bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vascular injury and time course of smooth muscle cell proliferation after experimental holmium laser angioplasty.
Authors: Hassenstein S , Hanke H , Kamenz J , Oberhoff M , Hanke S , Riessen R , Haase K K , Betz E , Karsch K R 
Published: June 2012

BACKGROUND
In vitro experiments have shown that holmium laser energy can effectively ablate even calcified plaque in human arterial vessels. Because high-energy densities from holmium lasers can easily be transmitted through quartz fibers, this solid-state laser has been suggested as an alternative intraluminal treatment of atherosclerotic plaque.

METHODS AND RESULTS
To develop an intimal plaque, 35 New Zealand White rabbits underwent electrical stimulation of their right carotid artery for 28 days. Subsequently, in 25 rabbits, holmium laser angioplasty (wavelength, 2.12 microns; pulse duration, 150 microseconds; energy density, 350 mJ/mm2) was performed. To study the morphological results, the vessels were excised after 7, 14, 28, and 42 days. Cross sections were analyzed in regard to laser-specific injury. Staining of alpha-actin was used to identify smooth muscle cells (SMCs). After bromodeoxyuridine labeling, the extent of proliferation (number of cells undergoing DNA synthesis) was determined by using a monoclonal antibody. Holmium laser ablation resulted in an initial decrease of the numbers of intimal cell layers in the early group (7 days after treatment: 5 +/- 1 cell layers with 76 +/- 39 microns; control: 13 +/- 3 cell layers with 144 +/- 44 microns). Quantification of SMCs undergoing DNA synthesis in the intima (control: 51 +/- 19 cells/mm2) showed a significant increase of labeled cells after 7 (216 +/- 74 cells/mm2, p = 0.003) and 14 days (281 +/- 139 cells/mm2, p = 0.011). Integrity of the internal elastic lamina was disrupted in all animals after intervention. Seven and 14 days after treatment, a considerable reduction of medial cell nuclei was found in 10 of 12 animals. SMC proliferation in the medial layer was increased within the first 2 weeks after laser ablation (168 +/- 113 cells/mm2; control: 8 +/- 4 cells/mm2; p = 0.023). Six weeks after holmium laser angioplasty, SMC proliferation had returned to control levels in the intima and remained increased in the medial layer. This proliferative response resulted in a significant increase of intimal thickening within 6 weeks after laser ablation (30 +/- 6 cell layers, 375 +/- 97 microns resp.; p = 0.001 each).

CONCLUSIONS
Holmium laser treatment leads to considerable vessel wall injury and results in SMC proliferation in the intimal and medial layer with a maximum of proliferative activity within the first 2 weeks. Subsequently, this results in considerable intimal and medial hyperplasia within 6 weeks after treatment.
Preoperative prediction of the outcome of coronary revascularization using positron emission tomography.
Authors: de Silva R , Yamamoto Y , Rhodes C G , Iida H , Nihoyannopoulos P , Davies G J , Lammertsma A A , Jones T , Maseri A 
Published: June 2012

BACKGROUND
Previous assessments of myocardial viability using positron emission tomography (PET) relied on demonstration of glucose metabolism in hypoperfused asynergic segments using the glucose analogue [18F]2-fluoro-2-deoxyglucose (FDG). Recently, it was shown that myocardial viability could be assessed by calculating the water-perfusable tissue index (PTI) for the asynergic region. PTI represents the proportion of the myocardium that is capable of rapid transsarcolemmal exchange of water and thus perfusable by water. The aim of the present study was to assess myocardial viability by PET using PTI in patients undergoing coronary revascularization.

METHODS AND RESULTS
Twelve patients with chronic coronary artery disease and previous myocardial infarction were studied. Analysis of transmission (tissue density) and 15O-labeled carbon monoxide (blood pool), and 15O-labeled water (myocardial blood flow [MBF]) emission PET data enabled the simultaneous quantification of MBF (ml.min-1.g perfusable tissue-1) and PTI (gram of perfusable tissue per gram of total anatomic tissue). In addition, PET imaging with FDG after 75-g oral glucose load was performed in eight patients. Preoperative echocardiography identified 33 hypocontractile and 26 control segments. Follow-up echocardiography performed 3 to 5 months later demonstrated 26 of 33 segments with improved wall motion (recovery) and seven of 33 segments without improvement (nonrecovery). MBF in the control segments (0.97 +/- 0.22 ml.min-1.g perfusable tissue-1) was significantly higher (p < 0.001) than in both the recovery (0.73 +/- 0.18 ml.min-1.g perfusable tissue-1) and the nonrecovery (0.45 +/- 0.11 ml.min-1.g perfusable tissue-1) segments. PTI in the recovery regions (0.99 +/- 0.15) was > or = 0.7 in all cases and slightly less than in control regions (1.10 +/- 0.15, p < 0.02). FDG uptake in these regions was 92 +/- 17% (n = 13) of the uptake in control segments with normal wall motion. In the nonrecovery group, PTI was 0.62 +/- 0.06 (p < 0.02 versus control and recovery) and always < 0.7. In the one patient in whom a comparison with metabolic imaging was made, FDG uptake was 46% of the uptake in a reference region with normal wall motion.

