bluuebunny/crossref_metadata_2025 huggingface dataset:
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.
Mechanism-specific effects of adenosine on atrial tachycardia.
Authors: Engelstein E D , Lippman N , Stein K M , Lerman B B
Published: June 2012

BACKGROUND

Recent reports suggest that adenosine, in addition to terminating supraventricular tachycardia involving the atrioventricular (AV) node, may have antiarrhythmic effects on atrial tachycardia. The electrophysiological effects of adenosine on supraventricular tissue include shortening of action potential duration in atrial myocytes mediated by the potassium current, IKACh,Ado; shortening of action potential duration and hyperpolarization in sinus node cells; and anti-adrenergic electrophysiological effects resulting from inhibition of adenylyl cyclase. We therefore hypothesized that the response of atrial tachycardia to adenosine would be mechanism specific, with termination of atrial tachycardia due to sinus node reentry or cAMP-mediated triggered activity, transient suppression of automatic atrial tachycardia, and an absence of antiarrhythmic effect on tachycardia due to intraatrial reentry.

METHODS AND RESULTS

Adenosine (mean +/- SD, 143 +/- 54 micrograms/kg IV) was administered to 27 patients (55 +/- 19 years) in atrial tachycardia whose mechanism was confirmed by electrophysiological study. Adenosine terminated sinus node reentrant tachycardia in 6 of 6 patients and terminated atrial tachycardia due to triggered activity in the 1 patient in whom it was identified. Adenosine transiently suppressed automatic atrial tachycardia in 7 of 7 patients and had no effect in 13 patients with intra-atrial reentrant tachycardia, including 8 patients with atrial flutter.

CONCLUSIONS

These findings demonstrate that adenosine's effects on atrial tachycardia are mechanism specific and can be used to differentiate between reentrant tachycardia confined to the region of the sinus node or atria and between nonreentrant atrial tachycardia due to either triggered activity or automaticity.
Usefulness of transesophageal echocardiography for diagnosis of infected transvenous permanent pacemakers.
Authors: Vilacosta I , Sarriá C , San Román J A , Jiménez J , Castillo J A , Iturralde E , Rollán M J , Martínez Elbal L
Published: June 2012

BACKGROUND

Transesophageal echocardiography is superior to transthoracic echocardiography in detecting left-sided valvular vegetations. There are no data on the value of transesophageal echocardiography in the diagnosis of infected transvenous permanent pacemakers.

METHODS AND RESULTS

Transthoracic and transesophageal echocardiography was performed in 10 patients for whom there was clinical suspicion of infected permanent transvenous pacemakers. Transthoracic echocardiography detected pacemaker lead vegetations in 2 patients, whereas transesophageal echocardiography visualized pacemaker lead vegetations in 7 patients. Surgical confirmation was obtained in 6 of these 7 patients. Most patients had more than one pacemaker electrode in place. Local complications at the generator pocket were present in 6 patients. Staphylococcus was the predominant causative organism.

CONCLUSIONS

Transesophageal echocardiography is superior to transthoracic echocardiography in the detection of pacemaker lead vegetations.
Autoimmunity in idiopathic dilated cardiomyopathy. Characterization of antibodies against the beta 1-adrenoceptor with positive chronotropic effect.
Authors: Magnusson Y , Wallukat G , Waagstein F , Hjalmarson A , Hoebeke J
Published: June 2012

BACKGROUND

Autoantibodies against the beta 1-adrenoceptor have been detected in the sera of patients with idiopathic dilated cardiomyopathy (DCM). The mechanisms by which these autoantibodies can alter normal receptor function are investigated, and the results are interpreted in the light of the beneficial effects of beta 1-blockade in some of these patients.

