These data suggest a greater role for thrombin inhibition than with thromboxane or cyclooxygenase inhibition in the pathogenesis of platelet-rich mural thrombosis after deep injury during angioplasty. Antithrombotic therapy for arterial thrombosis by thrombin inhibition appears promising.
Left ventricular pressure-volume and Frank-Starling relations in endurance athletes. Implications for orthostatic tolerance and exercise performance.
Authors: Levine B D , Lane L D , Buckey J C , Friedman D B , Blomqvist C G 
Published: June 2012

BACKGROUND
Endurance athletes have a high incidence of orthostatic intolerance. We hypothesized that this is related to an abnormally large decrease in left ventricular end-diastolic volume (LVEDV) and stroke volume (SV) for any given decrease in filling pressure.

METHODS AND RESULTS
We measured pulmonary capillary wedge (PCW) pressure (Swan-Ganz catheter), LVEDV (two-dimensional echocardiography), and cardiac output (C2H2 rebreathing) during lower body negative pressure (LBNP, -15 and -30 mm Hg) and rapid saline infusion (15 and 30 ml/kg) in seven athletes and six controls (VO2max, 68 +/- 7 and 41 +/- 4 ml/kg/min). Orthostatic tolerance was determined by progressive LBNP to presyncope. Athletes had steeper slopes of their SV/PCW pressure curves than nonathletes (5.5 +/- 2.7 versus 2.7 +/- 1.5 ml/mm Hg, p less than 0.05). The slope of the steep, linear portion of this curve correlated significantly with the duration of LBNP tolerance (r = 0.58, p = 0.04). The athletes also had reduced chamber stiffness (increased chamber compliance) expressed as the slope (k) of the dP/dV versus P relation (chamber stiffness, k = 0.008 +/- 0.004 versus 0.031 +/- 0.004, p less than 0.005; chamber compliance, 1/k = 449.8 +/- 283.8 versus 35.3 +/- 4.3). This resulted in larger absolute and relative changes in end-diastolic volume over an equivalent range of filling pressures.

CONCLUSIONS
Endurance athletes have greater ventricular diastolic chamber compliance and distensibility than nonathletes and thus operate on the steep portion of their Starling curve. This may be a mechanical, nonautonomic cause of orthostatic intolerance.
Left ventricular hypertrophy associated with chronic cocaine abuse.
Authors: Brickner M E , Willard J E , Eichhorn E J , Black J , Grayburn P A 
Published: June 2012

BACKGROUND
This study was performed to determine whether chronic cocaine abuse is associated with left ventricular hypertrophy in humans.

METHODS AND RESULTS
A consecutive series of 40 chronic cocaine abusers 23-44 years old who were enrolled in an inpatient drug rehabilitation program were considered for the study. Subjects with elevated resting blood pressure (n = 4) or a history of hypertension (n = 3) were excluded. Technically adequate two-dimensional echocardiograms were obtained in 30 cocaine abusers and 30 age- and race-matched normal control subjects. All subjects were men, and the groups were similar with regard to resting blood pressure, height, weight, and body surface area. All echocardiograms were read in blinded fashion, and left ventricular mass was calculated by the area-length method. Left ventricular cavity dimensions and wall motion were normal in all subjects. Left ventricular mass index was higher in the cocaine group (103 +/- 24 versus 77 +/- 14 g/m2, p = 0.0001). Posterior wall thickness was increased (1.2 cm or more) in 13 cocaine abusers (43%) compared with four controls (p = 0.0099).

CONCLUSIONS
Chronic cocaine abuse is associated with increased left ventricular mass index and wall thickness. Left ventricular hypertrophy may provide a substrate facilitating the development of myocardial ischemia and/or arrhythmias in cocaine abusers.
The long QT syndrome. Prospective longitudinal study of 328 families.
Authors: Moss A J , Schwartz P J , Crampton R S , Tzivoni D , Locati E H , MacCluer J , Hall W J , Weitkamp L , Vincent G M , Garson A 
Published: June 2012

BACKGROUND
The Long QT Syndrome (LQTS) is an infrequently occurring familial disorder in which affected individuals have electrocardiographic QT interval prolongation and a propensity to ventricular tachyarrhythmic syncope and sudden death. We prospectively investigated the clinical characteristics and the long-term course of 3,343 individuals from 328 families in which one or more members were identified as affected with LQTS (QTc greater than 0.44 sec1/2).

