bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent thrombin generation in humans during specific thrombin inhibition with hirudin.
Authors: Zoldhelyi P , Bichler J , Owen W G , Grill D E , Fuster V , Mruk J S , Chesebro J H 
Published: June 2012

BACKGROUND
The degree to which antithrombotic drugs suppress thrombin generation is unknown. Because hirudin, unlike antithrombin III, binds intravascular thrombin rapidly and selectively to yield a circulating inactive complex of 3- to 4-hour half-life, we used intravenous hirudin in humans to investigate the course of thrombin generation during and early after anticoagulation with this potent, direct antithrombin.

METHODS AND RESULTS
Intravascular thrombin was measured with an ELISA for the thrombin-hirudin complex formed during and for 18 hours after stopping a 6-hour infusion of hirudin at 0.1, 0.2, and 0.3 mg.kg-1.h-1 in three groups of six patients each. With free hirudin in 20- to 10,000-fold molar excess of thrombin and peak activated partial thromboplastin times of 2.3 to 3.0 times baseline, mean plasma thrombin-hirudin complex increased from 794 +/- 85 pg/mL (mean +/- SEM) 15 minutes after the start of the infusion to 1617 +/- 151 pg/mL at 6 hours of infusion to 2667 +/- 654 pg/mL at 24 hours. During the 24-hour observation period, plasma concentration of fragment 1.2 (the peptide released during conversion of prothrombin to thrombin) never fell below baseline but rather increased transiently during the hirudin infusion. Plasma concentrations of thrombin-antithrombin III complex (in ng/mL) decreased from 4.34 +/- 0.40 at baseline to 1.64 +/- 0.13 at 6 hours (P < .001) and gradually increased after stopping the infusion to 5.7 +/- 0.87 at 24 hours (nonsignificant compared with baseline).

CONCLUSIONS
Measurement of thrombin-hirudin complex may be used as a marker of thrombin generation in humans. Persistent accumulation of thrombin-hirudin complex and generation of fragment 1.2 during and after completion of potent anticoagulation with hirudin suggest thrombin generation is not blocked by high-affinity thrombin inhibition. The persistent formation of thrombin during declining plasma levels of hirudin may contribute to the pathogenesis of rethrombosis early after antithrombin therapy or during inadequate anticoagulation.
Mechanism of exercise hypotension in patients with ischemic heart disease. Role of neurocardiogenically mediated vasodilation.
Authors: Lele S S , Scalia G , Thomson H , Macfarlane D , Wilkinson D , Stafford W , Khafagi F , Frenneaux M 
Published: June 2012

BACKGROUND
Exercise-induced hypotension in patients with coronary artery disease (CAD) has been considered to be due to an inability to achieve an adequate increase in cardiac output to match the demands of exercise. We investigated 10 consecutive patients (9 men and 1 woman; age, 38 to 71 years; mean, 52 years) with angiographically documented CAD and exercise-induced hypotension (EIH) (BPPeak < BPRest). Ten approximately age- and sex-matched patients with documented CAD and normal exercise blood pressure response (NBP) served as control subjects.

METHODS AND RESULTS
Nine patients with EIH and all 10 control subjects underwent forearm plethysmography and radionuclide ventriculography (RNV) during semierect cycle exercise. Forearm vascular resistance (FVR) fell by 35 +/- 21% in exercise-induced hypotension patients versus an increase of 78 +/- 65% in patients with an NBP response (P < .0001). Left ventricular ejection fraction increased by 5.1 +/- 7.5% in the group with EIH versus a fall of 4.1 +/- 6.2% in the control group (P = .004). Cardiac output at peak exercise (RNV) increased by 2.2 +/- 0.89-fold in the group with EIH versus 1.49 +/- 0.47-fold in the control group (P = .04). The tenth patient in the group with EIH underwent invasive hemodynamic evaluation during erect exercise. Systolic blood pressure fell (136/80Rest to 50/40Peak) and cardiac output (Fick) tripled, whereas calculated systemic vascular resistance decreased by a factor of 10. Successful angioplasty to an isolated circumflex lesion resulted in resolution of symptoms and abnormal hemodynamic responses during exercise.

