bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis.
Authors: Levi M , Biemond B J , van Zonneveld A J , ten Cate J W , Pannekoek H 
Published: June 2012

BACKGROUND
We investigated the effect of inhibition of plasminogen activator inhibitor-1 (PAI-1) activity by a murine monoclonal anti-human PAI-1 antibody (MAI-12) on in vitro thrombolysis and on in vivo thrombolysis and thrombus extension in an experimental animal model for thrombosis.

METHODS AND RESULTS
Thrombolysis, mediated by recombinant tissue-type plasminogen activator (rt-PA), was studied in an in vitro system consisting of fibrinogen, plasminogen, and thrombin. Addition of purified platelets during clot formation inhibited rt-PA-mediated thrombolysis in a dose-dependent manner. Platelet-dependent thrombolysis resistance could be completely neutralized by the monoclonal antibody MAI-12, supporting the notion that the observed resistance is due to PAI-1 released from alpha-granules of platelets. Subsequently, we monitored in vivo thrombolysis and thrombus extension of human whole blood thrombi that were allowed to form in rabbit jugular veins. During thrombus formation, either MAI-12 or an irrelevant antibody was incorporated. Thrombolysis and thrombus extension were simultaneously measured during endogenous thrombolysis or upon administration of different dosages of rt-PA. We observed that endogenous thrombolysis was enhanced in the presence of MAI-12 compared with the control antibody. Significantly, thrombus extension was partially prevented by MAI-12 and not by the control antibody irrespective of whether exogenous rt-PA was systematically administered.

CONCLUSIONS
These observations further confirm the essential role of PAI-1 in the regulation of the thrombolytic system and support the exploration of adjunctive therapy based on inhibition of PAI-1 activity in thrombolytic strategies.
Baroreflex sensitivity and heredity in essential hypertension.
Authors: Parmer R J , Cervenka J H , Stone R A 
Published: June 2012

BACKGROUND
Abnormalities in baroreflex control of heart rate may be important in the pathogenesis of essential hypertension.

METHODS AND RESULTS
To investigate the influence of heredity on baroreflex function, we measured baroreflex sensitivity in 40 untreated patients with essential hypertension grouped by the presence (FH+) or absence (FH-) of a family history of hypertension and in 24 normotensive counterparts. Baroreflex sensitivity was assessed by both high-pressure (phenylephrine bolus) and low-pressure (amyl nitrite inhalation) stimuli. Subject groups were matched for age, blood pressure, body weight, and race. Baroreflex sensitivity (in milliseconds per millimeter of mercury) assessed by amyl nitrite inhalation was 24.3 +/- 2.8 in FH- normotensives, 12.3 +/- 1.7 in FH+ normotensives, 15.4 +/- 3.3 in FH- hypertensives, and 8.1 +/- 1.2 in FH+ hypertensives. Baroreflex sensitivity assessed by phenylephrine bolus was 28.8 +/- 5.6 in FH- normotensives, 19.3 +/- 2.8 in FH+ normotensives, 19.1 +/- 2.0 in FH- hypertensives, and 13.6 +/- 1.3 in FH+ hypertensives. Two-factor analysis of variance showed significant effects on baroreflex sensitivity for blood pressure status (normotensive versus hypertensive) and for family history of hypertension. After control line (controlling) for the effects of several variables, including age, mean arterial pressure, body weight, and race through multiple linear regression analysis, the effect of family history of hypertension on baroreflex sensitivity was still highly significant. Indeed, of all variables investigated, family history of hypertension was the strongest unique baroreflex sensitivity predictor.

CONCLUSIONS
These data suggest that the impairment in baroreflex sensitivity in hypertension is in part genetically determined and may be an important hereditary component in the pathogenesis of essential hypertension.
Electrogram criteria for identification of appropriate target sites for radiofrequency catheter ablation of accessory atrioventricular connections.
Authors: Calkins H , Kim Y N , Schmaltz S , Sousa J , el-Atassi R , Leon A , Kadish A , Langberg J J , Morady F 
Published: June 2012

BACKGROUND
Catheter ablation of accessory atrioventricular (AV) connections using radiofrequency current has been demonstrated to be effective in the majority of patients with the Wolff-Parkinson-White syndrome or paroxysmal supraventricular tachycardia involving a concealed accessory AV connection. However, electrogram criteria have not been established to guide attempts at radiofrequency catheter ablation.

