bluuebunny/crossref_metadata_2025_split huggingface dataset:
Initial contact and subsequent adhesion of human neutrophils or monocytes to human aortic endothelial cells releases an endothelial intracellular calcium store.
Authors: Ziegelstein R C , Corda S , Pili R , Passaniti A , Lefer D , Zweier J L , Fraticelli A , Capogrossi M C 
Published: June 2012

BACKGROUND
Increases in both leukocyte and endothelial cytosolic free [Ca2+] may be involved in intercellular adhesion by regulating the affinity of surface adhesion molecules or by facilitating transendothelial leukocyte migration. The purpose of this study was to examine the effect of initial contact and subsequent adhesion of human neutrophils or monocytes on human aortic endothelial [Ca2+].

METHODS AND RESULTS
Endothelial monolayers were loaded with the fluorescent Ca2+ indicator indo 1 and exposed to isolated human peripheral blood neutrophils or to a cultured human monocyte cell line. A rapid, fourfold to fivefold increase in endothelial cytosolic [Ca2+] occurred within seconds of leukocyte contact. No increase in endothelial [Ca2+] occurred on contact of 18.25-microns inert microspheres, isolated red blood cells, or suspensions of cultured human aortic endothelial cells. In experiments performed on monolayers grown in 1-mm2 capillary flow tubes, the increase in endothelial cytosolic [Ca2+] on initial leukocyte contact was found to be related to the subsequent resistance to leukocyte detachment during exposure to arterial levels of shear stress (13.4 dyne.cm-2). The increase in endothelial cytosolic [Ca2+] during leukocyte contact was not inhibited in Ca(2+)-free buffer but was abolished by prior depletion of an endoplasmic reticulum Ca2+ store by thapsigargin. Pretreatment of neutrophils with R15.7, a specific monoclonal antibody to the adhesion protein CD-18, inhibited the increase in endothelial cytosolic [Ca2+] on neutrophil contact.

CONCLUSIONS
Initial contact leading to subsequent adhesion of human leukocytes to human aortic endothelial cells releases an endothelial intracellular Ca2+ store. This may, in part, be mediated by specific adhesion proteins and may in turn regulate the affinity of surface adhesion molecules or facilitate transendothelial migration of leukocytes.
Local delivery of an antithrombin inhibits platelet-dependent thrombosis.
Authors: Scott N A , Nunes G L , King S B , Harker L A , Hanson S R 
Published: June 2012

BACKGROUND
Platelet-dependent thrombosis can be effectively inhibited by intravenous administration of direct thrombin antagonists. However, an increased propensity for abnormal bleeding has been associated with systemic administration of these agents. The goal of this study was to determine whether local delivery of a potent thrombin inhibitor, D-Phe-L-Pro-L-Arg chloromethyl ketone (PPACK), could inhibit platelet-dependent thrombosis without altering systemic hemostatic function.

METHODS AND RESULTS
Thrombus formation was measured by quantitative imaging of 111In-labeled platelet deposition on segments of thrombogenic vascular graft interposed in arteriovenous shunts in a porcine model. Intravenous administration of PPACK inhibited platelet deposition at a dose of 12.5 micrograms/kg per minute, which was associated with significant prolongations of both template bleeding times and activated partial thromboplastin times. By contrast, local infusion of PPACK at a dose of 0.02 micrograms/kg per minute (ie, a 600-fold smaller dose) into the fluid boundary layer at the interface between flowing blood and the thrombogenic segment produced equivalent inhibition of platelet deposition without prolonging either the bleeding time or the activated partial thromboplastin time. In addition, static exposure of a mural thrombus to solutions of PPACK at concentrations > or = 2.5 mg/mL for 15 minutes produced sustained inhibition of platelet-dependent thrombosis with no change in hemostatic measurements.

CONCLUSIONS
These results indicate that local delivery of the direct antithrombin PPACK, by either boundary layer infusion or static application techniques, effectively inhibits platelet-dependent thrombosis at doses that are several orders of magnitude less than the systemic dose required for an equivalent antithrombotic effect. In contrast to the systemic administration of PPACK, local delivery produced maximal inhibition of thrombosis without alterations in hemostasis.
Characterization of the excitable gap in a functionally determined reentrant circuit. Studies in the sterile pericarditis model of atrial flutter.
Authors: Niwano S , Ortiz J , Abe H , Gonzalez X , Rudy Y , Waldo A L 
Published: June 2012

BACKGROUND
Single premature beats were introduced in the reentrant circuit during stable atrial flutter in the canine sterile pericarditis model to test the hypotheses that (1) despite the fact that the reentrant circuit is functionally determined, there is a fully excitable gap; (2) the excitable gap in the reentrant circuit is not uniform; and (3) inhomogeneities of conduction in the reentrant circuit explain the effects of premature beats.

