bluuebunny/crossref_metadata_2025_split huggingface dataset:
Platelet cyclic GMP. A potentially useful indicator to evaluate the effects of nitroglycerin and nitrate tolerance.
Authors: Watanabe H , Kakihana M , Ohtsuka S , Enomoto T , Yasui K , Sugishita Y 
Published: June 2012

BACKGROUND
The present study was designed to investigate the intracellular production of cyclic GMP (cGMP) in platelets in response to nitroglycerin and to determine the potential clinical value of platelet cGMP as an indicator of the effects of nitroglycerin and nitrate tolerance.

METHODS AND RESULTS
Platelet cGMP levels and the diameters of the coronary arteries before and 2 minutes after intracoronary injection of 200 micrograms nitroglycerin were measured in 15 patients who had previously received nitrates (nitrates group) and in 16 who had not received any nitrates (no-nitrates group). Platelet cGMP levels increased significantly after nitroglycerin injection in the two groups, but plasma cGMP levels and plasma atrial natriuretic peptide levels did not change. The percent increase in platelet cGMP levels and the percent dilatation of the left anterior descending (LAD) and left circumflex (LCx) coronary arteries after nitroglycerin injection were higher in the no-nitrates group than in the nitrates group (platelet cGMP levels: artery, 74.2 +/- 18.3% versus 11.5 +/- 4.2%, P < .01; vein, 73.6 +/- 22.9% versus 9.0 +/- 3.1%, P < .01; coronary dilatation: LAD, 46.7 +/- 6.0% versus 9.9 +/- 2.5%, P < .01, LCx, 51.2 +/- 8.7% versus 6.1 +/- 3.0%, P < .01). The percent increase in platelet cGMP levels was significantly correlated with the percent dilatation of the coronary arteries (LAD: r = .90, P < .01; LCx: r = .92, P < .01) in the no-nitrates group and not in the nitrates group.

CONCLUSIONS
These results indicate that platelet cGMP can be used as an indicator for in situ evaluation of nitroglycerin effects and that patients who have received nitrates develop nitrate tolerance, which affects intracellular production of cGMP and vasodilation in the response to nitroglycerin.
Influence of cigarette smoking on human autonomic function.
Authors: Niedermaier O N , Smith M L , Beightol L A , Zukowska-Grojec Z , Goldstein D S , Eckberg D L 
Published: June 2012

BACKGROUND
Although cigarette smoking is known to lead to widespread augmentation of sympathetic nervous system activity, little is known about the effects of smoking on directly measured human sympathetic activity and its reflex control.

METHODS AND RESULTS
We studied the acute effects of smoking two research-grade cigarettes on muscle sympathetic nerve activity and on arterial baroreflex-mediated changes of sympathetic and vagal neural cardiovascular outflows in eight healthy habitual smokers. Measurements were made during frequency-controlled breathing, graded Valsalva maneuvers, and carotid baroreceptor stimulation with ramped sequences of neck pressure and suction. Smoking provoked the following changes: Arterial pressure increased significantly, and RR intervals, RR interval spectral power at the respiratory frequency, and muscle sympathetic nerve activity decreased. Plasma nicotine levels increased significantly, but plasma epinephrine, norepinephrine, and neuropeptide Y levels did not change. Peak sympathetic nerve activity during and systolic pressure overshoots after Valsalva straining increased significantly in proportion to increases of plasma nicotine levels. The average carotid baroreceptor-cardiac reflex relation shifted rightward and downward on arterial pressure and RR interval axes; average gain, operational point, and response range did not change.

CONCLUSIONS
In habitual smokers, smoking acutely reduces baseline levels of vagal-cardiac nerve activity and completely resets vagally mediated arterial baroreceptor-cardiac reflex responses. Smoking also reduces muscle sympathetic nerve activity but augments increases of sympathetic activity triggered by brief arterial pressure reductions. This pattern of autonomic changes is likely to influence smokers' responses to acute arterial pressure reductions importantly.
Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation.
Authors: Wever E F , Hauer R N , Oomen A , Peters R H , Bakker P F , Robles de Medina E O 
Published: June 2012

BACKGROUND
Prognosis in patients with ventricular tachyarrhythmia without structural heart disease (primary electrical disease) has been described as excellent. However, prognosis may be less favourable in the subgroup surviving an episode of ventricular fibrillation.

