bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunohistochemical localization of basic and acidic fibroblast growth factors in the developing rat heart.
Authors: Spirito P , Fu Y M , Yu Z X , Epstein S E , Casscells W 
Published: June 2012

BACKGROUND
We used biochemical and immunohistochemical techniques to investigate the expression and distribution of immunoreactive basic and acidic fibroblast growth factors (bFGF and aFGF, respectively) in the hearts of rat embryos (11-20 days of gestation) and of postnatal rats (1-35 days after birth). Our purpose was to assess the relation between the cellular distribution of these growth factors and histogenetic and morphogenetic events in the developing heart.

METHODS AND RESULTS
Western-blot analysis of heparin-bound material from neonatal heart extracts identified a single band with a molecular weight of approximately 18 kD for both bFGF and aFGF. Five antibodies for bFGF and three for aFGF showed superimposable distribution of immunoreactive bFGF and aFGF in the heart at each stage examined. At the cellular level, these peptides were localized in the cytoplasm and extracellular matrix. In the myocytes, immunostaining was positive throughout the embryonic and neonatal periods. In the majority of the mesenchymal cells of the cushions and endothelial cells of endocardium and vessels, staining was also positive. In the smooth muscle cells of the aorta, other large arteries, and coronary arteries, immunostaining was intensely positive at early stages of development but became faint or negative with increasing cell differentiation.

CONCLUSIONS
The wide distribution of immunoreactive bFGF and aFGF that we identified in the developing rat heart suggests that these growth factors play an important role in heart cytodifferentiation and morphogenesis. Their superimposable distribution may reflect functional interaction. The progressive changes in their distribution suggest a changing role for these peptides during organogenesis.
Protection against infarction afforded by preconditioning is mediated by A1 adenosine receptors in rabbit heart.
Authors: Liu G S , Thornton J , Van Winkle D M , Stanley A W , Olsson R A , Downey J M 
Published: June 2012

BACKGROUND
Preconditioning (5 minutes of ischemia followed by 10 minutes of recovery) renders the heart very resistant to infarction from subsequent ischemia. This study tests whether adenosine receptors might mediate preconditioning protection.

METHODS AND RESULTS
We examined the effect on infarct size of pretreatment with either of two adenosine receptor antagonists in both control and preconditioned in situ rabbit hearts. Hearts underwent 30 minutes of regional ischemia plus 3 hours of reperfusion, and infarct size was measured with tetrazolium. Infarct size averaged 39% of the zone at risk in controls but only 8% in preconditioned hearts. Preconditioned and nonpreconditioned hearts receiving either blocker had infarcts not different in size from the controls. A 5-minute intracoronary infusion of adenosine was as effective as 5 minutes of ischemia in protecting parabiotically perfused isolated hearts against infarction from a 45-minute ischemic insult. Similarly, intracoronary infusion of N6-1-(phenyl-2R-isopropyl)adenosine, an A1-selective adenosine receptor agonist, at a dose that delayed conduction but did not dilate the coronary vessels, also limited infarct size. The protection disappeared when we reduced the coronary concentration of drug by intravenous infusion of adenosine, indicating that cardiac rather than peripheral receptors were involved in the protection.

CONCLUSIONS
We conclude that adenosine released during the preconditioning occlusion stimulates cardiac A1 receptors, which leaves the heart protected against infarction even after the adenosine has been withdrawn.
Neutrophil accumulation in ischemic canine myocardium. Insights into time course, distribution, and mechanism of localization during early reperfusion.
Authors: Dreyer W J , Michael L H , West M S , Smith C W , Rothlein R , Rossen R D , Anderson D C , Entman M L 
Published: June 2012

BACKGROUND
We have previously demonstrated that chemotactic factors released from the ischemic canine myocardium peak early during reperfusion and that they elicit neutrophil adherence reactions in vitro that are dependent on the CD18 glycoprotein family. In this study we investigated the hypothesis that neutrophil localization in ischemic canine myocardium in vivo occurs over a similar time course during early reperfusion and involves a CD18-dependent mechanism.

