bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhaled nitric oxide in congenital heart disease.
Authors: Roberts J D , Lang P , Bigatello L M , Vlahakes G J , Zapol W M 
Published: June 2012

BACKGROUND
Congenital heart lesions may be complicated by pulmonary arterial smooth muscle hyperplasia, hypertrophy, and hypertension. We assessed whether inhaling low levels of nitric oxide (NO), an endothelium-derived relaxing factor, would produce selective pulmonary vasodilation in pediatric patients with congenital heart disease and pulmonary hypertension. We also compared the pulmonary vasodilator potencies of inhaled NO and oxygen in these patients.

METHODS AND RESULTS
In 10 sequentially presenting, spontaneously breathing patients, we determined whether inhaling 20-80 ppm by volume of NO at inspired oxygen concentrations (FIO2) of 0.21-0.3 and 0.9 would reduce the pulmonary vascular resistance index (Rp). We then compared breathing oxygen with inhaling NO. Inhaling 80 ppm NO at FIO2 0.21-0.3 reduced mean pulmonary artery pressure from 48 +/- 19 to 40 +/- 14 mm Hg and Rp from 658 +/- 421 to 491 +/- 417 dyne.sec.cm-5.m-2 (mean +/- SD, both p < 0.05). Increasing the FIO2 to 0.9 without adding NO did not reduce mean pulmonary artery pressure but reduced Rp and increased the ratio of pulmonary to systemic blood flow (Qp/Qs), primarily by increasing Qp (p < 0.05). Breathing 80 ppm NO at FIO2 0.9 reduced mean pulmonary artery pressure and Rp to the lowest levels and increased Qp and Qp/Qs (all p < 0.05). While breathing at FIO2 0.9, inhalation of 40 ppm NO reduced Rp (p < 0.05); the maximum reduction of Rp occurred while breathing 80 ppm NO. Inhaling 80 ppm NO at FIO2 0.21-0.9 did not alter mean aortic pressure or systemic vascular resistance. Methemoglobin levels were unchanged by breathing up to 80 ppm NO for 30 minutes.

CONCLUSIONS
Inhaled NO is a potent and selective pulmonary vasodilator in pediatric patients with congenital heart disease complicated by pulmonary artery hypertension. Inhaling low levels of NO may provide an important and safe means for evaluating the pulmonary vasodilatory capacity of patients with congenital heart disease without producing systemic vasodilation.
Altered expression of beta-adrenergic receptor kinase and beta 1-adrenergic receptors in the failing human heart.
Authors: Ungerer M , Böhm M , Elce J S , Erdmann E , Lohse M J 
Published: June 2012

BACKGROUND
In chronic heart failure, the positive inotropic effects of beta-adrenergic receptor agonists are greatly reduced, in part as a result of two alterations of the cardiac beta-adrenergic receptors: loss of their function (receptor uncoupling) and reduction of their number (downregulation). In vitro studies have shown that a major mechanism leading to beta-adrenergic receptor uncoupling involves phosphorylation of the receptors by the specific beta-adrenergic receptor kinase (beta ARK).

METHODS AND RESULTS
We have therefore investigated expression of beta ARK and beta-adrenergic receptors in samples from the left ventricles of patients with dilated cardiomyopathy or ischemic cardiomyopathy and from nonfailing control ventricles. Contractile responses to beta-receptor stimulation were decreased in the failing hearts compared with control hearts, whereas those to forskolin and calcium remained unchanged. The messenger RNA (mRNA) levels of beta ARK, beta 1- and beta 2-receptors, and of glyceraldehyde phosphate dehydrogenase and beta-actin as controls were measured by quantitative polymerase chain reactions. In addition, beta ARK enzyme activity assays were performed, and the levels of beta 1- and beta 2-receptors were determined by radioligand binding. beta ARK mRNA levels were increased almost threefold in both forms of heart failure, and beta ARK activity was enhanced. beta 1-Receptor mRNA levels and beta 1-receptor numbers were decreased by approximately 50% in both failing groups, whereas these levels were unaltered for beta 2-receptors. There were no differences between dilated and ischemic cardiomyopathy for any of these parameters.