METHODS AND RESULTS
We prospectively followed 19 consecutive patients (age, 13 to 66 years; mean age, 33 years) who had survived an episode of documented ventricular fibrillation. Structural heart disease, preexcitation, and long QT syndromes were excluded by thorough cardiologic evaluation. All patients underwent 24-hour Holter monitoring, exercise testing, and programmed electrical stimulation according to a standardized protocol. Holter monitoring revealed episodes of ventricular tachyarrhythmia in 5 patients. Exercise testing reproducibly provoked ventricular tachycardia in 2 patients. Baseline programmed electrical stimulation yielded inducibility of rapid ventricular tachyarrhythmia in 10 patients (53%) and noninducibility in 9 (47%). Nine patients were discharged on antiarrhythmic drug therapy. A defibrillator was implanted in 10 patients. During 43-month follow-up (range, 5 to 85 months; median, 41 months), major arrhythmic events recurred in 7 patients (37%). Four of these patients had noninducibility at baseline programmed electrical stimulation. Two patients on antiarrhythmic drugs had recurrent cardiac arrest: one died suddenly and the other was successfully resuscitated from ventricular fibrillation and subsequently underwent defibrillator implantation. In the other 5 patients, termination of (pre)syncopal episodes was associated with defibrillator shocks. Termination of ventricular fibrillation was documented by Holter recording in one of these patients. Specific markers predictive of a recurrent event could not be identified, although 6 of 7 patients with recurrent events had experienced at least one episode of cardiac arrest or (pre)syncope before the index episode.

CONCLUSIONS
Patients with primary electrical disease presenting with ventricular fibrillation are at high risk of recurrence of major arrhythmic events during long-term follow-up. Noninducibility at baseline study does not predict an uneventful course. Also, early defibrillator implantation should be considered in these patients.
Influence of the status of the renin-angiotensin system on the effect of cilazapril on neointima formation after vascular injury in rats.
Authors: Clozel J P , Müller R K , Roux S , Fischli W , Baumgartner H R 
Published: June 2012

BACKGROUND
Angiotensin converting enzyme (ACE) inhibition has been shown to prevent neointima formation after vascular injury in rats. However, clinical results evaluating restenosis after angioplasty have been negative. The goal of the present study was to evaluate the influence of the renin-angiotensin system (RAS) status on the effect of ACE inhibition on neointima formation.

METHODS AND RESULTS
Arterial injury was produced by ballooning the left carotid artery of rats, and neointima formation was evaluated by morphometry 2 weeks after ballooning. The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA). In parallel groups of rats, measurement of plasma renin activity was made in order to characterize (at least at the plasma level) the status of the RAS. As expected, renal artery stenosis markedly increased plasma renin activity, and DOCA decreased it to undetectable levels. Cilazapril had a marked preventive effect on neointima formation in normotensive rats, spontaneously hypertensive rats, and two-kidney, one-clip rats but was ineffective in DOCA rats.

CONCLUSIONS
We conclude that the status of the RAS has a major influence on the effect of cilazapril on neointima formation after vascular injury.
Activation of human platelets by cocaine.
Authors: Kugelmass A D , Oda A , Monahan K , Cabral C , Ware J A 
Published: June 2012

BACKGROUND
Cocaine ingestion has been associated with thrombosis of coronary as well as peripheral arteries, but the mechanism by which cocaine promotes thrombus formation is unknown. Accordingly, we determined whether cocaine activates human platelets by flow cytometric analysis of whole blood to which cocaine was added.