METHODS AND RESULTS
A multiplexing system was used to record 190 unipolar electrograms from the right atrial free wall during 18 atrial flutter episodes in 9 dogs. In all 18 episodes, premature stimuli captured the atrial flutter reentrant circuit. At the longest coupling intervals, the return cycle at the site closest to the pacing site did not prolong. As the coupling interval of the premature stimulus decreased, the return cycle then progressively increased, associated with changes in conduction in the reentrant circuit that were not uniform. The result was that coupling intervals associated with introduction of the premature beat also were not constant. The mean duration of the total (ie, fully plus partially) excitable gap was 12 +/- 4 ms in areas of slow conduction, and it was always shorter than the total excitable gap in other areas (22 +/- 6 ms, P < .001). The mean duration of the fully excitable gap based on analysis of the return cycle was 4 +/- 1 ms in the reentrant circuit. In 13 of 18 atrial flutter episodes, a premature stimulus terminated atrial flutter by causing block of the orthodromic wave front of the premature beat in an area of slow conduction. The mean coupling interval that caused orthodromic block was 113 +/- 5 ms (recorded at the site just proximal to the area of block), and it was always longer than the delivered stimulus coupling interval at the pacing site (96 +/- 8 ms, P < .001).

CONCLUSIONS
We conclude that in this functionally determined atrial flutter reentrant circuit in the canine sterile pericarditis model, (1) a fully excitable gap is present in at least part of the reentrant circuit; (2) the duration of the excitable gap in the reentrant circuit is shortest in areas of slow conduction; and (3) when a premature beat encounters the partially excitable gap of the reentrant circuit, it results in changes in conduction such that the coupling intervals are not uniform throughout in the reentrant circuit.
Control of rapid ventricular response by radiofrequency catheter modification of the atrioventricular node in patients with medically refractory atrial fibrillation.
Authors: Feld G K , Fleck R P , Fujimura O , Prothro D L , Bahnson T D , Ibarra M 
Published: June 2012

BACKGROUND
Pharmacological control of rapid ventricular response to atrial fibrillation may be difficult in some patients. Alternative treatments, including curative surgery or atrioventricular (AV) node ablation with pacemaker implantation, have significant potential morbidity. In view of evidence that dual AV nodal physiology may exist in a significant percentage of the population, even in those without AV nodal reentrant tachycardia, we postulated that control of ventricular response might be achieved by radiofrequency (RF) catheter ablation in the region of the AV nodal slow pathway with its short refractory period.

METHODS AND RESULTS
Ten patients underwent attempted AV node modification using a 4-mm-tipped electrode catheter positioned in the middle or posterior septum, between the His bundle and coronary sinus ostium on the tricuspid valve annulus. RF energy was applied at 16 to 30 W for up to 60 seconds, until average ventricular response fell below 100 beats per minute. Reduction of maximal ventricular response below 120 beats per minute was confirmed with atropine 1 mg IV. If required, additional ablations were performed progressively more posteriorly up to the coronary sinus ostium. Patients with successful AV node modification were discharged off AV node-blocking drugs and followed in the clinic at regular intervals. Twenty-four-hour ambulatory ECG recordings and/or treadmill stress tests were obtained before and after ablation for statistical comparison of maximum ventricular rate. Resting average ventricular rate was determined during electrophysiology study before and after ablation. In 7 of 10 patients (70%), maximum ventricular rate was reduced from a mean of 164 +/- 12 to 123 +/- 16 beats per minute (P < .01) and average ventricular rate from a mean of 128 +/- 11 to 83 +/- 10 beats per minute after ablation. Mean minimum ventricular rate was 54 +/- 11 beats per minute after ablation. These 7 patients have remained symptom free from rapid ventricular response for a mean of 14 +/- 8 months (range, 1 to 22). Three remain off all AV node-blocking drugs, 3 remain on digoxin alone, which was previously ineffective, and 1 remains on a beta-blocker for angina. In the 3 patients who did not respond to AV node modification, complete AV node ablation and permanent pacemaker implantation was performed in 2 and DC cardioversion after amiodarone loading was performed in 1.

