bluuebunny/crossref_metadata_2025_split huggingface dataset:
Roles of thrombin and platelet membrane glycoprotein IIb/IIIa in platelet-subendothelial deposition after angioplasty in an ex vivo whole artery model.
Authors: Kaplan A V , Leung L L , Leung W H , Grant G W , McDougall I R , Fischell T A 
Published: June 2012

BACKGROUND
Platelet deposition at the site of injury caused by balloon angioplasty is associated with acute closure and restenosis.

METHODS AND RESULTS
In a new ex vivo whole artery angioplasty model, we examined the roles of thrombin inhibition with D-Phe-Pro-ArgCH2Cl (PPACK) and inhibition of the platelet membrane fibrinogen receptor glycoprotein IIb/IIIa (GPIIb/IIIa) with monoclonal antibody 7E3 on platelet deposition at the site of balloon injury. Fresh rabbit aortas were mounted in a perfusion chamber. One half of the mounted arterial segment was dilated with a standard angioplasty balloon catheter and the uninjured half served as the control segment. The vessels were perfused with human blood at physiological pressure and shear rates of 180-250 second-1 for 30 minutes. Platelet deposition was measured using 111In-labeled platelets and scanning electron microscopy. With heparin (2 units/ml) anticoagulation, 8.2 +/- 2.2 x 10(6) platelets/cm2 were deposited at the site of balloon injury compared with 0.7 +/- 0.2 x 10(6) platelets/cm2 on uninjured segments (p less than 0.02, n = 7). PPACK was tested at a concentration (10 microM) that totally inhibited platelet aggregation in response to thrombin. 7E3 was tested at a concentration (10 micrograms/ml) that totally inhibited platelet aggregation. Platelet deposition at the site of balloon injury was reduced 47% by PPACK and 70% by 7E3 compared with heparin.

CONCLUSIONS
At shear rates seen in nonstenotic coronary arteries, PPACK and 7E3 are more effective than heparin in reducing platelet deposition at the site of balloon injury. The significant inhibition of platelet deposition by PPACK demonstrates the importance of heparin-resistant thrombin in platelet thrombus formation. The 7E3 results suggest that approximately 70% of platelet deposition at the site of balloon injury is GPIIb/IIIa dependent and that the remaining 30% results from non-GPIIb/IIIa-mediated platelet-subendothelial adhesion. Finally, the ex vivo whole artery system is a useful model for studying platelet-vessel wall interactions under physiologically defined parameters.
Relation of early hemodynamic changes to final cardiac phenotype and survival after neural crest ablation in chick embryos.
Authors: Tomita H , Connuck D M , Leatherbury L , Kirby M L 
Published: June 2012

BACKGROUND
Microcinephotography was used to study a model of persistent truncus arteriosus created in chick embryos by ablation of premigratory neural crest destined for the third and fourth aortic arch arteries as well as the septum of the cardiac outflow tract.

METHODS AND RESULTS
Twenty-five control embryos and 105 of 202 experimental embryos were filmed on day 3 of incubation and then reincubated. The remaining 97 experimental embryos were not filmed because of twisting of the embryos, but they were reincubated. There was no difference in either the survival rate (p greater than 0.23) from day 3 to day 11 of incubation or the incidence of persistent truncus arteriosus (p greater than 0.08) between the filmed and the nonfilmed embryos. Incomplete looping of the cardiac tube observed in experimental embryos during early cardiogenesis correlated with a right ventricular origin of the outflow vessels in the definitive heart. Hemodynamic measurements indicated that there was no difference in heart rate, ejection fraction, systolic and diastolic areas, stroke volume, and cardiac output between controls and the experimental group as a whole. However, embryos that did not survive to day 11 had decreased stroke volume (p less than 0.001) and cardiac output (p less than 0.001), whereas embryos that survived to day 11 with cardiac malformations had increased stroke volume and cardiac output in early embryogenesis.