CONCLUSIONS
Abnormal vasodilation associated with a normal or even increased rather than decreased cardiac output response appears to be an important mechanism underlying EIH in some patients with CAD. In the present study, this appears to have been the dominant mechanism in 8 and contributory in 2 of the consecutive patients studied.
Prognosis of asymptomatic patients with hypertrophic cardiomyopathy and nonsustained ventricular tachycardia.
Authors: Spirito P , Rapezzi C , Autore C , Bruzzi P , Bellone P , Ortolani P , Fragola P V , Chiarella F , Zoni-Berisso M , Branzi A 
Published: June 2012

BACKGROUND
In the early 1980s, studies performed in highly selected referral patients with hypertrophic cardiomyopathy reported a strong association between the presence of brief episodes of ventricular tachycardia (VT) on ambulatory ECG monitoring and sudden death. These observations led to antiarrhythmic treatment in many patients with hypertrophic cardiomyopathy and brief episodes of VT. In recent years, however, a growing awareness of the potential arrhythmogenic effects of antiarrhythmic medications has raised doubts regarding such a therapeutic approach, particularly in less selected and lower-risk patient populations.

METHODS AND RESULTS
In the present study, we examined the prognostic significance of nonsustained VT in a population of 151 patients with hypertrophic cardiomyopathy who were asymptomatic or had only mild symptoms at the time of their initial ambulatory ECG recording. Of the 151 study patients, 42 had episodes of VT and 109 did not. The runs of VT ranged from 3 to 19 beats, with 35 patients (83%) having < 10 beats. The number of runs of VT ranged from 1 to 12 in 24 hours, with 36 patients (86%) having < or = 5 episodes of VT. Thus, in most patients, the episodes of VT were brief and infrequent. Follow-up averaged 4.8 years. Of the 151 study patients, 6 died suddenly, 3 in the group with VT and 3 in the group without VT. Two other patients, both in the group without VT, died of congestive heart failure. The total cardiac mortality rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.9% in those without VT (95% CI, 0.4% to 2.0%; P = .43). The relative risk of cardiac death for patients with VT was 1.4 compared with patients without VT (95% CI, 0.6 to 6.1). The sudden death rate was 1.4% per year in the patients with VT (95% CI, 0.4% to 3.5%) and 0.6% in those without VT (95% CI, 0.2% to 1.5%; P = .24). The relative risk of sudden death for patients with VT compared with those without VT was 2.4 (95% CI, 0.5 to 11.9). Of the 151 patients included in the study, 88 (58%) remained asymptomatic and were not treated with cardioactive medications during follow-up. Of these 88 patients, 20 were in the group with VT and 68 in the group without VT. None of these patients died.

CONCLUSIONS
Our results show that cardiac mortality is low in patients with hypertrophic cardiomyopathy who are asymptomatic or only mildly symptomatic and have brief and infrequent episodes of VT on ambulatory ECG monitoring. Our findings also suggest that brief and infrequent episodes of VT should not be considered, per se, an indication for antiarrhythmic treatment in such patients.
Cardiac hypertrophy, aortic compliance, peripheral resistance, and wave reflection in end-stage renal disease. Comparative effects of ACE inhibition and calcium channel blockade.
Authors: London G M , Pannier B , Guerin A P , Marchais S J , Safar M E , Cuche J L 
Published: June 2012

BACKGROUND
We wished to assess the respective roles of the antihypertensive and blood pressure (BP)-independent effects of antihypertensive drugs on arterial hemodynamics and left ventricular hypertrophy (LVH) in end-stage renal disease (ESRD) patients.

METHODS AND RESULTS
In a double-blind study, 24 ESRD patients with LVH were randomized to 12 months' administration of either the angiotensin-converting enzyme (ACE) inhibitor perindopril (n = 14) or the calcium channel blocker nitrendipine (n = 10). Repeated measurements of the following parameters were performed: BP (mercury sphygmomanometry), left ventricular mass (LVM, echocardiography), cardiac output (aortic cross-section and velocity integral), total peripheral resistance (cardiac output and mean BP), aortic and large-artery compliance (pulse wave velocity, Doppler flowmeter), and arterial wave reflections (augmentation index, applanation tonometry). Radioimmunoassay was used to determine plasma renin activity, aldosterone, and plasma catecholamine levels. Two-way (time-treatment) ANOVA for repeated measures was used for statistical analysis. Perindopril and nitrendipine induced significant and similar decreases in BP, total peripheral resistance (P < .001), aortic and arterial pulse wave velocities (P < .001), and arterial wave reflections (P < .01). At baseline, the two groups had LVH mostly due to increased LV end-diastolic diameter (LVEDD) (perindopril, 54.3 +/- 1.4 and nitrendipine, 54.3 +/ 2.4 mm) with near-normal mean LV wall thickness (perindopril, 11.4 +/- 0.3 and nitrendipine, 11.2 +/- 0.4 mm). A decrease in LVM was observed only in patients receiving perindopril (from 317 +/- 18 to 247 +/- 21 g) (time-treatment interaction, P = .036). Nitrendipine had no significant effect on LVM (314 +/- 29 versus 286 +/- 32 g). The decrease in LVM observed with perindopril was associated with a reduction in LVEDD (49.9 +/- 1.6 versus 54.3 +/- 1.4 mm after 12 months) (time-treatment interaction, P = .04), while the mean LV wall thickness was unchanged (11.4 +/- 0.3 versus 10.5 +/- 0.5 mm). Cardiac alterations were not correlated with changes in BP or with alterations in plasma renin activity or aldosterone or catecholamine levels.