CONCLUSIONS
These data showed that contractile recovery occurred only in segments where PTI was > or = 0.7, suggesting that > or = 70% of myocardial tissue in a given asynergic segment should be perfusable by water to enable contractile recovery. There was good agreement between the PTI and FDG methods for predicting improvements in regional wall motion after revascularization. Although further studies should be performed in a larger patient group, the preliminary results are promising and suggest that PTI may be a good predictor of contractile recovery after coronary revascularization.
Natural history and patterns of recovery of contractile function in single left ventricle after Fontan operation.
Authors: Sluysmans T , Sanders S P , van der Velde M , Matitiau A , Parness I A , Spevak P J , Mayer J E , Colan S D 
Published: June 2012

BACKGROUND
Before the era of the Fontan procedure, the typical course of patients with single left ventricle (LV) consisted of heart failure and death during the second or third decade of life. Despite the advent of effective palliative therapy, ventricular dysfunction remains a significant clinical problem for these patients.

METHODS AND RESULTS
To investigate the causes of ventricular dysfunction in these patients and to determine whether Fontan-type repair reverses deterioration of LV function, the ventricular dimensions, volume, shape, wall stress, and systolic function were determined by echocardiography in 84 patients 0.2-35 years old with double-inlet single LV or tricuspid atresia. Measurements were obtained in 67 patients after palliation (arterial shunt or pulmonary artery band) and in 47 patients a median of 4.4 years after a Glenn (n = 9) or a Fontan operation (n = 38). Before a Fontan procedure, ventricular volumes were 2 to 3 times normal. Ventricular afterload, assessed as circumferential and meridional end-systolic wall stress, became abnormal after 2 years of age. With age, LV shape changed progressively from ellipsoidal to spherical, as indicated by the decrease in long axis:short axis ratio from normal (1.9) toward unity. Concomitantly, the ratio of circumferential to meridional end-systolic wall stress fell from 1.3 to unity, the ratio of a sphere at equilibrium. This age-related change in shape and load occurred in concert with progressive deterioration of LV systolic function and contractility. Aortic oxygen saturation, an indicator of pulmonary blood flow and therefore volume work in single-ventricle physiology, was inversely and independently correlated with contractility. In the group of patients in whom a Glenn or a Fontan operation was performed at < 10 years of age, ventricular dimensions, volumes, and wall stress diminished and LV function and contractility improved after surgery (p < 0.001). In patients undergoing surgery after 10 years of age, few had improvement of LV function after surgery. Postoperative ventricular function and contractility were inversely related to age at surgery and to aortic oxygen saturation measured before surgery.

CONCLUSIONS
Although Fontan-type repair of single ventricle early in life is associated with reversal of the abnormal contractile mechanics associated with age and volume load, this capacity for recovery diminishes with age at surgery.
Augmented forearm vasoconstriction during dynamic exercise in healthy older men.
Authors: Taylor J A , Hand G A , Johnson D G , Seals D R 
Published: June 2012

BACKGROUND
We tested the hypothesis that the nonactive limb vasoconstriction evoked during large-muscle dynamic exercise becomes augmented with aging in humans.