METHODS AND RESULTS
The first member of a family to be identified with LQTS, the proband, was usually brought to medical attention because of a syncopal episode during childhood or teenage years. Probands (n = 328) were younger at first contact (age 21 +/- 15 years), more likely to be female (69%), and had a higher frequency of preenrollment syncope or cardiac arrest with resuscitation (80%), congenital deafness (7%), a resting heart rate less than 60 beats/min (31%), QTc greater than or equal to 0.50 sec1/2 (52%), and a history of ventricular tachyarrhythmia (47%) than other affected (n = 688) and unaffected (n = 1,004) family members. Arrhythmogenic syncope often occurred in association with acute physical, emotional, or auditory arousal. The syncopal episodes were frequently misinterpreted as a seizure disorder. By age 12 years, 50% of the probands had experienced at least one syncopal episode or death. The rates of postenrollment syncope (one or more episodes) and probable LQTS-related death (before age 50 years) for probands (n = 235; average follow-up 54 months per patient) were 5.0% per year and 0.9% per year, respectively; these event rates were considerably higher than those observed among affected and unaffected family members.

CONCLUSIONS
Among 232 probands and 1,264 family members with prospective follow-up, three factors made significant independent contributions to the risk of subsequent syncope or probable LQTS-related death before age 50 years, whichever occurred first (Cox hazard ratio; 95% confidence limits): 1) QTc (1.052; 1.017, 1.088), 2) history of cardiac event (3.1; 1.3, 7.2), and 3) heart rate (1.017; 1.004, 1.031). The findings from this prospective longitudinal study highlight the clinical features, risk factors, and course of LQTS.
Adenosine as a vasodilator in primary pulmonary hypertension.
Authors: Morgan J M , McCormack D G , Griffiths M J , Morgan C J , Barnes P J , Evans T W 
Published: June 2012

BACKGROUND
The acute administration of vasodilator drugs to patients with primary pulmonary hypertension has been advocated to identify those with reversible pulmonary vasoconstriction. Unfortunately, the usefulness of the drugs currently available is limited by accompanying systemic hypotension. A vasodilator with effects confined to the pulmonary circulation would therefore be advantageous in such patients.

METHODS AND RESULTS
The purine nucleoside adenosine was infused into the pulmonary artery in seven patients with primary pulmonary hypertension (baseline pulmonary vascular resistance [PVR], 442-1,295 dyne/cm/sec-5) to determine its effect on PVR. In all patients, there was a dose-dependent and significant reduction (mean maximal percent decrease from baseline, 38.9%; p less than 0.001) in PVR mediated through a decrease in pulmonary artery pressure and an increase in cardiac output. Systemic vascular resistance (SVR) also decreased, but the ratio of PVR to SVR decreased (maximal mean percent decrease from baseline) by 10.5% (p less than 0.025), indicating that adenosine has a preferential vasodilator effect on the pulmonary circulation when administered in this manner.

CONCLUSIONS
Because of its pharmacokinetic and vasodilator properties, adenosine may have a specific role in the investigation of primary pulmonary hypertension.
Proximal regulatory domains of rat atrial natriuretic factor gene.
Authors: Rosenzweig A , Halazonetis T D , Seidman J G , Seidman C E 
Published: June 2012

BACKGROUND
At least three cis-acting regulatory elements are required for expression of the rat atrial natriuretic factor (ANF) gene. One distal cis-acting regulatory element lies more than 640 base pairs from the transcription initiation site.