CONCLUSIONS
Increased stroke volume and cardiac output may be necessary factors for survival in embryos with cardiac dysmorphogenesis and probably are associated with dilation of the ventricular portion of the cardiac tube, which leads to malalignment of the outflow vessel or vessels.
A new method for quantitation of mitral regurgitation based on color flow Doppler imaging of flow convergence proximal to regurgitant orifice.
Authors: Bargiggia G S , Tronconi L , Sahn D J , Recusani F , Raisaro A , De Servi S , Valdes-Cruz L M , Montemartini C 
Published: June 2012

BACKGROUND
Imaging of the flow convergence region (FCR) proximal to a regurgitant orifice has been shown to provide a method for quantifying the regurgitant flow rate. According to the continuity principle, the FCR is constituted by concentric hemispheric isovelocity surfaces centered at the orifice. The flow rate is constant across all isovelocity surfaces and equals the flow rate through the orifice. For any isovelocity surface the flow rate (Q) is given by: Q = 2 pi r2 Vr, where 2 pi r2 is the area of the hemisphere and Vr is the velocity at the radial distance (r) from the orifice.

METHODS AND RESULTS
We studied 52 consecutive patients with mitral regurgitation (mean age, 49 years; age range, 21-66 years) verified by left ventricular angiography using color flow mapping. The FCR r was measured as the distance between the first aliasing limit--at a Nyquist limit obtained by zero-shifting the velocity cutoff to 38 cm/sec--and the regurgitant orifice. Seven patients without evidence of an FCR had only grade 1+ mitral regurgitation angiographically. There was a significant relation between the Doppler-derived maximal instantaneous regurgitant flow rate and the angiographic degree of mitral regurgitation in the other patients (rs = 0.91, p less than 0.001). The regurgitant flow rate by Doppler also correlated with the angiographic regurgitant volume (r = 0.93, SEE = 123 ml/sec) in the 15 patients in normal sinus rhythm and without other regurgitant lesions in whom it could be measured. The correlation between regurgitant jet area within the left atrium and the angiographic grade was only fair (rs = 0.75, p less than 0.001).

CONCLUSIONS
Color flow Doppler provides new velocity information about the proximal FCR in patients with mitral regurgitation. According to the continuity principle, the maximal instantaneous regurgitant flow rate, obtained with the FCR method, may provide a quantitative estimate of the severity of mitral regurgitation, which is relatively independent of technical factors.
Ultrasonic energy. Effects on vascular function and integrity.
Authors: Fischell T A , Abbas M A , Grant G W , Siegel R J 
Published: June 2012

BACKGROUND
Ultrasonic energy transmitted via flexible wire probes provides a new means of ablating atherosclerotic plaque. We studied the effects of ultrasonic energy (20 kHz) delivered via a ball-tipped wire probe on arterial vasomotor behavior in rabbit thoracic aortas in a perfused whole-vessel model.

METHODS AND RESULTS
After precontraction with phenylephrine (10(-5) M) or KCl (60 mM), the effects of ultrasonic energy (0.7-5.5 W x 60 seconds, 42-330 J) on arterial vasomotor behavior were measured using long-axis ultrasonic vessel imaging of the proximal (ultrasonic probe-treated) and distal (untreated) control segments. The efficacy of plaque ablation at these same probe-tip power outputs was evaluated in atherosclerotic, human cadaver iliofemoral arteries. Ultrasonic energy caused dose (energy)-dependent relaxation in rabbit aortas after precontraction with phenylephrine in arteries with endothelium (n = 8) and without endothelium (n = 8) (p less than 0.001 versus ultrasound treated at power outputs of 2.9 and 5.5 W). There was no difference in the relaxation dose responses between endothelialized and endothelially denuded segments (p = NS). Ultrasonic energy also caused significant relaxation (67 +/- 8%) after voltage-dependent precontraction with 60 mM KCl. Temperature measurements revealed less than 1 degrees C warming of the vessel wall during as long as 2 minutes of treatment at a power output of 5.5 W. Pathological examination showed no smooth muscle injury at (moderate) power outputs that caused arterial relaxation. At probe-tip power outputs of 2.9-5.5 W, ultrasonic energy recanalized two of two totally occluded cadaveric iliofemoral vessel segments. The ultrasonic ablation catheter was also demonstrated to cause arterial relaxation in a recanalized canine femoral artery in vivo.