CONCLUSIONS
In ESRD patients with LVH, ACE inhibition decreases LVM independently of its antihypertensive effect and of associated alterations in arterial hemodynamics. The decrease in LVM was due primarily to a decrease in LV volume, which may have resulted in these patients from chronic volume overload.
Relation of smoking with carotid artery wall thickness and stenosis in older adults. The Cardiovascular Health Study. The Cardiovascular Health Study (CHS) Collaborative Research Group.
Authors: Tell G S , Polak J F , Ward B J , Kittner S J , Savage P J , Robbins J 
Published: June 2012

BACKGROUND
Cigarette smoking has been associated with increased risk of atherosclerotic diseases in hospital-based studies and in studies of middle-aged populations but not in population-based studies of older adults with and without clinical cardiovascular disease.

METHODS AND RESULTS
We investigated the relation of smoking to carotid artery atherosclerotic disease, expressed as intimal-medial wall thickness and arterial lumen narrowing (stenosis) measured by ultrasound. Subjects were 5116 older adults participating in the baseline examination of the Cardiovascular Health Study, a community-based study of cardiovascular diseases in older age. With increased smoking there was significantly greater internal and common carotid wall thickening and internal carotid stenosis: current smokers > former smokers > never-smokers; for instance, the unadjusted percent stenosis was 24%, 20%, and 16%, respectively (P < .0001). A significant dose-response relation was seen with pack-years of smoking. These findings persisted after adjusting for other cardiovascular risk factors and were also confirmed when analyses were restricted to those without prevalent cardiovascular disease. The difference in internal carotid wall thickness between current smokers and nonsmokers was greater than the difference associated with 10 years of age among never-smoking participants (0.39 mm versus 0.31 mm). Among all participants, the prevalence of clinically significant (> or = 50%) internal carotid stenosis increased from 4.4% in never-smokers to 7.3% in former smokers to 9.5% in current smokers (P < .0001).

CONCLUSIONS
These findings extend previous reports of a positive relation between smoking and carotid artery disease to a population-based sample of older adults using several different indicators of atherosclerotic disease.
Role of arterial chemoreceptors in mediating the effects of endogenous adenosine on sympathetic nerve activity.
Authors: Engelstein E D , Lerman B B , Somers V K , Rea R F 
Published: June 2012

BACKGROUND
Exogenous adenosine has been shown to increase muscle sympathetic nerve activity (MSNA), blood pressure, heart rate, and ventilation in conscious humans, effects attributed to peripheral chemoreceptor activation.

METHODS AND RESULTS
To determine whether endogenous adenosine has similar effects and whether they are mediated through chemoreceptor activation, we examined the effects of dipyridamole, an inhibitor of adenosine reuptake, on sympathetic nerve activity and ventilation. Twenty studies were conducted on separate days in 15 healthy volunteers. We examined responses to dipyridamole 0.56 mg/kg during room air breathing (n = 7), during hyperoxia (100% O2, n = 6), and during room air breathing after pretreatment with aminophylline (n = 7). During room air breathing, dipyridamole increased MSNA from 231 +/- 42 to 504 +/- 136 U/min, heart rate from 65 +/- 3.8 to 96 +/- 4.7 beats per minute, and systolic blood pressure from 129 +/- 3.5 to 140 +/- 4.8 mm Hg; central venous pressure decreased from 5.5 +/- 0.4 to 4.5 +/- 0.3 mm Hg (P < .01), and minute ventilation increased from 7.8 +/- 0.6 to 9.1 +/- 0.5 L/min (P < .01). During peripheral chemoreceptor suppression (with hyperoxia), there was a dissociation of the effects of dipyridamole on ventilation and sympathoexcitation. Effects on ventilation were attenuated, but sympathoexcitatory effects were not. Pretreatment with aminophylline, an adenosine receptor antagonist, either abolished (blood pressure, minute ventilation, and end-tidal CO2) or markedly attenuated (MSNA and heart rate) the effects of dipyridamole during room air breathing.