CONCLUSIONS
In addition to other alterations found in failing hearts, the diminished response to beta-receptor agonists appears to involve the combined effects of enhanced expression of beta ARK and reduced expression of beta 1-receptors.
Direct comparison of [13N]ammonia and [15O]water estimates of perfusion with quantification of regional myocardial blood flow by microspheres.
Authors: Bol A , Melin J A , Vanoverschelde J L , Baudhuin T , Vogelaers D , De Pauw M , Michel C , Luxen A , Labar D , Cogneau M 
Published: June 2012

BACKGROUND
Both [13N]ammonia and [15O]water have been used to quantify myocardial blood flow with positron emission tomography using appropriate tracer kinetic models. A direct comparison of the two tracers with radioactive microspheres has not been performed in the same experimental preparation.

METHODS AND RESULTS
The two tracers have been tested for myocardial blood flow quantification in closed-chest dogs with circumflex coronary stenosis or permanent occlusion at rest and during adenosine-induced hyperemia. [13N]ammonia- and [15O]water-derived myocardial blood flow values have been compared with radiolabeled microspheres. Validation studies consisted of simultaneous measurements of blood flow with positron emission tomography and microspheres over a wide range of flow values. Blood pool and regional tissue activity curves were fitted with a three-compartment model for [13N]ammonia with and without arterial metabolite correction and with a single-tissue-compartment model for [15O]water. A correction for finite-resolution effect before the fit was also applied. In large regions of interest (5 cm3), a good correlation between the microsphere method and [13N]ammonia (with metabolite correction) was obtained (y = 3 + 0.78x, r = 0.94). The correlation with microspheres was slightly better with [15O]water (y = -3 + 0.89x, r = 0.97). Similar correlations were achieved in smaller regions of interest (1 cm3) as well as in akinetic segments and in central infarct regions.

CONCLUSIONS
Positron emission tomography with appropriate tracer kinetic models using [13N]ammonia and [15O]water provides an accurate quantitative method for measuring regional myocardial blood flow over a wide range of flow values in normally contracting or akinetic canine myocardium in the absence and in the presence of infarction.
Role of coronary artery spasm in progression of organic coronary stenosis and acute myocardial infarction in a swine model. Importance of mode of onset and duration of coronary artery spasm.
Authors: Kuga T , Tagawa H , Tomoike H , Mitsuoka W , Egashira S , Ohara Y , Takeshita A , Nakamura M 
Published: June 2012

BACKGROUND
Coronary spasm may play an important role in progression of organic coronary stenosis and myocardial infarction, but the mechanisms responsible for these complications are not known. This study aimed to examine whether the mode of onset and the duration of coronary spasm influenced progression of organic coronary stenosis and acute myocardial infarction in a swine model of coronary spasm.

METHODS AND RESULTS
Göttingen miniature pigs were subjected to cholesterol feeding, balloon-induced coronary arterial denudation, and x-ray irradiation. Five months later, coronary spasm was induced by intracoronary injection of serotonin. In 10 pigs, coronary spasm was provoked abruptly and maintained for 25 minutes by five repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes (group A, abrupt onset and short duration). In group B, coronary spasm was provoked gradually by intracoronary injections of serotonin at graded doses of 0.1, 0.3, and 0.6 microgram/kg every 5 minutes and was then maintained for 25 minutes in four pigs (group B1, gradual onset and short duration) and for 120 minutes in six pigs (group B2, gradual onset and long duration) by repeated intracoronary injections of serotonin (10 micrograms/kg) every 5 minutes. Intramural hemorrhage was noted histologically at the spastic site more frequently in group A with abrupt onset (nine of 10 pigs) than in group B with gradual onset (two of 10 pigs) (p < 0.01). Progression of organic coronary stenosis due to intramural hemorrhage was noted in seven pigs (six pigs in group A and one pig in group B), including three cases of total coronary occlusion. Evidence for the evolution of acute myocardial infarction (serial ECG findings, left ventriculograms, and histological findings) was noted in one pig (7%) of group A or B1 with short duration and in five of six pigs (83%) in group B2 with long duration (p < 0.01 versus group A and B1).