CONCLUSIONS
Ultrasonic energy delivered via a flexible-wire probe produces dose-dependent, endothelium-independent smooth muscle relaxation capable of reversing both receptor-mediated and voltage-dependent vasoconstriction in vitro. At moderate power outputs, this relaxation response does not appear to be due to thermal effects or irreversible smooth muscle cell injury. This vasorelaxant effect of ultrasonic energy is also apparent in vivo, at doses that effectively ablate atherosclerotic plaque, and may improve the safety of arterial recanalization using ultrasonic energy.
Proarrhythmic effects of flecainide. Experimental evidence for increased susceptibility to reentrant arrhythmias.
Authors: Brugada J , Boersma L , Kirchhof C , Allessie M 
Published: June 2012

BACKGROUND
The goal of this study was to investigate the nature and electrophysiological mechanisms of the proarrhythmic effects of flecainide in Langendorff-perfused rabbit hearts.

METHODS AND RESULTS
A thin layer of epicardium was obtained by an endocardial cryotechnique in 10 Langendorff-perfused rabbit hearts. Six other hearts were kept intact. Programmed electrical stimulation using up to three closely coupled premature stimuli and burst pacing was used to test the inducibility of arrhythmias both during control and administration of 1 micrograms/ml flecainide. During control, in the thin layer of epicardium, application of one to three premature stimuli induced nonsustained ventricular tachycardia in out of 10 hearts, and burst pacing induced nonsustained ventricular tachycardia in four hearts and sustained ventricular tachycardia in two hearts. During administration of 1 microgram/ml flecainide, application of one to three premature stimuli induced sustained ventricular tachycardia in five hearts, and burst pacing induced sustained ventricular tachycardia in nine hearts. All tachycardias were based on circus movement of the impulse around arcs of functional block. During administration of flecainide, different locations of the arc of block could be found in the same heart, leading to different reentrant circuits with different cycle lengths. In the control group of six intact hearts, application of up to three closely coupled premature stimuli in all cases induced ventricular fibrillation both during control and administration of flecainide.

CONCLUSIONS
Flecainide alters propagation of the impulse in thin surviving layers of myocardium in a manner that facilitates the induction of functionally determined reentry.
Psychological factors related to prehospital delay during acute myocardial infarction.
Authors: Kenyon L W , Ketterer M W , Gheorghiade M , Goldstein S 
Published: June 2012

BACKGROUND
Prior studies have had difficulty identifying factors that significantly explain patients' delay in responding to symptoms of acute myocardial infarction (AMI).

METHODS AND RESULTS
We therefore examined factors affecting the time between symptom onset and hospital arrival for 103 AMI patients admitted to a Detroit metropolitan hospital between October 1989 and January 1990. Variables evaluated included demographic and medical history factors, psychological characteristics of somatic and emotional awareness, and type A behavior. The mean prehospital delay time was 9.0 +/- 10.8 hours (median, 5.0 hours; range, 0.25-62.0 hours). Delay time was not significantly associated with demographic or medical history categories or with type A behavior. Of study variables that can be identified prior to evolution of an AMI, somatic and emotional awareness were the only factors significantly predictive of delay time. Patients who were more capable of identifying inner experiences of emotions and/or bodily sensations sought treatment significantly earlier than patients with low emotional or somatic awareness (low emotional awareness median delay, 12.8 hours; high emotional awareness median delay, 3.8 hours; low somatic awareness median delay, 7 hours; high somatic awareness median delay, 4 hours).

CONCLUSIONS
Variations in sensitivity to bodily sensations and emotions appear to play an important role in treatment seeking and thus potentially in treatment outcome for AMI patients. Assessment of these characteristics in patients with coronary risk factors could allow early identification of persons at risk of excessive delay in responding to symptoms of AMI.
Responses of atherosclerotic human coronary arteries in vivo to the endothelium-dependent vasodilator substance P.
Authors: Crossman D C , Larkin S W , Dashwood M R , Davies G J , Yacoub M , Maseri A 
Published: June 2012

BACKGROUND
The effects of the endothelium-dependent vasodilator substance P (SP) on atherosclerotic human coronary arteries was studied.

