bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of porous infusion balloon-delivered angiopeptin on myointimal hyperplasia after balloon injury in the rabbit.
Authors: Hong M K , Bhatti T , Matthews B J , Stark K S , Cathapermal S S , Foegh M L , Ramwell P W , Kent K M 
Published: June 2012

BACKGROUND
Angiopeptin, a synthetic somatostatin analogue, reduces myointimal hyperplasia after experimental balloon angioplasty when given subcutaneously. The feasibility and efficacy of a single dose of angiopeptin delivered locally via the Wolinsky porous balloon on myointimal hyperplasia were studied.

METHODS AND RESULTS
Three rabbits received 125I-angiopeptin in the mid abdominal aorta via the Wolinsky balloon at 5 atm for 1 minute after balloon injury. Thirty minutes later, autoradiography demonstrated radioactivity in the media and the adventitia. Forty rabbits were divided equally into one control group receiving saline and three angiopeptin groups receiving 1, 10, or 100 micrograms/mL of angiopeptin delivered locally at 5 atm for 1 minute via the Wolinsky balloon into the mid abdominal aorta after balloon injury of the entire abdominal aorta. On day 21, the abdominal aortas were fixed in situ and harvested. There was no statistical difference in the amount of myointimal hyperplasia in the locally treated aorta in the angiopeptin groups compared with the control group. However, in the lower abdominal aorta, where balloon injury without local delivery was performed, there was a significant reduction of myointimal hyperplasia in the highest-concentration angiopeptin group (P < .001 versus the control group). Electron microscopy showed that the control animals had a pseudointima of smooth muscle cells throughout the aorta, whereas in all the angiopeptin-treated animals, endothelial cells were present at both locations.

CONCLUSIONS
Angiopeptin can be delivered intramurally via the Wolinsky porous balloon and reduces myointimal hyperplasia only in the area distal to the local drug delivery site (downstream effect), possibly by healing the injured endothelium, by transport via the vasa vasora, and/or by systemic effect.
Receptor-mediated cardioprotective effects of endogenous adenosine are exerted primarily during reperfusion after coronary occlusion in the rabbit.
Authors: Zhao Z Q , McGee S , Nakanishi K , Toombs C F , Johnston W E , Ashar M S , Vinten-Johansen J 
Published: June 2012

BACKGROUND
We hypothesized that: (1) endogenous adenosine released during ischemia/reperfusion reduces infarct size and preserves postischemic myocardial blood flow by receptor-mediated mechanisms and (2) this cardioprotection is exerted predominantly during reperfusion.

METHODS AND RESULTS
Sixty-one anesthetized open-chest rabbits subjected to 30 minutes of coronary occlusion and 120 minutes of reperfusion were randomized to six groups: group 1, saline (Vehicle) (n = 10) to allow receptor interaction of endogenous adenosine (Ado) during ischemia/reperfusion; group 2, Ado-receptor blockade during both ischemia and reperfusion with intravenous 8-p-sulfophenyltheophyl-line (10 mg/kg) (SPTIR, n = 10); group 3, Ado-receptor blockade in multiple doses during both ischemia and reperfusion (MSPTIR, n = 11); group 4, blockade during reperfusion (SPTR, n = 10); group 5, blockade during reperfusion with PD115,199 (6 mg/kg) (PDR, n = 10); and group 6, blockade after 30 minutes of reperfusion (SPT30R, n = 10) to allow adenosine receptor interaction during early reperfusion. Transmural myocardial blood flow in the area at risk (Ar) (15-microns radiolabeled microspheres) was reduced by 96.7% in all groups, from 137.9 +/- 15.5 to 4.5 +/- 1.4 mL.min-1 x 100 g-1 (P < .001). MSPTIR, SPTIR, and SPTR significantly attenuated reactive hyperemia at 15 minutes of reperfusion (144 +/- 18, 141 +/- 22, and 144 +/- 20 mL.min-1 x 100 g-1, respectively) compared with Vehicle (257 +/- 40 mL.min-1 x 100 g-1, P < .05). This attenuation was more pronounced in the necrotic zone than in the nonnecrotic zone. Reactive hyperemia at 15 minutes of reperfusion in SPT30R group was comparable to the Vehicle group. At 120 minutes of reperfusion, blood flow in Ar was significantly less in MSPTIR (77 +/- 10), SPTIR (82 +/- 9), and SPTR (80 +/- 11) compared with Vehicle (140 +/- 12) and SPT30R (105 +/- 24 mL.min-1 x 100 g-1). Infarct size (by triphenyltetrazolium chloride), expressed as a percent of Ar, was largest in the multiple-dose group with blockade during both ischemia and reperfusion (MSPTIR, 51.9 +/- 2.3%) and was significantly increased also in single-dose SPTIR (39.1 +/- 2.2%) compared with 25.7 +/- 1.7% in the Vehicle group (P < .05). Ado-receptor blockade only during reperfusion was associated with 14% smaller infarct size in the SPTR group than the MSPTIR group (P < .05). In contrast, Ado-receptor blockade after 30 minutes of reperfusion (SPT30R) did not increase infarct size (27.9 +/- 2.2%), which was comparable to infarct size in the Vehicle group.