CONCLUSIONS
Augmentation of endogenous adenosine with dipyridamole increases sympathetic nerve activity and ventilation in conscious humans. The ventilatory effects of endogenous adenosine are mediated predominantly by chemoreceptor activation, but the sympathetic and hemodynamic responses to endogenous adenosine are probably mediated by an additional afferent mechanism that is independent of peripheral chemoreceptor activation.
Low-dose, beta-particle emission from 'stent' wire results in complete, localized inhibition of smooth muscle cell proliferation.
Authors: Fischell T A , Kharma B K , Fischell D R , Loges P G , Coffey C W , Duggan D M , Naftilan A J 
Published: June 2012

BACKGROUND
Restenosis after catheter-based revascularization has been demonstrated to be primarily caused by medial and/or intimal smooth muscle cell (SMC) proliferation. The objective of this study was investigate the ability of local emission of beta-particles from a 32P-impregnated titanium "stent" wire source to inhibit vascular SMC and endothelial cell proliferation in cell culture and to determine the dose-response characteristics of this inhibition.

METHODS AND RESULTS
A series of experiments were performed using 0.20-mm-diameter titanium wires that were impregnated with varying low concentrations of 32P (activity range, 0.002 to 0.06 microCi/cm wire, n = 47) or 31P (nonradioactive control, n = 28) in cultures of rat and human aortic SMCs and in cultured bovine aortic endothelial cells. The zone of complete cell growth inhibition (in millimeters from stent wire) was measured using light microscopy in the cultures exposed to the radioactive (32P) or control (31P) wires at 6 and 12 days after plating. In both rat and human SMC cultures there was a distinct 5.5- to 10.6-mm zone of complete SMC inhibition at wire activity levels > or = 0.006 microCi/cm. In contrast, there was no zone of inhibition surrounding the control (31P impregnated) wires (P < .001 versus 32P wires at all wire activities > or = 0.006 microCi/cm for human and rat SMCs). Proliferating bovine endothelial cells were more radioresistant than SMCs, with no zone of inhibition observed at wire activity levels up to 0.019 microCi/cm (P < .001 versus SMCs at 0.006 microCi/cm and 0.019 microCi/cm).

CONCLUSIONS
We conclude that very low doses of beta-particle emission from a 32P-impregnated stent wire (activity levels as low as 0.006 microCi/cm of wire) completely inhibit the growth and migration of both rat and human SMCs within a range of 5.5 to 10.6 mm from the wire. Endothelial cells appear to be much more radioresistant than SMCs. These data suggest that an intra-arterial stent impregnated with a low concentration of 32P may have a salutary effect on the restenosis process. Whether this approach can be used successfully and safely to inhibit restenosis in vivo and in the clinical setting is under investigation.
Geometric remodeling is not the principal pathogenetic process in restenosis after balloon angioplasty. Evidence from correlative angiographic-histomorphometric studies of atherosclerotic arteries in rabbits.
Authors: Gertz S D , Gimple L W , Banai S , Ragosta M , Powers E R , Roberts W C , Perez L S , Sarembock I J 
Published: June 2012

BACKGROUND
Restenosis after balloon angioplasty of coronary arteries is thought to be a proliferative response of the arterial wall to injury. Recently, it has been suggested that geometric remodeling of the arterial wall, rather than intimal fibromuscular hyperplasia, may be the major pathophysiological mechanism underlying restenosis. In this study, we evaluated the relative contribution of a geometric decrease in arterial size versus neointimal growth to luminal narrowing associated with restenosis after balloon angioplasty of atherosclerotic femoral arteries in rabbits.