METHODS AND RESULTS
We occluded the circumflex coronary artery for 1 hour in acute, open-chest dogs, followed by reperfusion for 1, 2, 3, or 4 hours. Regional myocardial blood flow was determined using radiolabeled microspheres, and localization was traced using technetium-99m-labeled autologous neutrophils. In the first hour of reperfusion, neutrophil localization occurred preferentially within the subendocardial region and was inversely related to flow. Neutrophil localization diminished across the ischemic myocardium from endocardium to epicardium but remained negatively related to flow in the midmyocardial region. Regardless of flow, little neutrophil localization occurred in the subepicardial region. Neutrophil localization was greatest in the first hour of reperfusion and diminished thereafter. By 4 hours of reperfusion, the rate of localization was markedly attenuated relative to 1 hour. Dogs given anti-CD18 monoclonal antibody R15.7 (1 mg/kg i.v.) before occlusion underwent 1 hour of occlusion followed by 1 hour of reperfusion. When compared with 1-hour reperfusion controls, the R15.7-treated dogs demonstrated significant attenuation of neutrophil localization in the subendocardial region.

CONCLUSIONS
These data support the concepts that rapid neutrophil localization during reperfusion occurs within regions of previous myocardial ischemia and that neutrophils preferentially localize within the subendocardial region. The rate of neutrophil localization is greatest within the first hour after the initiation of reperfusion, and localization is, at least in part, CD18 dependent. Therapies directed against neutrophil-mediated reperfusion injury should be initiated with these considerations in mind.
Circumferential myocardial shortening in the normal human left ventricle. Assessment by magnetic resonance imaging using spatial modulation of magnetization.
Authors: Clark N R , Reichek N , Bergey P , Hoffman E A , Brownson D , Palmon L , Axel L 
Published: June 2012

BACKGROUND
Conventional cardiac imaging methods do not depict true segmental myocardial shortening, since they cannot determine segment length between fixed points in the myocardium.

METHODS AND RESULTS
We used electrocardiographically gated magnetic resonance imaging with spatial modulation of magnetization to noninvasively "tag" the myocardium with dark stripes at uniform 7-mm intervals center to center at end diastole. We then determined end-systolic stripe separation and thereby calculated circumferential shortening. When end systole was not reached in the first image series, a second temporally overlapped series starting in late systole was used to determine late-systolic shortening. Septal, anterior, lateral, and inferior segments were assessed at endocardium, midwall, and epicardium on five midventricular short-axis sections each in 10 normal volunteers. A transmural gradient in circumferential shortening was observed, with the percentage of endocardial segment shortening consistently greater than epicardial segment shortening (epicardial, 22 +/- 5%; midwall, 30 +/- 6%; and endocardial, 44 +/- 6%; p less than 0.0001 by analysis of variance). Circumferential shortening varied from apex to base with slices closer to the base of the left ventricle showing less shortening at the midwall (28 +/- 9%) and endocardium (39 +/- 6%) than more apical slices at the midwall (34 +/- 13%) and endocardium (49 +/- 9%) (p less than 0.05 and p less than 0.01, respectively, by analysis of variance).

CONCLUSIONS
Transmural and longitudinal heterogeneity of circumferential shortening is present in the normal human left ventricle. Magnetic resonance imaging with spatial modulation of magnetization is a powerful new tool for assessment of circumferential shortening and provides information unobtainable with conventional imaging methods.
Radiofrequency catheter ablation of the atrioventricular junction from the left ventricle.
Authors: Sousa J , el-Atassi R , Rosenheck S , Calkins H , Langberg J , Morady F 
Published: June 2012

BACKGROUND
The purpose of this study was to describe a new technique for catheter ablation of the atrioventricular junction using radiofrequency energy delivered in the left ventricle.