CONCLUSIONS
We conclude that: (1) endogenous adenosine released from the myocardium during ischemia/reperfusion reduces infarct size by receptor-mediated mechanisms and (2) Ado-mediated cardioprotection is most pronounced during the early phase of reperfusion.
Circulating beta-atrial natriuretic factor in congestive heart failure in humans.
Authors: Wei C M , Kao P C , Lin J T , Heublein D M , Schaff H V , Burnett J C 
Published: June 2012

BACKGROUND
beta-Atrial natriuretic factor (beta-ANF) is an antiparallel dimer of alpha-ANF (alpha-ANF) with diminished cyclic GMP generation in vitro. To date, the presence of beta-ANF in the circulation of humans with severe congestive heart failure (CHF) remains controversial. The current study was designed to determine the presence and magnitude of circulating beta-ANF in severe CHF, to correlate plasma beta-ANF with the degree of ventricular dysfunction, and to investigate the role of human plasma and atrial tissue in the degradation of beta-ANF.

METHODS AND RESULTS
Venous plasma samples were obtained from patients (n = 12) with severe CHF and normal volunteers (n = 8). Total plasma ANF was measured by radioimmunoassay. alpha-ANF and beta-ANF in nonextracted plasma were separated by gel filtration chromatography using a P-6 column. Right atrial tissue samples (n = 5) were collected from a different group of patients at the time of open-heart surgery. 125I beta-ANF and I125 ANF were incubated with atrial tissue or plasma. The corresponding peak areas of beta-ANF were determined by Tamaya Digital Planimeter. beta-ANF represented 61% of total plasma ANF in CHF patients and was not detected in normal human plasma. The elevation of beta-ANF correlated with the severity of ventricular dysfunction. Thirty percent of beta-ANF and 100% alpha-ANF were converted to smaller peptide fragments in atrial tissue no conversion in plasma.

CONCLUSIONS
beta-ANF is the principal form of circulating ANF in patients with severe CHF and correlates with the degree of left ventricular dysfunction. beta-ANF is not generated from alpha-ANF and may be degraded rapidly in atrial tissue to smaller peptide fragments that do not occur in plasma. As beta-ANF is reported to have reduced biological action, the current studies may support the conclusion that the ANF system in CHF has reduced functional activity despite increases in circulation concentrations.
Role of K+ATP channels in coronary vasodilation during exercise.
Authors: Duncker D J , Van Zon N S , Altman J D , Pavek T J , Bache R J 
Published: June 2012

BACKGROUND
The mechanism of metabolic regulation of coronary vascular tone is still unclear. Therefore, we examined the role of vascular smooth muscle K+ATP channels in regulating coronary blood flow under resting conditions, during increments in myocardial metabolic demand produced by treadmill exercise, and in response to a brief ischemic stimulus.

METHODS AND RESULTS
Ten chronically instrumented dogs were studied at rest and during a four-stage exercise protocol under control conditions and during intracoronary infusion of the K+ATP channel blocker glibenclamide at rates of 10 and 50 micrograms.kg-1 x min-1. Glibenclamide (50 micrograms.kg-1 x min-1) decreased coronary blood flow at rest from 51 +/- 4 to 42 +/- 6 mL/min (P < .05), decreased myocardial oxygen consumption from 5.70 +/- 0.31 to 4.11 +/- 0.56 mL O2/min (P < .05), and decreased systolic wall thickening from 21 +/- 3% to 12 +/- 3% (P < .05). The depression of systolic wall thickening produced by glibenclamide was reversed when coronary blood flow was restored to the control level with intracoronary nitroprusside, indicating a primary effect of glibenclamide on coronary flow during resting conditions. However, glibenclamide did not impair the increases of coronary blood flow, myocardial oxygen consumption, and systolic wall thickening that occurred during exercise. In eight resting awake dogs, 50 micrograms.kg-1 x min-1 glibenclamide decreased the peak reactive hyperemia blood flow rate following a 20-second coronary occlusion from 149 +/- 14 mL/min during control conditions to 111 +/- 15 mL/min (P < .05), decreased the duration of reactive hyperemia from 49 +/- 6 to 33 +/- 3 seconds (P < .05), and decreased reactive hyperemia excess flow from 33 +/- 5 to 20 +/- 4 mL (P < .05).

