bluuebunny/crossref_metadata_2025_split huggingface dataset:
Changes in passive mechanical stiffness of myocardial tissue with aneurysm formation.
Authors: Gupta K B , Ratcliffe M B , Fallert M A , Edmunds L H , Bogen D K 
Published: June 2012

BACKGROUND
Myocardium undergoes complex cellular and histochemical alterations after acute myocardial infarction. These structural changes directly affect the mechanical stiffness of infarcted and remote myocardia. Previous investigations of infarct stiffness have been limited to uniaxial testing, which does not provide a unique description of the tissue's three-dimensional material properties. This study describes the first serial measurements of biaxial mechanical properties of sheep myocardium after anteroapical infarction.

METHODS AND RESULTS
Anteroapical infarctions of 23.7 +/- 2.5% of the left ventricular mass were produced by coronary arterial ligation in sheep. Biaxial force-extension measurements were made on freshly excised squares (6.45 cm2) of remote, noninfarcted, and infarcted myocardia before and 4 hours, 1 week, 2 weeks, and 6 weeks after ligation. Adjacent myocardial samples were assayed for hydroxyproline content. Force-extension data and a derived constitutive equation were used to describe stresses and strains and material properties of each sample. In sheep, anteroapical infarctions evolve into thin left ventricular aneurysms that consist of predominantly fibrous tissue with disrupted groups of muscle cells encased in scar. In the infarct, Cauchy stresses at 15% extensions (control stresses: circumferential, sigma C, 19.4 +/- 3.3 g/cm2; longitudinal, sigma L, 54.8 +/- 34.8 g/cm2) increase within 4 hours, peak at 1 to 2 weeks (sigma C, 338.5 +/- 143.6 g/cm2; sigma L, 310.7 +/- 45.9 g/cm2), and then decrease 6 weeks after infarction (sigma C, 115 +/- 47.2 g/cm2; sigma L, 53.2 +/-28.9 g/cm2). Stresses in the remote myocardium follow a similar time course but to a lesser extent than the infarcted region. Hydroxyproline content, a measure of collagen content, does not correlate with infarct stiffness but progressively increases to 69.7 +/- 7.6 micrograms/mg after 6 weeks. Stress-extension curves demonstrate directional anisotropy of both infarcted and remote myocardia.

CONCLUSIONS
The findings indicate that infarcted myocardium becomes more stiff during the first 1 to 2 weeks after anteroapical infarction and then more compliant. The infarct also exhibits directional anisotropy. These observations underscore the importance of ventricular material properties during the remodeling process after acute myocardial infarction and may partially explain the progressive left ventricular dilatation and functional deterioration that occur in some patients after anteroapical infarction.
An enantiomer-enantiomer interaction of (S)- and (R)-propafenone modifies the effect of racemic drug therapy.
Authors: Kroemer H K , Fromm M F , Bühl K , Terefe H , Blaschke G , Eichelbaum M 
Published: June 2012

BACKGROUND
Therapy with racemic compounds produces effects that can be attributed to both (S)- and (R)-enantiomers. Here we have tested the hypothesis that an enantiomer-enantiomer interaction would modulate the effects of treatment with a racemate, the antiarrhythmic propafenone. Previous studies have shown that while the enantiomers of propafenone exert similar sodium channel-blocking (QRS widening) effects, it is the (S)-enantiomer that produces beta-blockade; moreover, we have demonstrated recently that (R)-propafenone inhibits the metabolism of (S)-propafenone in vitro.

METHODS AND RESULTS
This single-blind, randomized study compared the effects of (R/S)-, (S)-, (R)-propafenone (150 mg q 6 hours for 4 days) and placebo on QRS duration (delta QRS) and on maximum exercise heart rate (delta HRmax), an index of beta-blockade. The clearance of (S)-propafenone was significantly lower (-55 +/- 24%, P < .001) during treatment with (R/S)-propafenone than with the (S)-enantiomer alone, and delta HRmax was significantly altered during (R/S)-propafenone (-8.8 +/- 6.6 beats per minute; P < .01) and during (S)-propafenone (-4.3 +/- 4.8 beats per minute; P < .01) but not during (R)-propafenone (-1.8 +/- 6.4 beats per minute) or placebo (0.3 +/- 7.1 beats per minute). In contrast, (R/S)-, (S)-, and (R)-propafenone all prolonged QRS compared with placebo.