CONCLUSIONS
RF catheter modification of AV node conduction is effective in controlling rapid ventricular response to atrial fibrillation in a significant percentage of medically refractory patients. A possible mechanism of RF modification of AV node conduction is AV nodal slow pathway ablation. Large-scale clinical trials will be needed to determine the overall efficacy and safety of this technique.
Direct in vivo gene transfer into porcine myocardium using replication-deficient adenoviral vectors.
Authors: French B A , Mazur W , Geske R S , Bolli R 
Published: June 2012

BACKGROUND
Efficient methods of introducing genes into myocardial cells must be developed before local somatic cell gene therapy can be implemented against myocardial disease. Although adenoviral (Ad5) vectors have been used to target rodent hearts and plasmid DNA has been directly injected into the myocardium of rats and dogs, the amounts of recombinant protein produced by these procedures have not been reported, and adenoviral vectors have not been used in large mammalian hearts.

METHODS AND RESULTS
Replication-deficient recombinant adenoviral vectors carrying either the luciferase or lacZ reporter genes were injected directly into the ventricular myocardium of adult domestic swine for evaluation of reporter gene expression. This procedure did not affect regional myocardial function as assessed by systolic wall thickening using ultrasonic crystals. Luciferase activity was detected 3 days after injection, increased markedly at 7 days, and then declined progressively at 14 and 21 days. Luciferase production was comparable in the right and left ventricular walls and increased with increasing amounts of virus, reaching 61 +/- 21 ng at the highest dose examined (3.6 x 10(9) plaque-forming units). The injection of 200 micrograms of plasmid DNA (pRSVL) produced levels of luciferase comparable to 1.8 x 10(8) plaque-forming units of recombinant Ad5; however, when normalized to the number of genes injected, the adenovirus was 140,000 times more efficient than plasmid DNA. Histochemical analysis of beta-galactosidase activity produced by a second Ad5 vector demonstrated that nearly all (> 95%) of the stained cells were cardiomyocytes and that the percentage of cardiomyocytes infected by the virus could be quite high in microscopic regions adjacent to the needle track (up to 75% in fields of 60 to 70 cells); however, Ad5-infected cells were rarely observed farther than 5 mm from the injection site. Furthermore, the Ad5 vector induced pronounced leukocytic infiltration that was far in excess of that seen after injection of vehicle alone.

CONCLUSIONS
This study demonstrates for the first time that direct intramyocardial injection of replication-deficient adenovirus can program recombinant gene expression in the cardiomyocytes of a large animal species with relevance to human physiology. The efficiency of adenovirus-mediated gene transfer is far superior to that of plasmid DNA injection, and this method appears to be capable of producing more recombinant protein. However, the cell-mediated immune response to the Ad5 vector and the limited distribution of reporter gene expression suggest that less immunogenic recombinant vectors and more homogeneous administration methods will be required before Ad5 vectors can be successfully used for phenotypic modulation.
Endocarditis risk of the USCI PDA umbrella for transcatheter closure of patent ductus arteriosus.
Authors: Latson L A , McManus B M , Doer C , Kilzer K , Cheatham J P 
Published: June 2012

BACKGROUND
The USCI PDA Umbrella is a device to close patent ductus arteriosus (PDA) by a transcatheter technique. Human clinical trials have shown excellent efficacy in reducing or eliminating the PDA shunt, but concerns remain about the risk of infection with this device. The purpose of this study was to evaluate the risk of infection using an animal model.

METHODS AND RESULTS
Susceptibility to developing endocarditis was tested by injecting a single intravenous dose of group L streptococcus. Ten piglets with a closed ductus served as controls. Two of these developed valvular vegetations. PDA was produced in 19 animals by balloon dilation of the ductus. Seven of 7 animals with PDA at the time of bacterial injection developed endarteritis of the ductus and valvular vegetations. A PDA Umbrella was placed in the remaining 12 animals, and bacteria were injected 2 weeks after device implantation. Infection was evident in the PDA Umbrella only in the single animal in which the Umbrella had embolized and been left in the left pulmonary artery. Three of the remaining 11 piglets had a significant residual leak, and all developed infection in the ductus and an additional valve. Similar to the control group, none of the animals with complete (n = 8) or nearly complete (n = 2) closure of the ductus by the PDA Umbrella had infection in or around the ductus, and only 1 had a valvular vegetation.