METHODS AND RESULTS
Activated platelets were detected by "two-color" flow cytometric analysis of the binding of fluorescently labeled antibodies directed against either platelet-associated fibrinogen or P-selectin, which are found on the surface of platelets only after stimulation. Platelets were distinguished from other constituents of whole blood by their ability to bind an anti-glycoprotein Ib antibody bound to both activated and resting platelets. Incubation of whole blood with cocaine, in concentrations of 10 microM to 13 mM, induced significant increases in both platelet-associated fibrinogen (range of increase, 45 +/- 12% to 125 +/- 40%) and P-selectin expression (36 +/- 15% to 112 +/- 24%). In platelets suspended in either buffer or plasma, however, P-selectin expression was detected only at the highest cocaine concentration (85 +/- 13% increase in plasma and 59 +/- 7% in buffer). Neither aspirin nor the ADP scavenger apyrase inhibited cocaine-induced P-selectin expression. Cocaine inhibited the uptake of 14C-radiolabeled serotonin by platelets (IC50, 8.7 microM). P-selectin expression and fibrinogen binding were found after the addition of cocaine alone to blood taken from some but not all donors; however, platelet activation in response to submaximal concentrations of the agonists ADP or epinephrine was enhanced by a low concentration of cocaine added to blood from every donor.

CONCLUSIONS
Cocaine, in concentrations similar to those found clinically, induces activation of individual platelets studied in whole blood from some but not all donors, and platelet response to physiological agonists is enhanced by cocaine. Thus, cocaine-induced platelet activation may contribute to thrombosis following cocaine ingestion.
Erythrocyte ion fluxes in essential hypertensive patients with left ventricular hypertrophy.
Authors: de la Sierra A , Coca A , Paré J C , Sánchez M , Valls V , Urbano-Márquez A 
Published: June 2012

BACKGROUND
Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality in essential hypertension (EH). Several hemodynamic and nonhemodynamic factors have been involved in the development of LVH in hypertension, including abnormalities in cellular ion mobilization.

METHODS AND RESULTS
We measured different ion transport systems in erythrocytes from 50 patients with EH classified as having or not having LVH measured by M-mode echocardiography. Thirty-two EH patients (64%) exhibited criteria of LVH, and 18 (36%) did not. When the two groups were compared, patients with LVH were older (44.7 +/- 7.4 versus 37.6 +/- 9.2 years; P < .01) and exhibited higher rates of erythrocyte Na(+)-H+ exchange (9.8 +/- 4.1 versus 7.1 +/- 2.6 mmol.[L.cells.h]-1; P < .05) and higher intraerythrocyte Na+ content (8.5 +/- 1.3 versus 7.5 +/- 0.8 mmol/L per cell; P < .01). Systolic and diastolic blood pressure values, as well as biochemical, hormonal, and other erythrocyte ion transport systems studied did not differ between EH with or without LVH. The results of a multiple linear regression analysis using left ventricular mass index (LVMI) as the dependent variable showed that Na(+)-H+ exchange and the maximal rate of the Na(+)-K(+)-Cl- cotransport were the only two independently significant parameters associated with an increased LVMI.

CONCLUSIONS
The increased rate of the erythrocyte Na(+)-H+ exchange and the decreased maximal rate of the Na(+)-K(+)-Cl- cotransport system are both associated with the presence of LVH in EH patients. These abnormalities of ion transport pathways tend to increase the intracellular Na+ content and may be involved in the pathogenesis of LVH in EH.
Thallium reinjection demonstrates viable myocardium in regions with reverse redistribution.
Authors: Marin-Neto J A , Dilsizian V , Arrighi J A , Freedman N M , Perrone-Filardi P , Bacharach S L , Bonow R O 
Published: June 2012

BACKGROUND
The clinical significance and pathophysiological mechanisms of reverse redistribution on stress-redistribution thallium-201 myocardial scintigraphy in patients with chronic coronary artery disease are unclear. Recent studies have shown that thallium-201 reinjection is a useful technique for the detection of myocardial viability in chronic coronary artery disease. In this investigation we determined whether thallium reinjection distinguishes viable from nonviable myocardium in regions with reverse redistribution.