CONCLUSIONS
These data indicate that (R)-propafenone impairs the disposition of (S)-propafenone in humans. As a result, the beta-blocking effects of 150 mg of racemic propafenone (75 mg of the [S]-enantiomer) were more pronounced than those of 150 mg of (S)-propafenone alone. Thus, the effects of racemic drug therapy are not necessarily those predicted by summation of the effects of the individual enantiomers.
Novel cardiac myofilament desensitizing factor released by endocardial and vascular endothelial cells.
Authors: Shah A M , Mebazaa A , Wetzel R C , Lakatta E G 
Published: June 2012

BACKGROUND
Recent studies suggest that both endocardial endothelium and coronary vascular endothelium influence myocardial contraction, but the mediators responsible and their mechanisms of action are not well defined.

METHODS AND RESULTS
We investigated the effects of cultured endocardial endothelial and vascular endothelial cell superfusate on contraction and intracellular calcium transients of isolated rat cardiac myocytes. Endothelial cell superfusate induced a potent negative inotropic effect, with a rapid reversible decrease in myocyte twitch amplitude, earlier twitch relaxation, and a significant increase in diastolic length. This effect was not associated with significant changes in intracellular calcium or pH; was not attributable to nitric oxide, prostanoids, cGMP, or protein kinase C activation; and did not involve pertussis toxin-sensitive G proteins. The activity was stable at 37 degrees C for several hours, was not destroyed by protease treatment, and was found in low-molecular-weight (< 1 kD) superfusate fractions.

CONCLUSIONS
These data suggest the tonic release by endothelial cells of a novel, stable factor that acts predominantly by reducing the response of cardiac myofilaments to calcium (ie, "desensitizes" them). This "desensitizing factor" could rapidly modulate cardiac contraction-relaxation coupling and diastolic tonus and exert distant effects because of its stability.
Reduction in serum cholesterol with pravastatin improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.
Authors: Egashira K , Hirooka Y , Kai H , Sugimachi M , Suzuki S , Inou T , Takeshita A 
Published: June 2012

BACKGROUND
This study aimed to determine if cholesterol-lowering therapy improves endothelium-dependent coronary vasomotion in patients with hypercholesterolemia.

METHODS AND RESULTS
Nine patients with hypercholesterolemia were studied before and after cholesterol-lowering therapy with pravastatin (an inhibitor of HMG-CoA reductase) for 6 +/- 3 months, which lowered serum cholesterol from 272 +/- 8 to 187 +/- 16 mg/dL (P < .01). Control patients with serum cholesterol of 218 +/- 23 mg/dL also were studied twice in a similar interval (8 +/- 2 months) with no cholesterol-lowering drugs. Acetylcholine (the endothelium-dependent vasodilator) and papaverine and nitrate (endothelium-independent vasodilators) were infused into the study coronary artery. Changes in the diameter of the epicardial coronary artery and coronary blood flow were assessed by quantitative coronary arteriography and an intracoronary Doppler catheter. In patients with hypercholesterolemia, acetylcholine-induced vasoconstriction of the epicardial artery was less (P < .05) and the acetylcholine-induced increases in coronary blood flow were greater (P < .001) after than before pravastatin. In control patients, responses of the epicardial coronary artery and coronary blood flow to acetylcholine did not change over the follow-up period. The vasomotor responses to papaverine or nitrate were similar between the two groups, and no interval changes in their responses were noted in either group.