METHODS AND RESULTS
The characteristics of local electrograms recorded at successful and unsuccessful sites of radiofrequency catheter ablation were determined in 132 patients. Electrograms recorded at a total of 438 sites were analyzed: 338 recorded during ablation of 90 manifest accessory AV connections and 100 recorded during ablation of 44 concealed accessory AV connections. During ablation of manifest accessory AV connections, the independent predictors of outcome were electrogram stability (p less than 0.001), the interval between activation of the ventricular electrogram and onset of the QRS complex (p less than 0.001), and the presence of an accessory AV connection potential (p less than 0.001). Radiofrequency energy delivery at sites demonstrating stable electrograms, a probable or possible accessory AV connection potential, and activation of the local ventrical electrogram before the onset of the QRS complex had a 57% probability of success compared with a 3% probability of success at sites without these features. During ablation of concealed accessory AV connections, the independent predictors of outcome were electrogram stability (p = 0.02), the presence of an accessory AV connection potential (p = 0.05), and the presence of retrograde continuous electrical activity (p = 0.04). Sites demonstrating a stable local electrogram, an accessory AV connection potential, and retrograde continuous electrical activity had an 82% probability of success compared with only a 5% probability of success at sites demonstrating none of these features.

CONCLUSIONS
The local electrogram parameters of greatest importance in predicting the success or failure of radiofrequency catheter ablation of accessory AV connections are electrogram stability, the presence of an accessory AV connection potential, and the timing of ventricular activation relative to the QRS complex (for manifest accessory AV connections) or retrograde continuous electrical activity (for concealed accessory AV connections). Awareness of these variables during attempts at radiofrequency catheter ablation of accessory AV connections may minimize the number of unnecessary applications of radiofrequency energy.
Changes in myocardial blood flow during development of and recovery from tachycardia-induced cardiomyopathy.
Authors: Spinale F G , Tanaka R , Crawford F A , Zile M R 
Published: June 2012

BACKGROUND
Chronic supraventricular tachycardia (SVT) causes a dilated cardiomyopathy and myocyte injury. Termination of SVT improves left ventricular (LV) function but is associated with LV hypertrophy. Changes in myocardial blood flow (MBF) that may accompany the development of and recovery from SVT cardiomyopathy might have a significant effect on LV function and myocyte structure. The goal of this study was to relate changes in LV function, myocyte composition, and coronary vascular structure to changes in MBF with the development and recovery of SVT cardiomyopathy.

METHODS AND RESULTS
LV function and MBF were measured in three groups of conscious pigs: sham control (control; n = 8), after 3 weeks of atrial pacing (SVT, 240 beats per minute; n = 8), and after a 4-week recovery from SVT (post-SVT; n = 8) by echocardiography catheterization and microspheres. Measurements were made under three states: 1) at rest with a basal heart rate, 2) rapid atrial pacing (240 beats per minute), and 3) during adenosine infusion (1.5 mumol/l.kg-1.min-1) without pacing. LV myocyte, capillary, and arteriole morphometric studies were performed in five additional pigs from each group using histochemistry and electron microscopy. LV fractional shortening was lower and left atrial pressure was significantly higher in the SVT group compared with control at rest, during pacing, and with adenosine (p less than 0.05). In the post-SVT group, fractional shortening returned to control values at rest and with adenosine, but fell from control values with pacing (p less than 0.05). Left atrial pressure fell in the post-SVT but remained significantly higher than control (p less than 0.05). LV/body weight ratio was significantly increased in the post-SVT group (p less than 0.05). In all states, SVT LVMBF was significantly reduced from control values (rest, 0.8 +/- 0.3 versus 1.6 +/- 0.3 ml-min-1.g-1; pacing, 1.2 +/- 0.2 versus 3.1 +/- 0.3 ml.min-1.g-1; adenosine, 1.4 +/- 0.3 versus 4.4 +/- 0.4 ml.min-1.g-1, respectively, p less than 0.05). In the post-SVT group, LVMBF was similar to control at rest (1.3 +/- 0.2 ml.min-1.g-1) but was significantly lower than control with pacing and adenosine (2.0 +/- 0.4 and 2.5 +/- 0.5 ml.min-1.g-1, respectively, p less than 0.05). Myofibrillar content fell significantly with SVT compared with control (42 +/- 5 versus 61 +/- 3%, p less than 0.05) and returned to control values in the post-SVT group (64 +/- 3%). Capillary density remained unchanged in the SVT and post-SVT groups, but capillary luminal diameter decreased and arteriole diameter increased in the SVT group (p less than 0.05).