METHODS AND RESULTS
In this report, we identify two other proximal regulatory elements that lie within 609 base pairs of the transcription initiation site. One proximal regulatory element contains an activator protein-1 (AP-1)-like binding site and is recognized by the AP-1 protein, the c-fos/c-jun proto-oncogene heterodimer in vitro. The second regulatory element contains a cyclic AMP-responsive element (CRE)-like recognition site.

CONCLUSIONS
In vitro binding of the c-fos/c-jun heterodimer to ANF gene sequences suggests that the heterodimer may play a role in the regulation of gene transcription in vivo. This observation may also explain the correlation between c-fos/c-jun expression and ventricular ANF gene expression found in hypertrophic states. Nuclear extracts from normal cardiocytes contain proteins that bind these regulatory elements but do not appear to bind at the AP-1 site, suggesting that the levels of fos/jun heterodimer in nonhypertrophied cardiocytes are quite low.
Repolarization inhomogeneities in ventricular myocardium change dynamically with abrupt cycle length shortening.
Authors: Rosenbaum D S , Kaplan D T , Kanai A , Jackson L , Garan H , Cohen R J , Salama G 
Published: June 2012

BACKGROUND
In single heart cells, abrupt changes in stimulation rate elicit complex alterations in repolarization. The effects of rate change on dispersion of repolarization, however, have not been well characterized.

METHODS AND RESULTS
To determine the effects of abrupt cycle length (CL) shortening on spatial inhomogeneity of repolarization in a syncytium of ventricular cells, 124 action potentials were simultaneously recorded from Langendorff-perfused guinea pig hearts using high-resolution optical mapping with voltage-sensitive dye. The distribution of ventricular action potential durations (APDs) mapped during each cardiac cycle was used to calculate mean APD and repolarization dispersion index (DI), defined as the variance of the distribution. After abruptly shortening CL from 500 to 300 msec, mean APD declined exponentially in normoxic controls (by 23 +/- 3 msec, p less than 0.0001). This response was characterized by beat-to-beat oscillations of APD that were synchronized at all ventricular sites. After 30 minutes of hypoxia, mean APD decreased from 175.0 +/- 13.3 to 76 +/- 25.7 msec. However, during hypoxia, abrupt CL shortening lowered mean APD by only an additional 6 +/- 6 msec, and APD oscillations were no longer synchronized throughout the ventricle. In controls, beat-to-beat DI decreased significantly (-51.0 +/- 6.8%, p less than 0.01) by the sixth post-CL shortening beat and then recovered (by 15-20 beats). In contrast, DI failed to decrease during hypoxia (+7.1 +/- 23%). Two mechanisms for the transient decline of DI in controls were identified: synchronous APD oscillations and transient diminution of the apical-to-basal ventricular APD gradient.

CONCLUSIONS
These data demonstrate that inhomogeneity of ventricular repolarization, as measured by DI, changes dynamically with CL shortening. Furthermore, the hypoxic ventricle does not attenuate DI after abrupt CL shortening and thereby lacks a physiological response expected to diminish vulnerability to arrhythmias.
Effects of dietary omega 3 fatty acids on vascular contractility in preanoxic and postanoxic aortic rings.
Authors: Malis C D , Leaf A , Varadarajan G S , Newell J B , Weber P C , Force T , Bonventre J V 
Published: June 2012

BACKGROUND
Vasomotor reactivity may contribute to the pathophysiology of ischemic injury. The atherosclerotic vessel may be particularly susceptible to vasoconstriction because of the damaged endothelial layer with resultant loss of vasodilatory factors. While dietary omega 3 fatty acids have been proposed to protect against vascular occlusion, it is not clear to what extent this results from alterations in the function of platelets or from changes intrinsic to the blood vessel itself.