CONCLUSIONS
These results indicate that: 1) intramural hemorrhage was frequently induced by coronary spasm of abrupt but not of gradual onset, 2) intramural hemorrhage resulted in acute progression of coronary stenosis and sometimes resulted in persistent total coronary occlusion leading to acute myocardial infarction, and 3) prolonged coronary spasm resulted in acute myocardial infarction without progression of organic coronary stenosis.
Results of percutaneous transluminal coronary angioplasty in women. 1985-1986 National Heart, Lung, and Blood Institute's Coronary Angioplasty Registry.
Authors: Kelsey S F , James M , Holubkov A L , Holubkov R , Cowley M J , Detre K M 
Published: June 2012

BACKGROUND
The National Heart, Lung, and Blood Institute (NHLBI) Percutaneous Transluminal Coronary Angioplasty (PTCA) 1978-1981 Registry cohort indicated that PTCA risk was higher and efficacy was lower in women. Data from the 1985-1986 PTCA Registry are used to address the question of whether compared with men, women still have a worse outcome after PTCA.

METHODS AND RESULTS
The 1985-1986 NHLBI PTCA Registry collected data on consecutive, first-PTCA cases at 16 centers. Initial results are reported for 2,136 patients, 546 of whom were women. Four-year follow-up status was available on 95% of the cohort. Although women were an average of 4.5 years older than the male patients and had more cardiovascular risk factors and more severe angina, their coronary artery disease as assessed by angiography was not more extensive. Rates of angiographic success on a per-lesion basis were similar for women and men (89% versus 88%), and the clinical success rates (79%) were the same. Women had more initial complications (29% versus 20%, p < 0.001) and a considerably higher procedural mortality rate (2.6% versus 0.3%, p < 0.001). For patients who survived the initial procedure, 4-year survival was similar for men and women. At 4 years, women had slightly fewer events (myocardial infarction, repeat PTCA, and/or coronary artery bypass grafting). Despite the higher proportion of women reporting the presence of angina and medication use at 4 years, the proportion reporting improvement in symptomatic status was similar to that of men.

CONCLUSIONS
Women undergoing PTCA have a higher procedural mortality risk than men; this is explained in part by their worse cardiovascular risk factor profile. Otherwise, the success rate and long-term prognosis after PTCA are excellent, and PTCA should be considered for women in need of revascularization.
Comparison of angioplasty and surgery for unoperated coarctation of the aorta.
Authors: Shaddy R E , Boucek M M , Sturtevant J E , Ruttenberg H D , Jaffe R B , Tani L Y , Judd V E , Veasy L G , McGough E C , Orsmond G S 
Published: June 2012

BACKGROUND
The use of balloon coarctation angioplasty instead of surgery as treatment for unoperated coarctation of the aorta is controversial. The efficacy and complications of the two procedures have not been studied before in a prospective fashion.

METHODS AND RESULTS
Thirty-six patients were prospectively randomized to either angioplasty (20 patients) or surgery (16 patients). Immediate results and patient follow-up, including physical examination, angiograms, and magnetic resonance imaging, were compared between groups. Reduction in peak systolic pressure gradient across the coarctation was similar (86%) immediately after both balloon coarctation angioplasty and surgery. On follow-up, aneurysms were seen only in the angioplasty group (20%) and not in the surgery group (0%). No aneurysms have shown progression or required surgery. The incidence of other complications was similar in both groups, although two patients experienced neurological complications after surgery. Although not statistically different, the incidence of restenosis (peak systolic pressure gradient > or = 20 mm Hg) tended to be greater in the angioplasty group (25%) than in the surgery group (6%). Restenosis after angioplasty occurred more frequently in patients with an aortic isthmus/descending aorta diameter ratio < 0.65 and was associated with an immediate catheterization residual peak systolic pressure gradient across the coarctation > or = 12 mm Hg.