CONCLUSIONS
The LV dysfunction and myocyte injury with SVT cardiomyopathy were associated with reduced MBF. Early recovery from SVT cardiomyopathy resulted in hypertrophy with normal MBF at rest, but significantly reduced coronary reserve.
Effect of temperature on digital systolic pressures in lower limb in arterial disease.
Authors: Sawka A M , Carter S A 
Published: June 2012

BACKGROUND
Toe pressures correlate with the chances of healing of skin lesions and with the risk of amputation and mortality. They are not affected by incompressibility of the tibial vessels, which may render ankle pressures inaccurate and reflect the overall arterial obstruction down to the digits. Digital pressures, however, may be affected by temperature.

METHODS AND RESULTS
Measurements under routine laboratory conditions were compared with those at controlled temperatures in 77 limbs with arteriosclerosis obliterans. The desired local temperatures were attained by perfusing water through the cuffs for 7 minutes before the measurements while the flow was interrupted by a tourniquet to allow equilibration of the toe and water temperatures. Mean toe pressure of 34 +/- 4 mm Hg at 10 degrees C was significantly lower (p less than 0.001) than the values during routine measurements (57 +/- 4 mm Hg) and at 30 degrees C (69 +/- 4 mm Hg). The pressure at 30 degrees C was 10 +/- 3 mm Hg higher than during routine measurements when initial digit temperature was below 30 degrees C (p less than 0.01) but not when it was higher. Measurements at 3 degrees C increments from 27 degrees C to 39 degrees C showed progressive increase in pressure (p less than 0.01).

CONCLUSIONS
Pressures at 36 degrees C and 39 degrees C were the highest but were not significantly different from each other. When toe temperature is low under routine conditions, the measured pressure may be falsely low, probably because of an effect on the main digital arteries that leads to delayed opening during deflation of the cuffs. Measurements at warm local temperature will increase the accuracy of the assessment of the severity of the arterial obstruction and may improve prediction of spontaneous healing of skin lesions.
Platelet factor 4 efficiently reverses heparin anticoagulation in the rat without adverse effects of heparin-protamine complexes.
Authors: Cook J J , Niewiarowski S , Yan Z , Schaffer L , Lu W , Stewart G J , Mosser D M , Myers J A , Maione T E 
Published: June 2012

BACKGROUND
It has been observed that the reversal of heparin anticoagulation in humans by protamine sulfate (PS) results in various adverse reactions including leukopenia, thrombocytopenia, activation of complement, increased vascular permeability, systemic hypotension, pulmonary vasoconstriction, and pulmonary edema. The purpose of this study was to compare the efficacy and effects of native platelet factor 4 (PF4) and recombinant platelet factor 4 (rPF4) with those of PS in heparin neutralization in vivo, using a rat model.

METHODS AND RESULTS
Sprague-Dawley rats were anesthetized with sodium pentobarbital, and the right femoral vein and carotid artery were cannulated. For determination of activated partial thromboplastin time, platelet count, white blood cell count, and complement titer, arterial blood samples were taken before and immediately after heparin (10 units/100 g) infusion and at several time points after the infusion of the neutralizing agent (PS, 0.1 mg/100 g; PF4, 0.5 mg/100 g). In separate groups of animals, mean arterial blood pressure was monitored throughout identical protocols and the lungs were prepared for histological examination. The anticoagulant activity of heparin was effectively reversed by all of the neutralizing agents (PS, PF4, and rPF4). Platelet count (48% of initial), white blood cell count (52% of initial), complement titer (60% of initial), and mean arterial pressure (20% decrease) decreased significantly in heparinized animals receiving PS but not in those receiving PF4 or rPF4. Lung interstitium appeared normal when heparin was followed by PF4; however, interstitial edema and hemorrhage were observed with heparin-PS.