METHODS AND RESULTS
Sixteen young control subjects (age, 26 +/- 1 year) and twelve older (65 +/- 1 year) healthy men with similar chronic physical activity levels were studied during supine leg cycling exercise. Both peak work load (1,100 +/- 60 versus 1,400 +/- 40 kpm/min) and peak O2 uptake (1.85 +/- 0.10 versus 2.38 +/- 0.07 l/min) were lower in the older men (p < 0.05). There were no differences in the two groups under conditions of quiet supine (basal) rest. During cycling for 5 minutes each at mild, moderate, and heavy submaximal intensities (approximately 45%, 65%, and 85% of peak O2 uptake), the increases in arterial blood pressure generally were similar in the young and older subjects; however, heart rate rose less in the older men (p < 0.05). Whole forearm blood flow (venous occlusion plethysmography) was lower and vascular resistance was higher (approximately 55-90%) in the older men at all loads (p < 0.05), but the steady-state forearm skin blood flow responses (laser Doppler velocimetry) were not different in the two groups. The increases in antecubital venous norepinephrine concentrations were greater in the older men at each work load (p < 0.05), although the plasma epinephrine responses were similar in the two groups. In other studies, 1) peak whole forearm reactive hyperemia and vascular conductance after sustained circulatory arrest (ischemia) were slightly (approximately 20%) but not significantly lower in the older men and 2) the forearm vasoconstrictor and plasma norepinephrine responses to a nonexercise sympathoexcitatory stimulus (limb immersion in ice water) tended to be blunted in the older men.

CONCLUSIONS
During brief, submaximal, large-muscle dynamic exercise, healthy older men demonstrate augmented forearm vasoconstriction that is probably caused by greater constriction of skeletal muscle resistance vessels; this appears to be mediated, at least in part, by increased sympathetic outflow. These altered sympathetic vasoconstrictor adjustments do not represent a nonspecific hyperresponsiveness to acute stress with human aging. Finally, the regulation of arterial blood pressure appears to be normal in these healthy older men.
Diastolic vibration improves systolic function in cases of incomplete relaxation.
Authors: Takagi T , Koiwa Y , Kikuchi J , Honda H , Hoshi N , Butler J P , Takishima T 
Published: June 2012

BACKGROUND
Incomplete relaxation of the left ventricle (LV) affects LV filling, but the subsequent effect on LV systolic function remains unclear. We attempted to improve relaxation by applying oscillatory mechanical perturbation during diastole (diastolic vibration) and examined the extent to which systolic function improved.

METHODS AND RESULTS
Using 10 open-chest canine preparations, pacing tachycardia and administration of propranolol were imposed to induce various levels of incomplete relaxation. Myocardial length perturbation was induced with an oscillator attached to the LV surface (50 Hz, 1-mm amplitude) and was restricted to the period from the beginning of isovolumic relaxation to end diastole. At resting heart rates, diastolic vibration caused an immediate decrease in the time constant (T) of LV pressure fall without any influence on heart rate, LV peak systolic pressure (peak LVP), stroke volume (SV), LV peak positive dP/dt, and total systemic vascular resistance. With pacing tachycardia, diastolic vibration increased both peak LVP and SV at 160 beats per minute (before) and 120 beats per minute (after propranolol), simultaneously decreasing both T and LV diastolic pressures and increasing end-diastolic segment length. The increase in peak LVP and SV caused by diastolic vibration correlated with the T/diastolic interval (r = 0.82), the assumed index of severity of incomplete relaxation.

CONCLUSIONS
These results suggest that diastolic vibration accelerates the LV relaxation rate and that this increased relaxation improves systolic function through the Frank-Starling mechanism.
Effects of calcium channel blockers on calcium uptake in rat aortic valve allografts.
Authors: Thompson S A , Smith G B , Cobb S M , Walters K S , Behrendt D M 
Published: June 2012

BACKGROUND
The life span of human aortic valve allografts is finite, and many fail because of cusp rupture or calcification. Subcellular changes occurring in aortic valves in response to transplantation include the uptake of calcium. This study uses a heterotropic rat aortic valve transplant model to determine whether the calcium channel blockers diltiazem and verapamil might attenuate leaflet calcification.

METHODS AND RESULTS
The 60 rats studied were divided into the following groups: 1) control: valves from normal, unoperated F1 generation of Lewis and Brown Norway cross (LBNF1) rats; 2) control: valves from syngeneic transplant combinations (Lewis/Lewis); 3) control: valves from allogeneic transplant combinations (LBNF1/Lewis, donor/recipient); 4) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day diltiazem; 5) experimental: valves from allogeneic strain combinations treated with 30 mg/kg per day verapamil. Drugs or saline (controls) were administered with osmotic pumps placed subcutaneously 2 days before transplantation. Animals were killed 3 weeks later, and the valves were harvested and prepared for calcium analysis. Energy-dispersive x-ray microanalysis was used to measure the calcium in a section of one leaflet from each valve studied. Paired t tests showed that allograft valves treated with diltiazem or verapamil contained significantly less calcium than allograft controls treated with saline (p < 0.001). When all five groups were subjected to one-way ANOVA, the valves in the allograft control group contained significantly more calcium than all other groups. All other groups were not different from each other.