CONCLUSIONS
These data demonstrate that K+ATP channels modulate coronary vasomotor tone under resting conditions and contribute to coronary vasodilation during ischemia. However, the coronary vasculature retains the capacity to dilate in response to increases in oxygen demand produced by exercise when K+ATP channels are blocked.
Increased risk of coronary heart disease death in men with low total and low-density lipoprotein cholesterol in the Russian Lipid Research Clinics Prevalence Follow-up Study.
Authors: Shestov D B , Deev A D , Klimov A N , Davis C E , Tyroler H A 
Published: June 2012

BACKGROUND
A continuously increasing risk of coronary heart disease with increasing levels of cholesterol has been reported by many observational and experimental studies. However, this type of association has not been observed in studies in the Russian Lipid Research Clinics.

METHODS AND RESULTS
Twelve-year coronary heart disease mortality among 40- to 59-year-old men was analyzed in the Moscow and St Petersburg examines in the Russian Lipid Research Clinics Program. The baseline survey examined 6431 men fasting and free of prevalent coronary heart disease. Lipids and lipoproteins, blood pressure, body mass, education level, alcohol intake, and smoking history were obtained. Mortality follow-up was based on contacts with participants or their relatives or neighbors. Coronary heart disease mortality was analyzed based on risk factor levels and was further divided into rapid and nonrapid deaths. A J-shaped cholesterol-coronary heart disease risk function was present for both total and low-density lipoprotein cholesterol. Further examination showed hypocholesterolemic men to have lower low-density and higher high-density lipoprotein cholesterol, higher alcohol consumption, leaner body mass, and less education than men with normal or high cholesterol levels. When education level was considered, the J-shaped risk function was present only among men with less than a high school education. When deaths were classified into rapid (less than 24 hours after onset of symptoms) and nonrapid, the J-shaped risk function was restricted to rapid deaths.

CONCLUSIONS
The results of disclose a sizeable subset of hypocholesterolemics in this population at increased risk of cardiac death associated with lifestyle characteristics.
Blunted nocturnal fall in blood pressure in hypertensive women with future cardiovascular morbid events.
Authors: Verdecchia P , Schillaci G , Gatteschi C , Zampi I , Battistelli M , Bartoccini C , Porcellati C 
Published: June 2012

BACKGROUND
In essential hypertension, a blunted or absent nocturnal fall in blood pressure (BP) may be associated with increased target organ damage. In this case-control study, we tested the hypothesis that an association exists between a blunted or absent nocturnal fall in BP and future cardiovascular morbid events in patients with essential hypertension.

METHODS AND RESULTS
Case subjects were 32 hypertensive patients with a first fatal or nonfatal major cardiovascular event who had off-therapy ambulatory BP monitoring 1 to 5 years earlier in the context of a registry of morbidity and mortality in hypertensive patients. Control subjects were 49 hypertensive patients free from cardiovascular events. The groups were matched with regard to date of baseline ambulatory BP monitoring, age, sex, clinic systolic and diastolic BP, and daytime ambulatory systolic and diastolic BP. At their baseline evaluation, cases and controls did not differ, in either sex, with respect to clinic BP (men, 164/100 vs 162/99 mmHg; women, 178/96 vs 180/93 mmHg), mean daytime ambulatory BP (men, 151/94 vs 147/95 mm Hg; women, 156/90 vs 158/89 mm Hg), age (men, 55 vs 56 years; women, 69 vs 68 years), sex, body weight, serum cholesterol, known duration and family history of hypertension, smoking habits, renal function, or prevalence of diabetes. Echocardiographic left ventricular mass, determined in a subset of patients, was greater in cases than in controls in men (145 vs 115 g/m2, P = .038) and women (137 vs 102 g/m2, P = .032). The time interval between baseline ambulatory BP monitoring and subsequent cardiovascular event (cases: mean, 2.1 years) or last contact with our center (controls: mean, 2.5 years) did not differ between the groups. In the baseline ambulatory BP profile, the nocturnal reductions of systolic and diastolic BP in men were 9% and 11%, respectively, in cases vs 9% and 12% in controls (all P = NS), whereas in women they were 3% and 8% in cases vs 11% and 16% in controls (P = .002/.004).