CONCLUSIONS
These results suggest that PF4 efficiently reverses heparin anticoagulation in the rat without the adverse effects of heparin-protamine complexes. Therefore, rPF4 may be an appropriate substitute for PS in patients undergoing cardiovascular surgery and other procedures that require heparin anticoagulation.
Improved regional myocardial blood flow, left ventricular unloading, and infarct salvage using an axial-flow, transvalvular left ventricular assist device. A comparison with intra-aortic balloon counterpulsation and reperfusion alone in a canine infarction model.
Authors: Smalling R W , Cassidy D B , Barrett R , Lachterman B , Felli P , Amirian J 
Published: June 2012

BACKGROUND
It has been suggested that left ventricular unloading at the time of reperfusion provides superior infarct salvage over reperfusion alone. The purpose of this study was to show that the Hemopump transvalvular axial-flow left ventricular assist device provides superior left ventricular unloading, ischemic zone collateral blood flow, and infarct size reduction compared with intra-aortic balloon counterpulsation and reperfusion alone.

METHODS AND RESULTS
Eighteen dogs were instrumented with regional myocardial function sonomicrometers in the ischemic and control zones. The left anterior descending coronary artery just distal to the first diagonal branch was instrumented with a silk snare and Doppler flow probe. Additionally, pressure catheters were placed in the left atrial appendage, left ventricular apex, and ascending aorta for hemodynamic measurements. Regional myocardial blood flow was determined by using 15-microns radioactive microspheres. Measurements were made in the control state, immediately after coronary occlusion, at 1 and 2 hours after coronary occlusion, with reperfusion, and 1 hour after reperfusion. In treated animals, left ventricular assistance was maintained during the entire period of occlusion and reperfusion. The Hemopump was associated with a significant decrease in left ventricular systolic and diastolic pressure, whereas mean arterial pressure was maintained. Intra-aortic balloon counterpulsation resulted in no significant changes in left ventricular systolic pressure and a modest decrease in left ventricular diastolic pressure. Regional unloading as assessed by sonomicrometers was significant in the Hemopump animals and absent in the balloon pump animals. Absolute regional myocardial blood flow in the ischemic zone increased slightly (p = 0.002) in the Hemopump animals and did not change in the balloon pump animals. Infarct size expressed as percentage of the zone at risk was 62.6% in the control animals, 27.22% in the balloon pump animals, and 21.7% in the Hemopump animals.

CONCLUSIONS
Mechanical unloading of the ventricle during ischemia and reperfusion appears to result in significant infarct salvage compared with reperfusion alone. The Hemopump appears to provide superior left ventricular systolic and diastolic unloading compared with intra-aortic counterpulsation in a canine model.
Abnormal electrical properties of myocytes from chronically infarcted canine heart. Alterations in Vmax and the transient outward current.
Authors: Lue W M , Boyden P A 
Published: June 2012

BACKGROUND
Reentrant ventricular arrhythmias can occur in the surviving muscle fibers of the epicardial border zone of the canine heart 5 days after coronary artery occlusion. To understand the cellular basis of these arrhythmias, we developed a method of dispersing myocytes (IZs) from the epicardial border zone.

METHODS AND RESULTS
We compared the electrophysiological properties of IZs with those of cells dispersed from the epicardium of control noninfarcted (NZs) and of sham-operated animals (NZsham). Transmembrane action potentials of IZs are reduced in total action potential amplitude and maximum upstroke velocity compared with NZs. However, resting potential of IZs is no different from that of NZs. Action potential duration at -10 mV is significantly reduced in IZs compared with control, and IZ potentials do not show the typical "spike and dome" morphology that is evident in all NZs. Using Vmax as an indirect measure of the peak inward current available for the upstroke of the action potential, we found that the availability curve for IZs is significantly different from the NZ curve. Furthermore, the time course of recovery of Vmax after a depolarizing voltage clamp step was significantly altered in IZs. Using whole-cell voltage clamp techniques, we determined that the voltage-dependent, Ca(2+)-independent, 4-aminopyridine-sensitive transient outward current (ito1) occurred in all NZs (n = 16) but existed in only 37% of IZs (n = 16). There was a significant reduction in the density of ito1 elicited by depolarizing steps in those IZs showing ito1 compared with ito1 density in NZs.

CONCLUSIONS
We have developed a single-cell model of cells that survive in the infarcted heart. Our studies indicate that there are changes in Vmax in IZs. In addition, there is no prominent phase 1 of repolarization in IZ action potentials. This is consistent with the dramatic loss in the function of the ionic channel responsible for the voltage-dependent transient outward current, ito1.
Photodynamic therapy of arteries. A novel approach for treatment of experimental intimal hyperplasia.
Authors: Ortu P , LaMuraglia G M , Roberts W G , Flotte T J , Hasan T 
Published: June 2012

BACKGROUND
Photodynamic therapy (PDT) uses light activation of otherwise nontoxic dyes for the production of reactive oxygen species that cause cell injury and death.