CONCLUSIONS
The calcium channel blockers verapamil and diltiazem were effective in preventing early calcification that occurs in aortic valves after transplantation. Thus, these agents might play a role in prolonging the life of human aortic valve allografts.
Induction of endothelial cell expression of the plasminogen activator inhibitor type 1 gene by thrombosis in vivo.
Authors: Fujii S , Sawa H , Saffitz J E , Lucore C L , Sobel B E 
Published: June 2012

BACKGROUND
We have shown previously that products from activated platelets can augment synthesis of plasminogen activator inhibitor type 1 (PAI-1) in cultured endothelial and hepatoma (Hep G2) cells in vitro and increase plasma PAI-1 activity in vivo in rabbits. Accordingly, the effects of activation of platelets associated with thrombosis and thrombolysis in vivo on plasma PAI-1 activity and expression of the PAI-1 gene in endothelium, liver, and other organs were characterized.

METHODS AND RESULTS
Endothelial injury giving rise to platelet-rich thrombi was induced with electrical stimulation in carotid arteries in rabbits. Clot lysis and recanalization were induced subsequently with intravenous tissue-type plasminogen activator (t-PA) and verified with Doppler flow probes. Plasma PAI-1 activity (mean +/- SD) increased from 6 +/- 2 arbitrary units (AU)/ml to 129 +/- 48 AU/ml (n = 15) within several hours after recanalization. When t-PA had failed to induce recanalization, the increase was much less (from 7 +/- 2 to 42 +/- 23 AU/ml, n = 11). To define mechanisms responsible for these changes, PAI-1 messenger RNA (mRNA) was evaluated by Northern blot analysis and localized in tissues by in situ hybridization. Strong and consistent induction of PAI-1 mRNA was evident in aorta, heart, and liver of animals subjected to thrombosis (twofold to threefold increases compared with values in controls), particularly in those in which thrombolysis had been induced (fourfold to sixfold). After thrombolysis, an intense, PAI-1 mRNA-specific signal was detected in endothelium of aorta, liver, and heart, with less intense signals in endothelium of lung, adrenals, and kidneys.

CONCLUSIONS
The increases in plasma PAI-1 activity follow a preceding increase in endothelial cell expression of the PAI-1 gene as reflected by PAI-1 mRNA levels. Thus, increased synthesis of endothelial cell PAI-1 after thrombosis and thrombolysis may attenuate endogenous fibrinolysis early after coronary thrombolysis, thereby potentiating early, thrombotic reocclusion.
Adenosine-sensitive ventricular tachycardia. Clinical characteristics and response to catheter ablation.
Authors: Wilber D J , Baerman J , Olshansky B , Kall J , Kopp D 
Published: June 2012

BACKGROUND
Sustained ventricular tachycardia in the absence of structural heart disease may have diverse mechanisms. Termination of the tachycardia by adenosine suggests triggered automaticity as the etiology in many of these patients. We examined the clinical characteristics, electrophysiological responses, and results of catheter ablation in this patient subgroup.

METHODS AND RESULTS
Intravenous adenosine terminated sustained ventricular tachycardia in seven of 14 consecutive patients without evidence of structural heart disease. In each of these patients, the tachycardia had a left bundle branch block, inferior-axis QRS configuration and occurred predominantly during stress or exertion. A morphologically similar sustained tachycardia was induced in six of seven patients during programmed ventricular stimulation, although day-to-day reproducibility was poor. Signal-averaged ECGs were normal in all patients. Imaging with 123I-metaiodobenzylguanidine did not reveal focal abnormalities in any of five patients. A discrete site of origin was identified in the free wall of the pulmonary infundibulum in all patients. Limited application of direct current shocks (two patients) or radiofrequency energy (five patients) resulted in long-term abolition of spontaneous and inducible ventricular tachycardia in all patients.