METHODS AND RESULTS
We studied 39 patients with chronic stable coronary artery disease (age, 60 +/- 10 years), all of whom demonstrated reverse redistribution on standard exercise-redistribution thallium single-photon emission computed tomography (SPECT). Reverse redistribution was defined as > or = 10% decrease in relative thallium-201 activity between stress and redistribution images and included either the worsening of a perfusion defect apparent on post-stress images or the appearance of a new defect on the redistribution images. Thallium reinjection was performed immediately after the 3- to 4-hour redistribution study. Of 39 regions with reverse redistribution, 32 (82%) showed enhanced thallium-201 activity (> or = 10% increase) after reinjection. In the other 7 regions (18%), the scintigraphic defect persisted after reinjection. Abnormal Q waves were present in only 8 of 32 (25%) regions with enhanced thallium-201 uptake after reinjection compared with 5 of 7 (71%) regions not responding to reinjection (P < .05). Akinetic or dyskinetic wall motion was present in 3 of 32 (9%) regions showing enhanced uptake after reinjection, in contrast with 5 of 7 (71%) regions not responding to reinjection (P < .01). Critically stenosed or totally occluded coronary arteries supplied 24 of 29 (83%) regions with enhanced thallium-201 uptake after reinjection but only 2 of 7 (28%) regions not showing a positive response to reinjection (P < .05). Collateral circulation was detected in 23 of 29 (79%) regions with a positive thallium reinjection effect but in only 1 of the other 7 regions (P < .01). Sixteen of the 39 patients also underwent positron emission tomography using 18F-fluorodeoxyglucose (FDG) to assess glucose utilization and H2(15)O to assess regional blood flow. The 14 regions with reverse redistribution that responded to reinjection with enhanced thallium uptake all showed either normal patterns of FDG uptake and flow or an ischemic pattern with increased FDG uptake relative to flow. Reduced FDG uptake and reduced flow values were seen in the two regions not responding to thallium reinjection.

CONCLUSIONS
These observations indicate that reverse redistribution in chronic coronary artery disease usually reflects viable myocardium, critically dependent upon collateral circulation.
Experimental atrial septal defect closure with a new, transcatheter, self-centering device.
Authors: Das G S , Voss G , Jarvis G , Wyche K , Gunther R , Wilson R F 
Published: June 2012

BACKGROUND
Despite two decades of research, a transcatheter atrial septal defect closure device is not available for clinical use. We have designed a new superelastic Nitinol-Dacron, double-disk, self-centering, atrial septal defect closure device and studied its efficacy in a canine model of atrial septal defects.

METHODS AND RESULTS
Atrial septal defects were created surgically in 20 adult dogs using either a 7.5-mm or 10-mm punch. Percutaneous transcatheter closures were attempted using a new device. The device sizes used were 20 mm in 6 dogs, 22 mm in 9, and 25 mm in 5 (22.1 +/- 1.9 mm, mean +/- SD). The stretched atrial septal defect diameter was 10.5 +/- 1.3 mm, and the device to stretched atrial septal defect diameter ratio was 2.1 +/- 0.3. Closures were successful in 19 studies and unsuccessful in 1. Angiography showed a left-to-right shunt in all 20 dogs before closure. Immediately after closure (n = 19), there were no shunts in 17 and trivial shunts in 2. Six dogs were followed for a period of 4.7 +/- 3.0 months (range, 2 to 8 months). The trivial shunt present in 1 animal immediately after closure had closed by the time of the repeat study. Spontaneous embolization of the device was not seen during follow-up. A solitary wire fracture was found 8 months after closure in 1 device. Light microscopy at 8 weeks in 3 dogs showed the devices to be covered by smooth endocardium, enmeshed in mature collagen tissue, with a minimal mononuclear cell infiltration. Retrievability was assessed by deliberately embolizing 4 devices in 2 dogs into the right atrium (n = 1) and pulmonary artery (n = 3). All devices were successfully retrieved with a snare.

CONCLUSIONS
This feasibility study demonstrates that this new self-centering atrial septal defect closure device has a number of design features that permit effective and safe closures in a canine model. These results support the investigation of this device in human clinical trials.
Effect of inotropic stimulation on the negative force-frequency relationship in the failing human heart.
Authors: Schwinger R H , Böhm M , Müller-Ehmsen J , Uhlmann R , Schmidt U , Stäblein A , Uberfuhr P , Kreuzer E , Reichart B , Eissner H J 
Published: June 2012

BACKGROUND
In severe human heart failure, an increase in frequency of stimulation is accompanied by a reduced force of contraction in vivo and in vitro. The present study was aimed to investigate whether inotropic stimulation influences the inverse force-frequency relationship in failing human myocardium.