METHODS AND RESULTS
The inhibition of intimal hyperplasia (IH) by PDT was studied in the balloon injury model of the rat carotid artery. Chloroaluminum-sulfonated phthalocyanine (CASPc) was the drug chosen for PDT because it does not produce skin photosensitivity and has a high absorption peak of light at 675 nm, a wavelength with good tissue penetration. A pilot study indicated that CASPc administration with laser radiant exposure of 100 J/cm2 resulted in a homogeneous, circumferential effect on the whole artery. Male Sprague-Dawley rats received the balloon catheter injury to the left common carotid artery (day 0) and were equally divided into two groups. Nine rats received either CASPc (5 mg/kg i.v., n = 6) or saline (n = 3) at day 2, before IH was present, and nine rats received CASPc or saline in the same manner on day 7, when IH was already present. Twenty minutes after drug injection, the distal left common carotid artery was irradiated under saline with 675-nm laser light at 100 mW/cm2 for 10(3) seconds (100 J/cm2). At this low laser irradiance, there are no thermal effects, but photoactivation of CASPc occurs. The rats were killed at day 14 after balloon injury when IH reaches a maximum. The arteries were harvested after perfusion-fixation for light microscopy, histological and computerized morphometric evaluation, and transmission electron microscopy (TEM) analysis. The cross-sectional areas of the neointima were measured in the PDT-treated arteries and in the laser-only control arteries. There was a significant mean +/- SD decrease of IH in the PDT-irradiated segments of the arteries (0.06 +/- 0.05 mm2) versus the laser-only control ones (0.17 +/- 0.07 mm2) (t test, p less than 0.001), with no statistical difference between the day 2 and day 7 treated rats. Lack of IH was correlated in 90% of cases with histological absence of medial smooth muscle cells or inflammatory cells, but no other structural injury was identified. TEM analysis showed early evidence of PDT-mediated cytotoxic effects at 4 hours and the absence of collagen or elastic tissue structural alterations.

CONCLUSIONS
These data demonstrated that PDT can effectively inhibit the IH response when it is used before or during induction of cellular proliferation in this acute model. Although the long-term implications of PDT in arteries need to be defined, this technique may offer a new method for understanding and treating IH.
Smoking is a risk factor for coronary spasm in young women.
Authors: Caralis D G , Deligonul U , Kern M J , Cohen J D 
Published: June 2012

BACKGROUND
Risk factors for pure coronary spasm are not known. Clinical observations have pointed to cigarette smoking, a known risk factor for obstructive coronary artery disease.

METHODS AND RESULTS
We conducted a case-neighborhood control study of premenopausal women, a population segment with the lowest prevalence of obstructive coronary artery disease. The cases were 21 premenopausal women (age range, 36-41 years) with angiographically proven coronary spasm. All coronary arteriograms were analyzed by two independent experienced cardiologists on two occasions. There were no differences between analyses; all cases had normal baseline coronary angiogram except for two, who had less than 20% coronary luminal stenosis in segments other than the site of the focal vasospasm. All cases had normal hemodynamics at rest, normal left ventricular function, and were in sinus rhythm. Ascertainment of the cases was done by angiographic demonstration of focal coronary spasm spontaneously or by ergonovine provocation. Six cases developed spontaneous coronary spasm before catheter engagement, and in 15, coronary spasm was induced by ergonovine provocation. Each case was asked to name as many as possible female neighborhood acquaintances of similar age and racial background who were willing to answer the same standardized questionnaire. The same standardized questionnaire was completed for each case and each control (n = 63). The standardized questionnaire was designed to obtain information on health characteristics, habits, socioeconomic status, and education. Only cigarette smoking was significantly more prevalent among coronary spasm cases. Cigarette smokers were 13 cases (62%) and 11 controls (17.5%) (p less than 0.001). The odds ratio was 7.7, with a 95% confidence interval of 2.6-23.1.

CONCLUSIONS
These findings suggest that there is a very strong association between cigarette smoking and pure coronary spasm in young women.