METHODS AND RESULTS
Catheter ablation of the atrioventricular (AV) junction using a catheter positioned across the tricuspid annulus was unsuccessful in eight patients with a mean +/- SD age of 51 +/- 19 years who had AV nodal reentry tachycardia (three patients), orthodromic tachycardia using a concealed midseptal accessory pathway, atrial tachycardia, atrial flutter (two patients), or atrial fibrillation. Before attempts at catheter ablation of the AV junction, each patient had been refractory to pharmacological therapy, and four had failed attempts at either catheter modification of the AV node using radiofrequency energy or surgical and catheter ablation of the accessory pathway. Conventional right-sided catheter ablation of the AV junction using radiofrequency energy in six patients and both radiofrequency energy and direct current shocks in two patients was ineffective. The mean amplitude of the His bundle potential recorded at the tricuspid annulus at the sites of unsuccessful AV junction ablation was 0.1 +/- 0.08 mV, with a maximum His amplitude of 0.03-0.28 mV. A 7F deflectable-tip quadripolar electrode catheter with a 4-mm distal electrode was positioned against the upper left ventricular septum using a retrograde aortic approach from the femoral artery. Third-degree AV block was induced in each of the eight patients with 20-36 W applied for 15-30 seconds. The His bundle potential at the sites of successful AV junction ablation ranged from 0.06 to 0.99 mV, with a mean of 0.27 +/- 0.32 mV. There was no rise in the creatine kinase-MB fraction and no complications occurred. An intrinsic escape rhythm of 30-60 beats/min was present in seven of the eight patients. Each patient received a permanent pacemaker and has been asymptomatic during 3-13 months of follow-up.

CONCLUSIONS
Catheter ablation of the AV junction can be achieved effectively and safely using radiofrequency energy delivered in the left ventricle when the conventional right-sided approach is unsuccessful.
Percutaneous excimer laser coronary angioplasty of lesions not ideal for balloon angioplasty.
Authors: Cook S L , Eigler N L , Shefer A , Goldenberg T , Forrester J S , Litvack F 
Published: June 2012

BACKGROUND
Excimer laser coronary angioplasty is a new, investigational technique for treating coronary artery stenoses. Initial reports have demonstrated acute efficacy and relative safety of this procedure, but have not addressed the effect of lesion type on acute success and complication rates.

METHODS AND RESULTS
In the first 100 patients undergoing percutaneous excimer laser coronary angioplasty at our institution, acute laser success was obtained in 84% and procedural success was obtained in 94%. There were six acute closures during laser angioplasty and one myocardial infarction. Two patients required emergency coronary bypass surgery. Sixty-five percent of patients had lesions not ideal for balloon angioplasty because of lesion morphology (tubular, diffuse, or chronic total occlusion) or ostial location. There were 10 tubular stenoses, 29 diffuse lesions, 18 chronic total occlusions, and eight ostial lesions, including five aorto-ostial lesions. In this nonideal subgroup, the acute success rate with laser was 86% (72% of chronic total occlusions and 91% of non-totally occluded lesions), and the procedural success rate was 94%. There were three acute occlusions during laser angioplasty but no myocardial infarctions, emergency bypass surgeries, or deaths. One coronary artery perforation occurred without clinical sequelae. Laser angioplasty was successful in four of six lesions (67%) in which balloon angioplasty had failed. Laser success was obtained in 10 of 11 (91%) moderately or heavily calcified stenoses. Eight eccentric lesions and two lesions on bends were successfully treated without dissection or perforation. No side branch occlusions occurred in the 15 patients in whom one or more major branches originated within the lesion treated. Adjunctive balloon angioplasty was performed in 47% of cases, usually to obtain a larger final luminal diameter. Need for adjunctive balloon angioplasty decreased to 36% after a larger (2.0 mm) laser catheter became available. Twenty-eight percent of the 105 lesions treated were American College of Cardiology/American Heart Association classification type A, 47% were type B, and 25% were type C. Laser and procedural successes were obtained in 83% and 97% of type A, 88% and 96% of type B, and 85% and 88% of type C lesions, respectively.

CONCLUSIONS
In our initial experience, excimer laser angioplasty was found to be acutely effective and safe therapy for lesions identified as not ideal for balloon angioplasty. This technique may provide a useful adjunct or alternative to balloon angioplasty in selected patients.
Effects of aging, gender, and physical training on peripheral vascular function.
Authors: Martin W H , Ogawa T , Kohrt W M , Malley M T , Korte E , Kieffer P S , Schechtman K B 
Published: June 2012

BACKGROUND
Blood pressure and total peripheral resistance increase with age. However, the effect of age on vasodilatory capacity has not been characterized.