METHODS AND RESULTS
The effects of the cAMP-independent positive inotropic agents ouabain (0.01 mumol/L) and BDF 9148 (0.1 mumol/L) as well as the beta-adrenoceptor agonist isoprenaline (0.01 mumol/L and 0.1 mumol/L) on the force-frequency relationship in electrically driven papillary muscle strips from nonfailing (brain death, n = 5) and terminally failing (NYHA class IV, heart transplants, dilated cardiomyopathy, n = 22) human myocardium were studied. For comparison, we examined the effect of elevation of the extracellular Ca2+ concentration (3.2 mmol/L and 6.2 mmol/L). In nonfailing myocardium, force of contraction, peak rate of tension rise, and peak rate of tension decay increased, whereas time to peak tension and time to half relaxation decreased following an increase of stimulation frequency. In NYHA class IV, force of contraction gradually declined followed by changes of other parameters of isometric contraction. Moderate stimulation of contractility by isoprenaline (0.01 mumol/L) partly reversed the negative force-frequency relationship in NYHA class IV and preserved the positive force-frequency relationship in nonfailing myocardium. The addition of ouabain and BDF 9148 together restored completely the force-frequency relationship in NYHA class IV. In contrast, high concentrations of isoprenaline (0.1 mumol/L) and an elevation of the extracellular Ca2+ concentration enhanced the decline in force of contraction in the presence of higher stimulation frequencies.

CONCLUSIONS
It is concluded that functionally important changes occur in the intracellular Ca2+ handling, leading to the negative force-frequency relationship in terminally failing human myocardium. Interestingly, the negative force-frequency relationship can be restored by agents producing positive inotropic effects by elevation of the intracellular Na+ concentration. These findings suggest that hitherto unknown changes in the intracellular ionic homeostasis occur in the failing human heart. Even though increasing [Ca2+]i in failing heart cells may be detrimental, increasing [Na+bdi may be beneficial through a mechanism independent of an increase in [Ca2+]i.
Orthodromic capture of the atrial electrogram during transient entrainment of atrioventricular nodal reentrant tachycardia.
Authors: Satoh M , Miyajima S , Koyama S , Ishiguro J , Okabe M 
Published: June 2012

BACKGROUND
The reentry circuit of atrioventricular nodal reentrant tachycardia (AVNRT) has not been fully demonstrated. We hypothesized that if an upper common pathway was present, the atrial electrogram could not be captured orthodromically during transient entrainment of AVNRT by rapid atrial pacing. Based on this hypothesis, the presence of an upper common pathway was investigated.

METHODS AND RESULTS
The atrial electrogram at the recording site of the His bundle potential was identified during induced AVNRT in 9 patients. To entrain AVNRT transiently, rapid pacing from the high right atrium and coronary sinus was applied at a cycle length 10 milliseconds shorter than that of AVNRT and repeated after a decrement of the paced cycle length in steps of 5 milliseconds until AVNRT was interrupted. In 5 of 7 patients, orthodromic capture of the atrial electrogram at the recording site of the His bundle potential was observed during transient entrainment of AVNRT by coronary sinus pacing, ie, the first postpacing interval of the atrial electrogram at the recording site of the His bundle potential was the same as the paced cycle length. In these 5 patients, the mean minimum paced cycle length capable of orthodromic atrial capture was 349 milliseconds, and the mean difference from the cycle length of AVNRT was only 16 milliseconds. During transient entrainment of AVNRT by high right atrial pacing, the atrial electrogram could not be captured orthodromically.

CONCLUSIONS
Observation of orthodromic capture of the atrial electrogram at the recording site of the His bundle potential by coronary sinus pacing ruled out the presence of an upper common pathway in AVNRT, and the concept that perinodal atrial tissue is involved in the reentry circuit of AVNRT was supported.