CONCLUSIONS
These results suggest that cholesterol-lowering therapy with pravastatin may improve endothelium-dependent coronary vasomotion, which may possibly contribute to the improvement of myocardial perfusion as well as the regression of coronary atherosclerosis.
Physical activity and 23-year incidence of coronary heart disease morbidity and mortality among middle-aged men. The Honolulu Heart Program.
Authors: Rodriguez B L , Curb J D , Burchfiel C M , Abbott R D , Petrovitch H , Masaki K , Chiu D 
Published: June 2012

BACKGROUND
The purpose of the study was to examine the association between physical activity and 23-year incidence of coronary heart disease morbidity and mortality. This cohort study continues to follow 8006 Japanese-American men who were 45 to 68 years of age and living on Oahu, Hawaii, in 1965, for the development of coronary heart disease morbidity and mortality.

METHODS AND RESULTS
The Framingham physical activity index was calculated by summing the product of average hours spent at each activity level and a weighting factor based on oxygen consumption. Study subjects were divided into tertiles of physical activity index at baseline. Relative risks and 95% confidence intervals (CI) for incidence of coronary heart disease morbidity and mortality were obtained using the Cox model. After age adjustment and using the lowest physical activity index tertile as a reference group, the relative risk for coronary heart disease incidence for the highest tertile of physical activity was 0.83 (CI, 0.70 to 0.99). After adjusting for age, hypertension, smoking, alcohol intake, diabetes, cholesterol, and body mass index, the relative risk was 0.95 and CI included 1 (CI, 0.80 to 1.14). For coronary heart disease mortality, the age-adjusted relative risk was 0.74 (CI, 0.56 to 0.97) and 0.85 (CI, 0.65 to 1.13) after risk factor adjustment.

CONCLUSIONS
The results suggest that the impact of physical activity index on coronary heart disease is mediated through its effects on hypertension, diabetes, cholesterol, and body mass index. These findings support the hypothesis that physical activity is inversely associated with coronary heart disease morbidity and mortality and suggest that physical activity interventions in middle-aged men, by improving cardiovascular risk factor levels, may have significant public health implications in the prevention of coronary heart disease.
Effects of physiological levels of estrogen on coronary vasomotor function in postmenopausal women.
Authors: Gilligan D M , Quyyumi A A , Cannon R O 
Published: June 2012

BACKGROUND
Estrogen replacement therapy has been associated with a reduction in cardiovascular events in postmenopausal women. One of the mechanisms responsible may be a beneficial effect of estrogen on coronary vascular function. We therefore studied the short-term effects of estrogen on coronary artery dimensions and microvascular resistance in postmenopausal women.

METHODS AND RESULTS
Twenty postmenopausal women 61 +/- 7 years old participated in this study. Seven had angiographic evidence of atherosclerosis of the left coronary artery. Coronary artery diameters were measured by quantitative coronary angiography. Blood flow velocity was measured with a Doppler wire placed in a proximal left coronary artery segment. Left coronary artery infusions of acetylcholine (range, 10(-8) to 10(-5) mol/L estimated delivered concentrations) and of adenosine (n = 18) and sodium nitroprusside (n = 10) were performed before and during concomitant continuous intracoronary infusion of 17 beta-estradiol to test endothelium-dependent and independent vasodilation, respectively. Intracoronary infusion of estradiol increased coronary sinus estradiol levels from postmenopausal (16 +/- 11 pg/mL) to premenopausal (282 +/- 121 pg/mL) levels. Estradiol did not affect basal coronary artery diameter, blood flow, or resistance. Epicardial coronary artery constriction induced by acetylcholine infusion in the control study (maximum, 10 +/- 15% from baseline) was prevented during repeat acetylcholine infusion with concomitant estradiol administration (P < .001). Estradiol potentiated the vasodilator coronary microvascular response to acetylcholine as manifest by significantly greater coronary flow (P < .001) and lower coronary resistance (P < .02). The reduction in coronary resistance from baseline in response to acetylcholine was significantly potentiated by estradiol (P = .01), with a mean decrease in coronary vascular resistance during acetylcholine infusion of 20 +/- 38% before and 35 +/- 33% during concomitant estradiol administration. The effect of estradiol on coronary dynamics was similar in women with and women without angiographically apparent left coronary artery atherosclerosis and was most prominent in women with the most impaired responses to acetylcholine at both the epicardial (r = -.72, P < .001) and microvascular (r = -.59, P = .006) coronary artery levels. In contrast, estradiol did not affect the coronary epicardial or microvascular vasodilator responses to adenosine or sodium nitroprusside.