CONCLUSIONS
Immediate gradient reduction is similar after balloon coarctation angioplasty and surgical treatment of unoperated coarctation of the aorta. The risks of aneurysm formation and possibly restenosis after angioplasty are higher than after surgery, although the risks of other complications are similar. Balloon coarctation angioplasty may provide an effective initial alternative to surgical repair of unoperated coarctation of the aorta in children beyond infancy, particularly in patients with a well-developed isthmus. Further follow-up is necessary to determine the long-term risks of postangioplasty aneurysms.
Abnormal baroreceptor-mediated vasodilation of the peripheral circulation in congestive heart failure secondary to idiopathic dilated cardiomyopathy.
Authors: Wroblewski H , Kastrup J , Mortensen S A , Haunsø S 
Published: June 2012

BACKGROUND
Peripheral edema is a major clinical problem in congestive heart failure (CHF). The function of the edema-protective baroreceptor-mediated and local nervous vasoconstrictor reflexes of the lower leg during orthostasis in moderate and severe CHF has largely been unexplored.

METHODS AND RESULTS
Baroreceptor-mediated and local nervous regulation of subcutaneous blood flow of the lower leg was studied in healthy subjects and in patients with moderate and severe CHF secondary to idiopathic dilated cardiomyopathy. Blood flow was measured by the local 133Xe washout method in the supine position and during 45 degrees head-up tilt. When the central baroreceptor reflex alone was activated, the changes in subcutaneous blood flow of the heart failure patients in both groups were significantly different from those of the eleven control subjects: blood flow increased 48 +/- 26% in 10 severe and 3 +/- 24% in nine moderate CHF patients compared with the decrease in blood flow of -36 +/- 15% observed in 11 control subjects (p < 0.0001 for both). A highly significant direct association was demonstrated between changes in blood flow and New York Heart Association functional class (p = 0.007) and the left ventricular ejection fraction (p = 0.01). Activation of the baroreceptor and local venoarteriolar axon reflexes simultaneously increased blood flow significantly (30 +/- 9%) in 14 patients with severe CHF, compared with the decrease found in 14 control subjects (-53 +/- 9%) and in the group of 14 patients with moderate CHF (-17 +/- 25%) (p < 0.0001 for both).

CONCLUSIONS
Patients with CHF secondary to idiopathic dilated cardiomyopathy have an abnormal baroreceptor-mediated vasodilation in subcutaneous tissue of the lower leg during the upright position, which increases with the severity of the disease. The hemodynamic consequence is capillary hypertension and hyperemia in the leg during the upright position that may contribute to the development of edema and to the initiation of structural changes (microangiopathy) demonstrated in the microcirculation.
Regional ischemic 'preconditioning' protects remote virgin myocardium from subsequent sustained coronary occlusion.
Authors: Przyklenk K , Bauer B , Ovize M , Kloner R A , Whittaker P 
Published: June 2012

BACKGROUND
One or more brief episodes of coronary artery occlusion protect or "precondition" the myocardium perfused by that artery from a subsequent episode of sustained ischemia. We sought to determine whether ischemic preconditioning protects only those myocytes subjected to brief coronary occlusion or whether brief occlusions in one vascular bed also limit infarct size and/or attenuate contractile dysfunction in remote virgin myocardium subjected to subsequent sustained coronary occlusion.