CONCLUSIONS
In this animal model, presence of a significant PDA shunt (with or without a PDA Umbrella present) results in significantly increased susceptibility to endarteritis and endocarditis. The PDA Umbrella device does not appear to be susceptible to direct infection as early as 2 weeks after implantation if it is properly located in the ductus arteriosus. Animals with no shunt or a trivial shunt are no more susceptible to developing endocarditis 2 weeks after PDA Umbrella implantation than are controls.
Cardiovascular effects of inhaled nitric oxide in patients with left ventricular dysfunction.
Authors: Loh E , Stamler J S , Hare J M , Loscalzo J , Colucci W S 
Published: June 2012

BACKGROUND
Pulmonary vascular resistance (PVR) is frequently elevated in patients with advanced heart failure. Nitric oxide (NO), which contributes to the activity of endothelium-derived relaxing factor, causes relaxation of pulmonary arteries and veins in vitro. Inhalation of NO gas causes pulmonary vasodilation in patients with primary and secondary forms of pulmonary hypertension.

METHODS AND RESULTS
To test the hypothesis that inhalation of NO gas lowers PVR in patients with heart failure, we studied the hemodynamic effects of a 10-minute inhalation of NO (80 ppm) in 19 patients with New York Heart Association class III (n = 5) and class IV (n = 14) heart failure due to left ventricular (LV) dysfunction. Although inhalation of NO had no effect on pulmonary artery pressures, the PVR decreased by 31 +/- 7% (P < .001) due to a 23 +/- 7% increase (P < .001) in pulmonary artery wedge pressure and despite a 4 +/- 2% (P < .05) decrease in cardiac index. The magnitude of the decrease in PVR with inhaled NO was inversely related (r = -.713; P < .001) to the baseline PVR. Inhaled NO had no effect on heart rate, systemic arterial pressure, systemic vascular resistance, or LV peak +dP/dt or -dP/dt.

CONCLUSIONS
In patients with heart failure due to LV dysfunction, inhalation of NO causes a decrease in the PVR associated with an increase in LV filling pressure. These findings predict that inhaled NO, if used alone at this dose (80 ppm), may have adverse effects in patients with LV failure.
Abnormal diurnal variation of blood pressure, cardiac output, and vascular resistance in cardiac transplant recipients.
Authors: Idema R N , van den Meiracker A H , Balk A H , Bos E , Schalekamp M A , Man in 't Veld A J 
Published: June 2012

BACKGROUND
An attenuated or absent nocturnal decline in blood pressure has repeatedly been documented in cardiac transplant recipients. The present study was aimed at investigating the hemodynamic mechanism underlying this abnormality.

METHODS AND RESULTS
In 23 cardiac transplant recipients (11 to 36 months after transplantation) and in 23 control subjects matched for age and 24-hour mean arterial pressure, invasive 24-hour ambulatory blood pressure was measured by means of the Oxford technique. Beat-to-beat relative values of stroke volume were determined by means of a pulse-contour method, and relative changes of cardiac output (stroke volume x heart rate) and total peripheral vascular resistance (blood pressure/cardiac output) over the 24-hour period were calculated. The nocturnal decline in blood pressure was 20 +/- 8% (mean +/- SD) in control subjects but only 5 +/- 9% (P < .001) in cardiac transplant recipients. In control subjects, the nocturnal decline in blood pressure was associated with a nocturnal fall in cardiac output of 24 +/- 13%, whereas vascular resistance compared with daytime value did not change. The small nocturnal decline in blood pressure in cardiac transplant recipients was associated with an attenuated nocturnal fall in cardiac output of 14 +/- 12% (P < .05 versus control subjects). In addition, vascular resistance compared with daytime value was increased by 9 +/- 9% (P < .05) during the night. Both in cardiac transplant recipients and in control subjects, the nocturnal changes in blood pressure were correlated with the nocturnal changes in cardiac output but not with the nocturnal changes in total peripheral vascular resistance.

CONCLUSIONS
This study confirms the attenuated nocturnal fall in blood pressure in cardiac transplant recipients. Hemodynamically, this attenuated blood pressure decline is characterized by a reduced nocturnal fall in cardiac output, and it is associated with a nocturnal increase in vascular resistance.
Role of nitric oxide in exercise-induced vasodilation of the forearm.
Authors: Endo T , Imaizumi T , Tagawa T , Shiramoto M , Ando S , Takeshita A 
Published: June 2012

BACKGROUND
We wished to determine the role of NO in exercise-induced metabolic forearm vasodilation.