CONCLUSIONS
This retrospective case-control study suggests an association between the reduction or absence of the usual nocturnal fall in BP and future cardiovascular morbid events in white women with essential hypertension.
Thermolabile defect of methylenetetrahydrofolate reductase in coronary artery disease.
Authors: Kang S S , Passen E L , Ruggie N , Wong P W , Sora H 
Published: June 2012

BACKGROUND
To determine whether or not a moderate genetic defect of homocysteine metabolism is associated with the development of coronary artery disease, we studied the prevalence of thermolabile methylenetetrahydrofolate reductase, which is probably the most common genetic defect of homocysteine metabolism.

METHODS AND RESULTS
Three hundred thirty-nine subjects who underwent coronary angiography were classified into three groups: (1) patients with severe coronary artery stenosis (> or = 70% occlusion in one or more coronary arteries or > or = 50% occlusion in the left main coronary artery), (2) patients with mild to moderate coronary artery stenosis (< 70% occlusion in one or more coronary arteries or < 50% occlusion in the left main coronary artery), and (3) patients with non-coronary heart disease or noncardiac chest pain (nonstenotic coronary arteries). The thermolability of methylenetetrahydrofolate reductase was prospectively determined in all subjects. Plasma homocyst(e)ine levels were then measured in those with thermolabile methylenetetrahydrofolate reductase. The traditional risk factors for coronary artery disease were thereafter ascertained by chart review of all subjects. The prevalence of thermolabile methylenetetrahydrofolate reductase was 18.1% in group 1, 13.4% in group 2, and 7.9% in group 3. There was a significant difference between the prevalence of thermolabile methylenetetrahydrofolate reductase in groups 1 and 3 (P < .04). All individuals with thermolabile methylenetetrahydrofolate reductase irrespective of their clinical grouping had higher plasma homocyst(e)ine levels than normal (group 1, 14.86 +/- 5.85; group 2, 15.36 +/- 5.70; group 3, 13.39 +/- 3.80; normal, 8.50 +/- 2.8 nmol/mL). Nonetheless, there was no statistically significant difference in the plasma homocyst(e)ine concentrations of these patients with or without coronary artery stenosis. Using discriminant function analysis, thermolabile methylenetetrahydrofolate reductase was predictive of angiographically proven coronary artery stenosis. The traditional risk factors--age, sex, diabetes, smoking, hypercholesterolemia, and hypertension--were not significantly associated with the presence of thermolabile methylenetetrahydrofolate reductase.

CONCLUSIONS
Thermolabile methylenetetrahydrofolate reductase is a risk factor for coronary artery disease and is unrelated to other risk factors.
Effect of strenuous exercise on platelet activation state and reactivity.
Authors: Kestin A S , Ellis P A , Barnard M R , Errichetti A , Rosner B A , Michelson A D 
Published: June 2012

BACKGROUND
It has been hypothesized that platelets are activated, or made more activatible, by strenuous exercise and that these changes may play a role in the genesis of exercise-induced coronary ischemia. Previous studies have yielded conflicting results but have used assays (eg, platelet aggregation, plasma platelet factor 4, and plasma beta-thromboglobulin) that are subject to methodological problems.

METHODS AND RESULTS
In the present study, a whole blood flow cytometric method was used to study the platelet activation state and reactivity of 12 physically active and 12 sedentary individuals before and after standardized treadmill exercise testing. The peptide gly-pro-arg-pro (GPRP) was included in this assay to prevent fibrin polymerization and platelet aggregation, thus allowing the measurement of the reactivity to thrombin of individual platelets in the physiological milieu of whole blood. A panel of fluorescent-labeled monoclonal antibodies was used to monitor activation-dependent platelet surface changes: downregulation of glycoprotein (GP) Ib (6D1) and upregulation of GMP-140 (S12), the GPIIb-IIIa complex (PAC1), and GPIV (OKM5). In samples obtained before exercise, platelets not exposed to thrombin showed no evidence of in vitro activation. In the sedentary subjects, exercise caused a consistent and significant augmentation of the platelet activation state and reactivity as judged by the binding of 6D1 in the presence of thrombin 0.05 U/mL (P < .001), 0.005 U/mL (P = .001), and 0 U/mL (P = .004) and by the binding of OKM5 in the presence of thrombin 0.05 U/mL (P < .001), 0.005 U/mL (P = .029), and 0 U/mL (P = .035). Exercise increased the binding of PAC1 at only a single thrombin concentration (0.005 U/mL, P = .027) and did not alter the binding of S12 at any thrombin concentration. In contrast, in the physically active subjects, exercise failed to cause a consistent alteration in either platelet activation state or platelet reactivity. No significant differences were found between the 12 male and 12 female volunteers.