METHODS AND RESULTS
The effects of dietary supplementation with fish oils on vascular contractility were examined in endothelialized and de-endothelialized aortic rings under pre- and postanoxic conditions. De-endothelialization was defined functionally by the loss of acetylcholine-induced vasodilation in norepinephrine-preconstricted aortic rings from rats fed normal rat chow. Three groups of rats were fed diets containing either 20% menhaden oil or 20% beef tallow, both supplemented with 3% corn oil or 23% corn oil for longer than 4 weeks. All animals received vitamin E. Under well-oxygenated conditions, de-endothelialized aortic rings from rats fed fish oil and corn oil contracted to similar extents with norepinephrine and vasopressin and less than rings from rats fed beef tallow. Endothelialized (intact) and de-endothelialized rings from rats fed fish oil relaxed more in response to acetylcholine than rings from rats fed beef tallow and corn oil. After anoxic exposure and reoxygenation, KCl-induced contraction of intact rings from rats fed fish oil and corn oil was similar and less than rings from rats fed beef tallow. Intact and de-endothelialized rings from rats fed fish oil relaxed more to acetylcholine than did rings from rats fed beef tallow and corn oil.

CONCLUSIONS
Under preanoxic or postanoxic conditions, rings from rats fed fish oil and corn oil contracted less than rings from rats fed beef tallow. The relaxation response to acetylcholine, however, was greater in rings from rats fed fish oil than from rats fed either corn oil or beef tallow. These vascular effects of fish oil feeding may result in increased blood flow to ischemic and reperfused tissues in vivo.
Relative importance of thrombin compared with plasmin-mediated platelet activation in response to plasminogen activation with streptokinase.
Authors: Winters K J , Santoro S A , Miletich J P , Eisenberg P R 
Published: June 2012

BACKGROUND
Platelet activation occurs in vivo during pharmacologic thrombolysis and may contribute to recurrent thrombosis. Plasmin does not directly activate platelets except at high concentrations; thus, the mechanisms for platelet activation during thrombolysis remain undefined. Increases in thrombin activity also occur in patients treated with fibrinolytic agents and may contribute to activation of platelets. We have shown that one mechanism for increased thrombin activity is activation of the coagulation system by plasmin.

METHODS AND RESULTS
In the present study we sought to determine whether activation of platelets in response to pharmacologic activation of plasminogen in plasma is due primarily to plasmin or mediated by increased thrombin activity. Platelet-rich citrated plasma (PRP) was recalcified and incubated with 1,000 IU/ml of streptokinase or 1.0 caseinolytic units/ml of plasmin. Concentrations of fibrinopeptide A, a marker of thrombin activity, increased markedly over 10 minutes in plasma incubated with streptokinase or plasmin, but not in PRP incubated without plasminogen activator. Platelet activation characterized by the secretion of 14C-serotonin occurred within 2-4 minutes after thrombin activity increased. In stirred recalcified PRP, platelet aggregation was accelerated from 3.6 +/- 0.5 to 2.5 +/- 0.3 minutes (p less than 0.01) when incubated with 1,000 IU/ml of streptokinase. Leupeptin and aprotinin, inhibitors of plasmin activity, markedly attenuated platelet activation in response to pharmacologic activation of plasminogen. However, inhibition of thrombin with heparin, hirudin, or D-Phe-D-Pro-L-Arg-chloromethylketone was more effective in inhibiting the acceleration of platelet activation induced by plasminogen activation, despite the elaboration of plasmin activity.

CONCLUSIONS
Activation of platelets during coronary thrombolysis may be due in part to increased procoagulant activity induced by plasminogen activation as well as other factors that promote platelet activation in vivo.
Altered skeletal muscle metabolic response to exercise in chronic heart failure. Relation to skeletal muscle aerobic enzyme activity.
Authors: Sullivan M J , Green H J , Cobb F R 
Published: June 2012

BACKGROUND
Exertional fatigue, which frequently limits exercise in patients with chronic heart failure, is associated with early anaerobic metabolism in skeletal muscle. The present study was designed to examine the skeletal muscle metabolic response to exercise in this disorder and determine the relation of reduced muscle blood flow and skeletal muscle biochemistry and histology to the early onset of anaerobic metabolism in patients.