METHODS AND RESULTS
In the preliminary limb of the study, six anesthetized dogs underwent four episodes of 5-minute circumflex branch occlusion plus 5-minute reperfusion, followed by 1 hour of sustained left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow during left anterior descending coronary artery occlusion (measured by injection of radiolabeled microspheres) was 0.07 +/- 0.03 mL.min-1 x g tissue-1, similar to the value of 0.07 +/- 0.02 mL.min-1 x g-1 observed in a group of eight concurrent control dogs. However, infarct size (assessed by triphenyltetrazolium staining) in the circumflex preconditioned group averaged 4 +/- 1% of the myocardium at risk, significantly less (p < 0.05) than the value of 13 +/- 4% observed in the concurrent controls. An additional 18 dogs were then randomized to undergo either four episodes of circumflex branch occlusion (n = 8) or no intervention (n = 10) before 1 hour of left anterior descending coronary artery occlusion and 4.5 hours of reflow. Subendocardial blood flow averaged 0.08 +/- 0.02 versus 0.08 +/- 0.03 mL.min-1 x g-1 in the control versus circumflex preconditioned groups, yet infarct size was significantly smaller in circumflex preconditioned dogs than in the controls (6 +/- 2% versus 16 +/- 5% of the risk region; p < 0.05). At 4.5 hours following reperfusion, segment shortening in the left anterior descending coronary artery bed (assessed by sonomicrometry) averaged -21 +/- 19% of baseline in control animals versus 13 +/- 12% of baseline in the preconditioned group (p = NS). Circumflex preconditioning did not, however, have an independent beneficial effect on contractile function: Regression analysis revealed that the trend toward improved function in circumflex preconditioned dogs reflected the smaller infarct sizes in this group.

CONCLUSIONS
Brief episodes of ischemia in one vascular bed protect remote, virgin myocardium from subsequent sustained coronary artery occlusion in this canine model. These data imply that preconditioning may be mediated by factor(s) activated, produced, or transported throughout the heart during brief ischemia/reperfusion.
The renin-angiotensin system and volume overload-induced cardiac hypertrophy in rats. Effects of angiotensin converting enzyme inhibitor versus angiotensin II receptor blocker.
Authors: Ruzicka M , Yuan B , Harmsen E , Leenen F H 
Published: June 2012

BACKGROUND
The degree of cardiac hypertrophy is not only load dependent: Among other factors, the renin-angiotensin system may play a role in the regulation of cardiac myocyte growth.

METHODS AND RESULTS
To evaluate the role of the renin-angiotensin system in volume overload-induced cardiac hypertrophy, we assessed: 1) the time course of changes in cardiac hemodynamics, cardiac anatomy, and plasma and cardiac renin activity in response to volume overload induced by two sizes of abdominal aortocaval shunt and 2) the effects of chronic treatment with an angiotensin converting enzyme inhibitor (ACEI) versus an angiotensin II receptor blocker on hemodynamics and cardiac hypertrophy. Drug treatment started 3 days before shunt surgery. An increase in left ventricular end-diastolic pressure (LVEDP) and the development of right ventricular (RV) and left ventricular (LV) eccentric hypertrophy in response to volume overload occurred within the first week after induction of the shunt. Plasma renin activity (PRA) and cardiac renin activity peaked shortly after induction of the shunt. During the chronic phase, LVEDP and PRA decreased somewhat but remained significantly elevated up to 7 weeks after shunt surgery. Cardiac renin activity returned toward normal within 4 weeks after surgery. Treatment with the ACEI enalapril caused only a modest decrease in LV internal diameter but did not affect increases in LV and RV weights in response to volume overload despite a major decrease in LVEDP after chronic treatment. In contrast, treatment with the angiotensin II receptor blocker losartan, which had similar effects on cardiac and peripheral hemodynamics, prevented dilation of the LV after 7 days and attenuated the dilation of the LV after 28 days. Moreover, increases in LV and RV weights were significantly attenuated by losartan.

CONCLUSIONS
The development of volume overload-induced cardiac hypertrophy is associated with significant increases in PRA and cardiac renin activity shortly after induction of an aortocaval shunt. Whereas the two blockers of the renin-angiotensin system decreased LVEDP to a similar extent, only the angiotensin II receptor blocker blunted the hypertrophic response of the heart to volume overload, which is indicative for other than hemodynamic determinants of the cardiac hypertrophic response. One trophic factor may be cardiac angiotensin II generated via an angiotensin II-forming enzyme resistant to ACEI and possibly activated by cardiac volume overload.