METHODS AND RESULTS
To delineate the effects of aging, gender, and physical training on peripheral vascular function, we measured blood pressure during submaximal and maximal treadmill exercise and measured blood pressure, calf blood flow, and calf conductance (blood flow/mean blood pressure) at rest and during maximal hyperemia in 58 healthy sedentary subjects (men aged 25 +/- 5 and 65 +/- 3 years and women aged 27 +/- 5 and 65 +/- 4 years) and in 52 endurance exercise-trained subjects (men aged 30 +/- 3 and 65 +/- 4 years and women aged 27 +/- 3 and 65 +/- 3 years). Systolic and mean blood pressures were higher at rest, during maximal calf hyperemia, and during submaximal exercise of the same intensity in the older than in the younger subjects of the same gender and exercise training status (p less than 0.01). The magnitude of the age-related effect on blood pressure during exercise was greater in women than in men (p less than 0.01). Diastolic blood pressure during submaximal exercise was also higher in the older than in the younger subjects (p less than 0.05) but not in women treated with estrogen replacement. In contrast, systolic and mean blood pressures during submaximal work were lower in physically conditioned subjects than in sedentary age- and gender-matched subjects (p less than 0.05) but not in older women. Increased age was associated with reduced maximal calf conductance in women (p less than 0.01) but not in men. However, calf vasodilatory capacity was higher in trained than in untrained subjects (p less than 0.01), regardless of age and gender. There was a significant inverse relation between maximal calf conductance and systolic, diastolic, and mean blood pressures during submaximal exercise (r = -0.31 to -0.53, p less than 0.01) and a direct relation between maximal calf conductance and maximal oxygen uptake (r = 0.66, p less than 0.0001).

CONCLUSIONS
Thus, for healthy subjects between the ages of 25 and 65 years, there is an interactive effect between age and gender and an independent effect of physical training on peripheral vascular function.
Hypercholesterolemia enhances macrophage recruitment and dysfunction of regenerated endothelium after balloon injury of the rabbit iliac artery.
Authors: Weidinger F F , McLenachan J M , Cybulsky M I , Fallon J T , Hollenberg N K , Cooke J P , Ganz P 
Published: June 2012

BACKGROUND
We studied the effects on and possible interaction of balloon denudation and hypercholesterolemia on large arteries in the rabbit with special regard to structure and vascular reactivity.

METHODS AND RESULTS
New Zealand White rabbits fed a 1% cholesterol diet or a standard diet for 14 weeks underwent balloon denudation of the left iliac artery 4 weeks before death. Both the balloon-injured and the control iliac arteries were harvested for in vitro studies of vascular reactivity, for immunohistochemical staining with monoclonal antibodies directed at smooth muscle cells and macrophages, and for scanning electron microscopy. Balloon injury caused intimal smooth muscle proliferation with little macrophage infiltration and was followed by recovery of endothelium-dependent vasodilator function within 4 weeks. Hypercholesterolemia caused macrophage-rich lesions confined to the intima with moderate impairment of endothelial vasodilator function. Balloon injury in the setting of hypercholesterolemia caused intimal smooth muscle cell proliferation and intense macrophage infiltration throughout the arterial wall and severe impairment of endothelial vasodilator function. Scanning electron microscopy confirmed regrowth of the endothelium in all balloon-injured vessels. In the balloon-injured arteries of hypercholesterolemic animals, the regenerated endothelium exhibited areas of atypical morphology not seen after balloon injury or hypercholesterolemia alone.

CONCLUSIONS
The present study shows that balloon injury, hypercholesterolemia, and their combination cause distinct lesions and functional disturbances. An arterial balloon injury in the setting of hypercholesterolemia produces a diffuse inflammatory response that is accompanied by a sustained impairment of endothelial function and a marked proliferative response.
Prevention of arterial reocclusion after thrombolysis with recombinant lipoprotein-associated coagulation inhibitor.
Authors: Haskel E J , Torr S R , Day K C , Palmier M O , Wun T C , Sobel B E , Abendschein D R 
Published: June 2012

BACKGROUND
This study was designed to determine whether arterial reocclusion after thrombolysis can be prevented by lipoprotein-associated coagulation inhibitor (LACI), a physiological inhibitor of tissue factor-induced coagulation mediated by the extrinsic pathway.