METHODS AND RESULTS
Focal femoral atherosclerosis was induced by endothelial desiccation injury followed by a 2% cholesterol diet. After 1 month on the high cholesterol diet, the animals were subjected to one of four strategies: (1) balloon angioplasty, (2) balloon angioplasty followed by treatment with the factor Xa inhibitor antistasin, (3) combined laser and balloon angioplasty, or (4) no angioplasty. Animals were killed 2 hours or 28 days after angioplasty, and excised femoral artery segments were prepared for histomorphometric analysis. Angiography was performed serially before and immediately after angioplasty and before the animals were killed. An initial postprocedural gain in luminal diameter at sites of angioplasty was followed by a significant reduction in diameter by angiography and a significant increase in luminal cross-sectional area narrowing by plaque by histomorphometry 28 days after angioplasty compared to adjacent nonangioplastied segments of the same arteries, to nonangioplastied control arteries, or to angioplastied segments of animals treated with the factor Xa inhibitor antistasin. By contrast, the overall arterial size (cross-sectional area bounded by the external elastic lamina) at sites of restenosis was not significantly different from adjacent nonangioplastied segments in the majority of arteries excised at 28 days, and the mean overall arterial size at sites of restenosis was not significantly different from corresponding segments of nonangioplastied control arteries or from angioplastied segments of animals treated with antistasin. In the minority of angioplastied arteries in which the arterial size did change, most got larger.

CONCLUSIONS
Geometric remodeling resulting in a decrease in overall cross-sectional arterial size does not appear to be the principal pathogenetic mechanism for restenosis after balloon angioplasty with or without laser in this experimental model.
Effect of myocardial fiber direction on epicardial potentials.
Authors: Taccardi B , Macchi E , Lux R L , Ershler P R , Spaggiari S , Baruffi S , Vyhmeister Y 
Published: June 2012

BACKGROUND
Understanding the relations between the architecture of myocardial fibers, the spread of excitation, and the associated ECG signals is necessary for addressing the forward problem of electrocardiography, that is, predicting intracardiac and extracardiac ECGs from known intracardiac activity. So far, these relations have been studied experimentally only in small myocardial areas. In this study, we tested the hypothesis that potential distributions measured over extensive epicardial regions during paced beats reflect the direction of superficial and intramural fibers through which excitation is spreading in both the initial and later stages of ventricular excitation. We also tried to establish whether the features of the epicardial potential distribution that correlate with fiber direction vary as a function of pacing site, intramural pacing depth, and time elapsed after the stimulus. An additional purpose was to compare measured epicardial potentials with recently published numerical simulations depicting the three-dimensional spread of excitation in the heart muscle and the associated potential fields.

METHODS AND RESULTS
The hearts of 18 mongrel dogs were exposed and 182 to 744 unipolar electrograms were recorded from epicardial electrode arrays (2.3 x 3.0 to 6.5 x 6.5 cm). Hearts were paced at various intramural depths through an intramural needle. The overall number of pacing sites in 18 dogs was 241. Epicardial potential distributions, electrographic waveforms, and excitation time maps were displayed, and fiber directions in the ventricular wall underlying the electrodes were determined histologically. During the early stages of ventricular excitation, the position of the epicardial maxima and minima revealed the orientation of myocardial fibers near the pacing site in all cases of epicardial and intramural pacing and in 60% of cases of endocardial or subendocardial pacing. During later stages of propagation, the rotation and expansion of the positive areas correlated with the helical spread of excitation through intramurally rotating fibers. Marked asymmetry of potential patterns probably reflected epicardial-endocardial obliqueness of intramural fibers. Multiple maxima appeared in the expanding positive areas.

CONCLUSIONS
For 93% of pacing sites, results verified our hypothesis that epicardial potential patterns elicited by ventricular pacing reflect the direction of fibers through which excitation is spreading during both the initial and later stages of propagation. Epicardial potential distributions provided information on the site of origin and subsequent helical spread of excitation in an epicardial-endocardial, endocardial-epicardial, or double direction. Results were in agreement with previously published numerical simulations except for the asymmetry and fragmentation of the positive areas.
Some Aspects of Occlusive Renal Arterial Disease in Man
Authors: Dustan Harriet P. 
Published: June 2012

A review of the past six years' experience with the surgical treatment of hypertension associated with occlusive renal arterial disease has shown that in about 60 per cent of patients diastolic hypertension remitted, and in about 16 per cent arterial pressure was greatly reduced. In a small group of patients not operated upon, antihypertensive drugs were found to be as effective as in patients with essential hypertension; this suggests a neurogenic component in this type of renal hypertension.
Revascularization procedures in patients with unilateral renal arterial stenosis usually lessened disparities in glomerular filtration rate of the two kidneys but did not eliminate them. Postoperatively, solute and water excretions of the repaired kidney usually exceeded those of the unaffected side even though preoperatively they had been much less.
In a few patients, information concerning the natural history of renal arterial diseases shows that atherosclerosis need not necessarily cause progressive stenosis over periods as long as one year, and that the nonatherosclerotic lesions, segmental mural fibrosis and intimal sclerosis, once established, can exist without apparent change for as long as three years.