METHODS AND RESULTS
Young healthy volunteers (n = 11) underwent static handgrip exercise (4 to 5 kg, 3 minutes). Forearm blood flow (FBF) measured by strain plethysmography increased from 4.1 +/- 0.7 mL.min-1.100 mL-1 at rest to 9.8 +/- 1.2 mL.min-1.100 mL-1 immediately after exercise and gradually decreased thereafter. Exercise was repeated after intrabrachial artery infusion of NG-monomethyl-L-arginine (L-NMMA) at 4.0 mumol/min for 5 minutes. L-NMMA did not alter blood pressure and heart rate. L-NMMA decreased FBF at rest to 2.9 +/- 0.4 mL.min-1.100 mL-1 (P < .01), peak FBF immediately after exercise to 7.2 +/- 0.7 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation (P < .01). Calculated oxygen consumption during peak exercise was comparable before and after L-NMMA. Intra-arterially infused L-arginine (10 mg/min, 5 minutes) reversed the inhibitory effect of L-NMMA. To determine the effect of the decrease in resting FBF on exercise-induced hyperemia, we normalized FBF after exercise by resting FBF. The percent increases in FBF after exercise from resting FBF were similar before and after L-NMMA. Furthermore, we examined the effect of intra-arterially infused angiotensin II on FBF at rest and after exercise (n = 7). Angiotensin II decreased FBF at rest from 3.1 +/- 0.3 to 1.8 +/- 0.3 mL.min-1.100 mL-1 (P < .01), peak FBF after exercise from 8.1 +/- 0.5 to 5.6 +/- 0.5 mL.min-1.100 mL-1 (P < .01), and FBF during the mid to late phase of metabolic vasodilation. The effects of L-NMMA and angiotensin II on FBF at rest and exercise were similar.

CONCLUSIONS
Our results suggest that L-NMMA decreased FBF after exercise largely by decreasing resting FBF. These results suggest that NO may not play a significant role in exercise-induced metabolic arteriolar vasodilation in the forearm of healthy humans.
Magnetic resonance and echocardiographic imaging of pulmonary artery size throughout stages of Fontan reconstruction.
Authors: Fogel M A , Donofrio M T , Ramaciotti C , Hubbard A M , Weinberg P M 
Published: June 2012

BACKGROUND
Because pulmonary artery size is considered by most investigators to be a major prognosticator of outcome in patients undergoing staged Fontan reconstruction, the objective of the present study was to determine the efficacy of noninvasive measures in determining pulmonary artery size.

METHODS AND RESULTS
This study analyzed the T1-weighted, spin-echo magnetic resonance and echocardiographic images of 36 functional single-ventricle patients throughout stages of Fontan reconstruction (prebidirectional and postbidirectional cavopulmonary anastomosis and after Fontan) and compared them with angiography images at cardiac catheterization. Magnetic resonance imaging had a high degree of agreement with angiography, with the McGoon index agreeing better than the Nakata index and absolute right and left pulmonary diameters. Although echocardiography had fair agreement with angiography, it agreed less well and had a wider standard deviation than magnetic resonance imaging for all indexes and measurements and, based on the prediction interval, would be a poorer prospective measure of pulmonary artery size in this population. In addition, echocardiography was a poorer measure of pulmonary artery size as the size of the vessel increases. Magnetic resonance imaging correctly detected five of five patients with nonconfluent branch pulmonary arteries and six of six patients with stenoses, whereas echocardiography was unable to visualize any of the patients with nonconfluent branch pulmonary arteries with certainty and only two of six (33%) with stenoses.

CONCLUSIONS
Magnetic resonance imaging is a useful, noninvasive tool to determine pulmonary artery size in patients undergoing Fontan reconstruction and is superior to echocardiography. Echocardiography was a fair predictor of pulmonary artery size, but magnetic resonance imaging agreed with angiography better than echocardiography and outperformed echocardiography in diagnosing branch pulmonary artery discontinuity and stenoses. Magnetic resonance imaging may avoid unnecessary cardiac catheterization, especially in older patients, and may obviate the need for jugular or subclavian catheterization in those who have undergone bidirectional cavopulmonary anastomosis.