METHODS AND RESULTS
Thrombosis was induced in femoral arteries of anesthetized dogs with the use of anodal current to elicit extensive vascular injury and formation of platelet-rich thrombi in one artery and with thrombogenic copper wire to elicit fibrin-rich thrombi without appreciable vascular injury in the contralateral artery. Recanalization of both vessels was induced with t-PA (1.7 mg/kg i.v. over 1 hour) and verified with Doppler flow probes. Reocclusion occurred within 2 hours in seven of seven arteries with electrical injury-induced thrombosis and in four of seven arteries with copper wire-induced thrombosis in the absence of LACI. In dogs given infusions of recombinant DNA-produced LACI (225 micrograms/kg over 15 minutes, followed by 4 micrograms/kg/min i.v.) after completion of the infusion of t-PA, no reocclusion occurred during the 2-hour interval of observation in any of the five arteries subjected to electrical injury (p less than 0.001), and cyclic partial occlusions were nearly abolished (0.4 +/- 0.4/hr in LACI-treated dogs compared with 13.7 +/- 5.5/hr in saline-treated dogs, p less than 0.0001). In contrast, reocclusion occurred in two of five arteries with indwelling copper wires, and cyclic partial occlusions were unaffected despite LACI. LACI prolonged the partial thromboplastin time modestly (1.7 +/- 0.2 x baseline) but did not affect platelet counts or aggregation assessed ex vivo.

CONCLUSIONS
Inhibition of the extrinsic pathway of coagulation with LACI prevents thrombotic arterial reocclusion after thrombolysis in vessels subjected to extensive vascular injury. Our results demonstrate that activation of the extrinsic pathway plays a critical role in thrombotic reocclusion and that LACI provides a highly targeted approach to facilitate sustained recanalization without directly inhibiting platelets.
Cerebral vasoconstriction during head-upright tilt-induced vasovagal syncope. A paradoxic and unexpected response.
Authors: Grubb B P , Gerard G , Roush K , Temesy-Armos P , Montford P , Elliott L , Hahn H , Brewster P 
Published: June 2012

BACKGROUND
To determine the effect of vasovagally mediated syncope on the cerebral circulation, transcranial Doppler sonography was used to assess changes in cerebral blood flow velocity during head-upright tilt-induced syncope.

METHODS AND RESULTS
Thirty patients (17 men and 13 women; mean age, 43 +/- 22 years) with recurrent unexplained syncope were evaluated by use of an upright tilt-table test for 30 minutes, with or without an infusion of intravenous isoproterenol (1-4 micrograms/min), in an attempt to provoke bradycardia, hypotension, or both. Transcranial Doppler sonography was used to assess middle cerebral artery systolic velocity (Vs), diastolic velocity (Vd), ratio of systolic to diastolic velocities, pulsatility index (PI = Vs-Vd/Vmean), and resistance index (RI = Vs-Vd/Vs) before, during, and after tilt. Syncope occurred in six patients (20%) during the baseline tilt and 14 (46%) during isoproterenol infusion (total positives, 66%). In the tilt-positive patients, concomitant with the development of hypotension and bradycardia, transcranial Doppler sonography showed a 75 +/- 17% decrease in diastolic velocity, unchanged systolic velocity, a 46 +/- 17% decrease in mean velocity, a 295 +/- 227% increase in pulsatility index, and a 73 +/- 34% increase in resistance index.

CONCLUSIONS
These findings reflect increased cerebrovascular resistance secondary to arteriolar vasoconstriction distal to the insonation point of the middle cerebral artery. This is paradoxic because the expected response of the cerebral circulation to hypotension is vasodilation. We conclude that abnormal baroreceptor responses triggered during vasovagal syncope result in a derangement of cerebral autoregulation with paradoxic vasoconstriction in the face of increasing hypotension.