METHODS AND RESULTS
[125I]-SP binding to luminal cells was shown to be preserved in the atherosclerotic epicardial coronary arteries of four patients. No binding to medial smooth muscle cells was demonstrated. Intracoronary infusions of SP were undertaken in patients with coronary artery disease. SP was infused for 2-minute periods starting at a dose of 2.8 pmol/min rising by doubling increments to 22.4 pmol/min. Analysis of the epicardial coronary artery diameter, using a computerized analysis system (CAAS) of the angiograms, was performed at the end of each infusion. Analysis of seven smooth vessel segments from seven coronary vessels, which were stenosed at more proximal sites, was performed. Significant dose-dependent dilatation was seen (p = 0.04), which was maximal at 5.6 pmol/min SP. No additional dilatation was produced with 2 mg intracoronary isosorbide dinitrate (ISDN). Two of these seven patients showed no response to SP, and only one of these appeared to sustain dilatation with ISDN (2 mg intracoronary). In a second group of six patients with discrete coronary stenoses, analysis at the site of the stenosed segments appeared to reveal dilatation in response to SP in only one instance. One other stenotic segment dilated with isosorbide dinitrate but failed to dilate with SP; the remaining four were fixed. The segment immediately proximal to the stenosis preserved a dose-dependent vasodilator response.

CONCLUSIONS
These findings demonstrate that the endothelium-dependent vasodilator substance P can still produce epicardial vasodilatation in vivo in the presence of coronary atherosclerosis.
Growth of the great vessels in the normal human fetus and in the fetus with cardiac defects.
Authors: Ursell P C , Byrne J M , Fears T R , Strobino B A , Gersony W M 
Published: June 2012

BACKGROUND
There is a paucity of quantitative anatomic data regarding human great vessel development that could be useful as a reference for fetal echocardiographers who must distinguish abnormal from normal cardiac development at early stages.

METHODS AND RESULTS
To determine normal growth patterns, we plotted the diameters of the aortic and pulmonary valves, ductus arteriosus, aortic isthmus, and descending aorta in 274 autopsy specimens from nonselected spontaneous abortuses of normal karyotype. There was a linear increase in the diameters of these structures within the developmental period studied (10-26 weeks). A relative narrowing of the aorta at the isthmus compared with the aortic valve and descending aorta probably indicates that the majority of fetal left heart output goes to the developing heart and brain. In contrast to previous studies of late gestation and neonatal animals, however, we found that the diameter of the aortic isthmus was larger than that of the ductus arteriosus, suggesting substantial isthmic blood flow in these midtrimester fetuses. Among nineteen other hearts with diverse defects, both of two hearts with a narrow isthmus had an enlarged ductus arteriosus and one heart with pulmonary atresia/intact septum had a narrow ductus and increased aortic valve diameter.

CONCLUSIONS
During midgestation, the normal heart may have substantial aortic isthmic blood flow that diminishes due to rerouting in late gestation when increased requirements of the fetal brain and other organs prevail. Although fetal shunts may explain some vessel abnormalities, the majority of cardiac defects in this study were not associated with abnormal growth of the great vessels within this developmental age range.
Radiation exposure during radiofrequency catheter ablation of accessory atrioventricular connections.
Authors: Calkins H , Niklason L , Sousa J , el-Atassi R , Langberg J , Morady F 
Published: June 2012

BACKGROUND
Catheter ablation of accessory atrioventricular (AV) connections has been demonstrated to be effective in more than 85% of patients. One of the risks of this procedure is radiation exposure during the fluoroscopic imaging necessary to guide catheter manipulation. The objective of the present study was to measure the radiation received by patients and physicians during radiofrequency catheter ablation and to estimate the resultant somatic and genetic risks.