CONCLUSIONS
Adenosine-sensitive ventricular tachycardia appears to arise from relatively discrete sites predominantly located in the free wall of the pulmonary infundibulum. The localized nature of this tachycardia renders it amenable to long-term cure by catheter ablation techniques.
Inhibition of accelerated coronary atherosclerosis with dehydroepiandrosterone in the heterotopic rabbit model of cardiac transplantation.
Authors: Eich D M , Nestler J E , Johnson D E , Dworkin G H , Ko D , Wechsler A S , Hess M L 
Published: June 2012

BACKGROUND
Accelerated coronary atherosclerosis has become a critical problem in cardiac transplantation. Although the pathogenesis of this disease is unknown, hypercholesterolemia has been shown to be a major risk factor.

METHODS AND RESULTS
To study this problem, a hypercholesterolemic rabbit model of heterotopic cardiac transplantation was developed to study accelerated graft atherosclerosis. Based on suggestions in the literature, it was hypothesized that dehydroepiandrosterone (DHEA) may retard the progression of the disease. Using semiquantitative light microscopy, a predilection for the development of small vessel occlusive disease in the transplanted hearts was found. Chronic DHEA administration produced a 45% reduction in the number of significantly stenosed vessels in the transplanted hearts (p < 0.05) compared with controls and a 62% reduction in the nontransplanted hearts (p < 0.05), yielding an overall 50% reduction in the number of significantly stenosed vessels in both the transplanted and nontransplanted hearts. This reduction in luminal stenosis was observed in the absence of any significant alterations in lipid profiles.

CONCLUSIONS
It is concluded that chronic DHEA administration in a hypercholesterolemic rabbit model of heterotopic cardiac transplantation significantly retards the progression of accelerated atherosclerosis in both the transplanted heart and in the native heart.
Comparison of hemodynamic determinants for myocardial oxygen consumption under different contractile states in human ventricle.
Authors: Takaoka H , Takeuchi M , Odake M , Hayashi Y , Hata K , Mori M , Yokoyama M 
Published: June 2012

BACKGROUND
Recently, several indexes such as tension-time index (TTI), tension-time or force-time integral (FTI), rate-pressure product (RPP), pressure-work index (PWI), and systolic pressure-volume area (PVA) have been developed as predictors of myocardial oxygen consumption in experimental and clinical studies. However, it is still unclear whether these indexes are reliable predictors of myocardial oxygen consumption under various contractile states in human hearts.

METHODS AND RESULTS
We assessed the relation between TTI, FTI, RPP, PWI, and PVA and myocardial oxygen consumption per beat (VO2) in 13 patients with heart disease during volume loading. Left ventricular (LV) volume and pressure were measured simultaneously by the conductance catheter with the tipped micromanometer technique. VO2 was calculated from arterial coronary sinus oxygen content difference, and coronary sinus blood flow was measured by the thermodilution method. After z transformation of the correlation coefficients, mean z value for the VO2-PVA relation (1.83 +/- 0.60) was greater than those for the VO2-TTI relation (1.22 +/- 0.66; p < 0.005), VO2-FTI relation (1.18 +/- 0.61; p < 0.05), VO2-RPP relation (0.95 +/- 0.65; p < 0.05), and VO2-PWI relation (1.24 +/- 0.58; p < 0.05). During dobutamine infusion (5 micrograms.kg-1.min-1) in five of the 13 patients, VO2 also correlated best with PVA (z = 1.70 +/- 0.89) compared with TTI (z = 1.43 +/- 0.86), FTI (z = 1.48 +/- 0.95), RPP (z = 1.00 +/- 0.53), and PWI (z = 0.88 +/- 0.80). The contractile efficiency (38 +/- 14% to 38 +/- 20%), the reciprocal of the slope of the VO2-PVA relation, remained unchanged, whereas the VO2,PVA 0.8 (VO2 at PVA = 0.8 J per beat/100 g LV) increased from 1.48 +/- 1.16 to 2.06 +/- 1.13 J per beat/100 g LV (p < 0.05). These results show the parallel upward shift of the VO2-PVA relation during dobutamine infusion. Because increases in the VO2-intercept represent the VO2 for the increased excitation-contraction (E-C) coupling associated with the augmented contractile state, the parallelism of the VO2-PVA relation could discriminate between VO2 for mechanical work (PVA-dependent VO2) and VO2 for E-C coupling (PVA-independent VO2).

CONCLUSIONS
The results of the present study indicate that PVA is a reliable and valuable predictor of myocardial oxygen consumption under different contractile states in human hearts. The VO2-PVA relation could provide useful information about mechanoenergetics in diseased human hearts.