METHODS AND RESULTS
We evaluated leg blood flow, blood lactate, and skeletal muscle metabolic responses (by vastus lateralis biopsies) during upright bicycle exercise in 11 patients with chronic heart failure (ejection fraction 21 +/- 8%) and nine normal subjects. In patients compared to normal subjects, peak exercise oxygen consumption was decreased (13.0 +/- 3.3 ml/kg/min versus 30.2 +/- 8.6 ml/kg/min, p less than 0.01), whereas peak respiratory exchange ratio and femoral venous oxygen content were not different (both p greater than 0.25), indicating comparable exercise end points. At rest in patients versus normals, there was a reduction in the activity of hexokinase (p = 0.08), citrate synthetase (p less than 0.02), succinate dehydrogenase (p = 0.0007), and 3-hydroxyacyl CoA dehydrogenase (p = 0.04). In patients, leg blood flow was decreased at rest, submaximal, and maximal exercise when compared to normal subjects (all p less than 0.05), and blood lactate accumulation was accelerated. In patients, during submaximal exercise blood lactate levels were not closely related to leg blood flow but were inversely related to rest citrate synthetase activity in skeletal muscle (r = -0.74, p less than 0.05). At peak exercise there were no intergroup differences in skeletal muscle glycolytic intermediates, adenosine nucleotides, or glycogen, whereas in patients compared to normal subjects less lactate accumulation and phosphocreatine depletion were noted (both p less than 0.05), suggesting that factors other than the magnitude of phosphocreatine depletion or lactate accumulation may influence skeletal muscle fatigue in this disorder.

CONCLUSIONS
The results of the present study suggest that in patients with chronic heart failure reduced aerobic activity in skeletal muscle plays an important role in mediating the early onset of anaerobic metabolism during exercise. Our findings are consistent with the concept that reduced aerobic enzyme activity in skeletal muscle is, in part, responsible for determining exercise tolerance and possibly the response to chronic intervention in patients with chronic heart failure.
Serial long-term assessment of the natural history of asymptomatic patients with chronic aortic regurgitation and normal left ventricular systolic function.
Authors: Bonow R O , Lakatos E , Maron B J , Epstein S E 
Published: June 2012

BACKGROUND
Many asymptomatic patients with aorta regurgitation and normal left ventricular systolic function remain clinically stable for many years, but others ultimately develop symptoms or left ventricular dysfunction and require operation. To identify indexes of left ventricular function predictive of symptomatic and functional deterioration during the long-term course of asymptomatic patients, we studied 104 asymptomatic patients with chronic severe aortic regurgitation and normal left ventricular ejection fraction at rest.

METHODS AND RESULTS
Serial echocardiographic (average, 7.8 per patient) and radionuclide angiographic (average, 5.0 per patient) studies were obtained over a mean follow-up period of 8 years (range, 2-16 years). By Kaplan-Meier life table analysis, 58 +/- 9% of patients remained asymptomatic with normal ejection fraction at 11 years, an average attrition rate of less than 5% per year; two patients died suddenly, four developed asymptomatic left ventricular dysfunction, and 19 underwent operation because symptoms developed. By univariate Cox regression analysis, many variables on initial study were associated with death, ventricular dysfunction, or symptoms, including age, left ventricular end-systolic dimension and end-diastolic dimension, fractional shortening, and both rest and exercise ejection fraction (all p less than 0.001). The average rates of change of rest ejection fraction, fractional shortening, and end-systolic dimension were also associated with death or symptoms by univariate Cox analysis (all p less than 0.01). However, when all variables were included in a multivariate Cox analysis, only age (p less than 0.05), initial end-systolic dimension (p less than 0.001), and rate of change in end-systolic dimension and rest ejection fraction during serial studies (both p less than 0.05) predicted outcome.

CONCLUSIONS
Thus, in addition to indexes of left ventricular function determined on initial evaluation, serial long-term changes in systolic function identify patients likely to develop symptoms and require operation. Patients have a higher risk of symptomatic deterioration if there is progressive change in end-systolic dimension or resting ejection fraction during the course of serial studies.