METHODS AND RESULTS
Radiation exposure to patients and physicians was measured during attempts at radiofrequency catheter ablation of accessory AV connections in 31 consecutive patients. Radiation exposure was measured using thermoluminescent sensors placed on the patient and on the physician. Somatic and genetic risks were estimated based on the radiation levels recorded using these sensors. The durations of fluoroscopy and of the catheter ablation procedure were recorded for each patient. Catheter ablation was successful in 28 of 31 patients (90%). Mean +/- SD duration of fluoroscopy was 44 +/- 40 minutes. The largest patient radiation dose was measured over the ninth vertebral body posteriorly (median, 7.26 rem [roentgen equivalents man]; range, 0.31-135.7 rem). Median radiation dose to the thyroid was 0.46 rem (range, 0.06-7.26 rem), and median radiation dose to the posterior iliac crest was 2.43 rem (range, 0.01-8.3 rem). The greatest radiation dose to the operator was recorded at the left hand (99 mrem). Mean radiation dose to the operator's eyes was 28 mrem.

CONCLUSIONS
Radiofrequency catheter ablation of accessory AV connections may result in significant radiation exposure to the patient and to the physician. Each hour of fluoroscopic imaging is associated with a lifetime risk of developing a fatal malignancy of 0.1% and a risk of a genetic defect of 20 per 1 million births. Although these risks must be recognized, they are relatively small compared with the risks associated with alternate approaches to management, including no therapy, antiarrhythmic drug therapy, and surgery.
Antithrombotic effects of combining activated protein C and urokinase in nonhuman primates.
Authors: Gruber A , Harker L A , Hanson S R , Kelly A B , Griffin J H 
Published: June 2012

BACKGROUND
We have determined in vivo the relative antithrombotic efficacy and hemostatic safety of combining low-dose activated protein C (APC) and urokinase (urinary plasminogen activator, u-PA), two natural proteins that regulate thrombogenesis.

METHODS AND RESULTS
To model acute thrombotic responses of native blood under conditions of arterial flow, thrombogenic segments of Dacron vascular graft (VG) were incorporated into chronic exteriorized femoral arteriovenous (AV) access shunts in baboons. Thrombus formation on VG was determined by measuring 1) the deposition of autologous 111In platelets using real-time scintillation camera imaging, 2) the accumulation of 125I fibrin, 3) segment patency by Doppler flow analysis, and 4) blood tests for thrombosis, including plasma concentrations of platelet factor 4, beta-thromboglobulin, fibrinopeptide A (FPA), and D-dimer. Treatments consisting of low-dose and intermediate-dose APC (0.07 or 0.25 mg/kg.hr), u-PA (25,000 or 50,000 IU/kg.hr), or the combination were administered for 1 hour by continuous intravenous infusion. In untreated controls, platelets and fibrin accumulated rapidly, reaching plateau values at 1 hour of 15.1 +/- 3.8 x 10(9) platelets and 7.8 +/- 2.2 mg fibrin. Although the low-dose APC or u-PA alone did not decrease either platelet or fibrin deposition significantly, this combination moderately reduced both platelet and fibrin accumulation (7.3 +/- 2.6 x 10(9) platelets, p less than 0.05; 3.9 +/- 0.6 mg fibrin, p less than 0.05). Furthermore, intermediate-dose APC or u-PA reduced thrombus formation by half when administered alone (p less than 0.001 for both platelet and fibrin deposition), and the combination markedly interrupted the accumulation of platelets (3.0 +/- 1.0 x 10(9) platelets, p less than 0.001) and fibrin (1.3 +/- 0.6 mg fibrin, p less than 0.001). During active treatments, all VG segments remained patent. Hemostatic plug forming capability, as measured by template bleeding times, remained normal during all experiments (p greater than 0.05). The T50 clearance time for APC activity was not affected by the concurrent administration of u-PA. u-PA alone increased the plasma levels of D-dimer, FPA, and, interestingly, APC, implying that during pharmacological activation of the fibrinolytic system, thrombin activity was released, and the protein C pathway was activated.

CONCLUSIONS
A combination of intermediate-dose APC and u-PA produce substantial and efficient antithrombotic effects without impairing hemostatic function.