CONCLUSIONS
Strenuous exercise in sedentary subjects but not physically active subjects resulted in both platelet activation and platelet hyperreactivity. These changes were more readily detected with monoclonal antibodies directed against GPIb (6D1) and, to a lesser extent, GPIV (OKM5) rather than those directed against the GPIIb-IIIa complex (PAC1) and GMP-140 (S12). Platelet activation by thrombin, generally regarded as the most physiologically important agonist, can be studied in whole blood in a clinical setting through the use of the peptide GPRP.
Abnormalities of sodium handling and of cardiovascular adaptations during high salt diet in patients with mild heart failure.
Authors: Volpe M , Tritto C , DeLuca N , Rubattu S , Rao M A , Lamenza F , Mirante A , Enea I , Rendina V , Mele A F 
Published: June 2012

BACKGROUND
Sodium retention and hormonal activation are fundamental hallmarks in congestive heart failure. The present study was designed to assess the ability of patients with asymptomatic to mildly symptomatic heart failure and no signs or symptoms of congestion to excrete ingested sodium and to identify possible early abnormalities of hormonal and hemodynamic mechanisms related to sodium handling.

METHODS AND RESULTS
The effects of a high salt diet (250 mEq/day for 6 days) on hemodynamics, salt-regulating hormones, and renal excretory response were investigated in a balanced study in 12 untreated patients with idiopathic or ischemic dilated cardiomyopathy and mild heart failure (NYHA class I-II, ejection fraction < 50%) (HF) and in 12 normal subjects, who had been previously maintained a 100 mEq/day NaCl diet. In normal subjects, high salt diet was associated with significant increases of echocardiographically measured left ventricular end-diastolic volume, ejection fraction, and stroke volume (all P < .001) and with a reduction of total peripheral resistance (P < .001). In addition, plasma atrial natriuretic factor (ANF) levels increased (P < .05), and plasma renin activity and aldosterone concentrations fell (both P < .001) in normals in response to salt excess. In HF patients, both left ventricular end-diastolic and end-systolic volumes increased in response to high salt diet, whereas ejection fraction and stroke volume failed to increase, and total peripheral resistance did not change during high salt diet. In addition, plasma ANF levels did not rise in HF in response to salt loading, whereas plasma renin activity and aldosterone concentrations were as much suppressed as in normals. Although urinary sodium excretions were not significantly different in the two groups, there was a small but systematic reduction of daily sodium excretion in HF, which resulted in a significantly higher cumulative sodium balance in HF than in normals during the high salt diet period (P < .001).

CONCLUSIONS
These results show a reduced ability to excrete a sodium load and early abnormalities of cardiac and hemodynamic adaptations to salt excess in patients with mild heart failure and no signs or symptoms of congestion.
Induction of right ventricular hypertrophy with obstructing balloon catheter. Nonsurgical ventricular preparation for the arterial switch operation in simple transposition.
Authors: Katayama H , Krzeski R , Frantz E G , Ferreiro J I , Lucas C L , Ha B , Henry G W 
Published: June 2012

BACKGROUND
Recently, a successful result with a rapid two-stage arterial switch operation (ASO) was reported for patients with transposition of the great arteries (TGA) with low left ventricular pressure. In this procedure, the interval between pulmonary arterial banding and ASO was approximately 1 week. This successful result indicates the possibility of a nonsurgical ventricular preparation procedure using an obstructing balloon catheter prior to ASO.

METHODS AND RESULTS
A 5F atrioseptostomy catheter was inserted directly into the main pulmonary artery in six lambs aged 20 to 38 days. After the chest was closed, the balloon was inflated twice a day for a period of 2 to 2.5 hours. This procedure was performed for 4 consecutive days. After the final inflation, the ratio of right ventricular weight to total ventricular weight was compared with that in an age-matched control group. After the final inflation, the peak systolic right ventricular pressure and the percentage of peak systolic right ventricular to peak systolic aortic pressure rose to 85.6 +/- 4.7 mm Hg (mean +/- 1 SD) and 79.6 +/- 8.6%, respectively. The percentages of the right ventricular weight to the total ventricular weight were significantly higher after the balloon inflation than those in the control group in terms of wet heart weight (29.5 +/- 1.2% versus 23.0 +/- 1.0%; P < .0001) and dry heart weight (27.0 +/- 2.0% versus 21.0 +/- 1.1%; P < .0001).

CONCLUSIONS
The myocardial mass in the right ventricle increased after 4 days of intermittently applied pressure overload. Nonsurgical preparation of the ventricle for ASO in TGA is feasible.