CONCLUSIONS
Physiological levels of 17 beta-estradiol acutely and selectively potentiate endothelium-dependent vasodilation in both large coronary conductance arteries and coronary microvasuclar resistance arteries of postmenopausal women. This effect may contribute to the reduction in cardiovascular events observed with estrogen replacement therapy.
Focal compensatory enlargement of human arteries in response to progressive atherosclerosis. In vivo documentation using intravascular ultrasound.
Authors: Losordo D W , Rosenfield K , Kaufman J , Pieczek A , Isner J M 
Published: June 2012

BACKGROUND
Previous postmortem studies have demonstrated compensatory enlargement of atherosclerotic arteries in animal models and patients. Conclusions regarding these changes were drawn based on a comparison of the dimensions of diseased arteries in one group of subjects with the dimensions of normal arteries in another group. This method admits potential confounding variables, such as demographics and other disease states, which might also have an impact on arterial size.

METHODS AND RESULTS
Using intravascular ultrasound, we studied a total of 62 paired, adjacent normal and diseased sites in the superficial femoral arteries of 20 patients undergoing peripheral vascular interventions. Morphological assessment was performed using a computer-based image analysis system. Measurements were made of the cross-sectional area of the arterial lumen, the atherosclerotic plaque, and the outer border of the artery. These dimensions were then compared to determine the effects of progressive atherosclerosis on arterial morphology. Luminal cross-sectional area decreased from 21.1 +/- 2.2 mm2 in normal segments to 16.7 +/- 0.8 mm2 (P = .0001) in adjacent atherosclerotic segments. Similarly, minimal luminal diameter decreased from 5.7 +/- 0.2 to 5.0 +/- 0.1 mm2, and maximal luminal diameter decreased from 6.2 +/- 0.2 to 5.7 +/- 0.2 mm2. At these same sites, total arterial area was 32.9 +/- 1.6 and 37.9 +/- 1.9 mm2 (P = .0001) in normal and diseased segments, respectively. Minimal and maximal arterial diameters demonstrated similar increases (7.3 +/- 0.2 to 7.7 +/- 0.2 mm2 [P = .0015] and 7.6 +/- 0.2 to 8.3 +/- 0.2 mm2 [P = .0001], respectively). Regression analysis disclosed correlation of the cross-sectional area of plaque to the total arterial area (R = .70, P = .0001).

CONCLUSIONS
Human arteries enlarge in response to progressive atherosclerosis. This compensatory mechanism results in an increase in arterial size that is proportionate to the cross-sectional area of plaque that has accumulated in the vessel. Intravascular ultrasound demonstrates that this process is focal compensatory enlargement at discrete sites of atherosclerotic narrowing immediately adjacent to more normal areas in which arterial size is smaller.
Compensatory carotid artery dilatation in early atherosclerosis.
Authors: Steinke W , Els T , Hennerici M 
Published: June 2012

BACKGROUND
From pathological studies of coronary arteries, it has been recognized that progressive plaque development may be compensated for by an increase of the arterial diameter. However, the dynamics of this process have not been investigated, and it is not known whether compensatory dilatation is a general pathomechanism in human arteries.

METHODS AND RESULTS
Using a high-resolution duplex scanner and subsequent three-dimensional plaque reconstruction, we prospectively studied the effect of carotid plaque development on the vascular geometry in 32 patients at 6- to 12-month intervals. Plaque progression in 41% (n = 26) of studies was associated with an increase of the vessel diameter between 0.4 and 1.2 mm in 76% (n = 20). Among 36 unchanged plaque developments, enlargement of the arterial diameter was assessed in only 28% (n = 10) (P < .001).

CONCLUSIONS
Our data suggest that increasing plaque volume is significantly associated with enlargement of carotid artery segments, which compensates for arterial narrowing in early stages of the disease.
Clinical and prognostic significance of detection of enteroviral RNA in the myocardium of patients with myocarditis or dilated cardiomyopathy.
Authors: Why H J , Meany B T , Richardson P J , Olsen E G , Bowles N E , Cunningham L , Freeke C A , Archard L C 
Published: June 2012

BACKGROUND
Enteroviral RNA sequences have been demonstrated in the myocardium of patients with myocarditis or dilated cardiomyopathy from presentation to end-stage disease. The prognosis of heart muscle disease has not previously been evaluated in relation to the detection of enterovirus in myocardial biopsy tissue.

METHODS AND RESULTS
We studied 123 consecutive patients with heart muscle disease prospectively. Multiple endomyocardial biopsy samples taken from all patients during diagnostic cardiac catheterization were classified histologically and were examined for enteroviral RNA by use of an enterovirus group-specific hybridization probe. Three enterovirus-negative patients with cardiac amyloidosis were excluded from subsequent analysis. Enteroviral RNA sequences were detectable in 41 (34%) of the remaining 120 patients (group A), while 79 (66%) had no virus detected (group B). The groups did not differ significantly in age, sex, symptomatic presentation, or hemodynamic characteristics; duration of symptoms was significantly shorter in group A (7.8 +/- 9.6 versus 14.9 +/- 19.0 months, P < .05). At follow-up (mean, 25 months; range, 11 to 50 months), patients from group A had an increased mortality compared with those in group B (25% versus 4%, respectively; P = .02). Mortality was also statistically greater in patients with symptomatic cardiac failure (P = .02), those with elevated left ventricular end-diastolic pressures (P = .03), and those in New York Heart Association functional classes III and IV (P = .05). Multivariate regression analysis, however, showed that only the presence of enterovirus RNA and symptomatic heart failure were of independent prognostic value.

CONCLUSIONS
These data demonstrate that the detection of enterovirus RNA in the myocardium of patients with heart muscle disease at the time of initial investigation is associated with an adverse prognosis and that the presence of enterovirus RNA is an independent predictor of clinical outcome.
Platelet aggregation and HDL cholesterol are predictive of acute coronary events in heart transplant recipients.
Authors: de Lorgeril M , Boissonnat P , Mamelle N , Martin J L , Monjaud I , Guidollet J , Dureau G , Ninet J , Renaud S 
Published: June 2012

BACKGROUND
Sudden death (SD) and acute myocardial infarction (AMI) are the main complications limiting long-term survival after heart transplantation (HT). They are unpredictable and, at present, unpreventable. Platelet aggregation (PA) has recently emerged as a significant prognostic indicator in nontransplanted coronary disease patients. The main purpose of the present study was to evaluate to what extent PA could predict SD and AMI in long-term survivors of HT independently of serum lipid levels.

METHODS AND RESULTS
We studied 207 patients. All received triple immunosuppressive therapy. During follow-up, the incidence of SD and AMI was determined, and the independent role of PA as predictor was evaluated with other usual risk factors by a Cox multivariate regression model. There were 11 SDs and 14 AMIs after an average follow-up of 642 days, giving an average incidence rate of 7.3 events per year per hundred patients. By univariate analysis, the most potent predictors were ADP-induced platelet aggregation (positive association) and total cholesterol (negative association). Age and length of time since transplant were not predictors. By multivariate analysis, only the secondary wave of ADP-induced platelet aggregation (P = .001) and high-density lipoprotein cholesterol (P = .03) were independent predictors. The relative risk of SD or AMI based on a comparison between patients with high (> 36%) or low (< 36%) ADP-induced platelet aggregation was 4.3 (95% confidence interval, 1.9 to 9.5, P = .0001).

CONCLUSIONS
This study provides the first demonstration of an association between increased platelet aggregation and subsequent SD or AMI in HT recipients. It suggests that platelets and thrombosis also are implicated in the pathogenesis of AMI and SD in HT recipients. Identification of a safe and effective antiplatelet therapy should be actively pursued.