METHODS AND RESULTS

Autoantibodies against the beta 1-adrenoceptor, affinity purified from sera of patients with idiopathic DCM, were analyzed in a functional test system of spontaneously beating neonatal rat heart myocytes. Antibodies from rabbits immunized with peptides derived from the amino acid sequence of this receptor were also analyzed. Autoantibodies, against the second extracellular loop increased the beating frequency of isolated myocytes in a concentration-dependent manner, to approximately 80% of maximal isoproterenol stimulation. Rabbit anti-peptide antibodies against the second extracellular loop increased the beating frequency correspondingly. Autoantibodies and rabbit anti-peptide antibodies against the second extracellular loop were able to immunoprecipitate the unliganded receptor but not the antagonist-occupied receptor. In contrast, rabbit antibodies against the extracellular N-terminal sequence 34-57 of the beta 1-adrenoceptor were able to immunoprecipitate both the unliganded and the antagonist-occupied receptor although with no effect on the beating frequency of myocytes. The positive chronotropic effect of the antibodies was completely neutralized both by the addition of increasing concentrations of the beta 1-selective antagonist bisoprolol and by preincubation with the peptide corresponding to the second extracellular loop. The antibody-induced increase in beating frequency remained unchanged for more than 6 hours. This should be compared with the isoproterenol-stimulated beating frequency, which undergoes desensitization within 60 minutes. Addition of isoproterenol to autoantibody-stimulated myocytes resulted in only a small increase in beating frequency and did not cause desensitization. Antibodies had only a marginal effect on cyclic AMP production of stimulated cardiomyocytes compared with the 10-fold increase obtained after stimulation with isoproterenol.

CONCLUSIONS

The second extracellular loop of the beta 1-adrenoceptor is a specific target for antibodies with stimulatory activity detected in patients with idiopathic DCM. The antibodies have a positive chronotropic effect on isolated rat heart myocytes. Autoantibody stimulation does not cause the normal agonist-induced desensitization phenomena of the effector system. These findings could contribute to our understanding of the pathophysiological mechanisms of the autoantibodies and of the beneficial effect of beta 1-blocking agents in the treatment of patients with idiopathic DCM.
Blockade of platelet membrane glycoprotein Ib receptors delays intracoronary thrombogenesis, enhances thrombolysis, and delays coronary artery reocclusion in dogs.
Authors: Yao S K , Ober J C , Garfinkel L I , Hagay Y , Ezov N , Ferguson J J , Anderson H V , Panet A , Gorecki M , Buja L M
Published: June 2012

Von Willebrand factor and platelet membrane glycoprotein Ib receptors interact to mediate platelet adhesion and thrombogenesis in stenosed and endothelium-injured arteries. We wished to determine whether blocking glycoprotein Ib receptors with a recombinant von Willibrand factor binding domain (VCL) increases the time required for thrombus formation after injury to the coronary arteries. We also wished to determine whether, after thrombolysis with tissue plasminogen activator (TPA), VCL delays or protects against coronary artery reocclusion. Twenty-seven dogs were treated with either saline, VCL, or aspirin before thrombosis was induced in their coronary arteries by electrical injury. The time from injury to the formation of occlusive thrombi was significantly greater with VCL (70 +/- 10 minutes) and aspirin (69 +/- 20 minutes) than with saline (18 +/- 3 minutes, P < .001 and P < .05). Thrombosis was induced in 30 other dogs that then received thrombolytic treatment in four groups. Our major finding was that coronary artery reocclusion occurred in 72 +/- 11 minutes after treatment with TPA (80 micrograms/kg + 8 micrograms.kg-1.min-1) and heparin (200 U/kg) (n = 7); in 142 +/- 24 minutes after TPA, heparin, and VCL (4 mg/kg + 2 mg.kg-1.h-1) (n = 7) (compared with TPA and heparin, P < .05); in 74 +/- 13 minutes after TPA, heparin, and aspirin (5 mg/kg) (n = 8); and in 173 +/- 8 minutes after TPA, heparin, VCL, and aspirin (n = 8) (compared with TPA and heparin, P < .001). Thus, VCL increases the length of time required for thrombus formation in coronary arteries, and, when given with TPA and heparin, delays coronary artery reocclusion more effectively than aspirin.
Abnormalities of cardiac sympathetic function in pacing-induced heart failure as assessed by [123I]metaiodobenzylguanidine scintigraphy.
Authors: Simmons W W , Freeman M R , Grima E A , Hsia T W , Armstrong P W
Published: June 2012

BACKGROUND

Increased activity of the sympathetic nervous system contributes significantly to the pathophysiology of heart failure. However, cardiac efferent sympathetic function has not been well characterized in this disorder. In this study, we evaluated cardiac sympathetic innervation using [123I]metaiodobenzylguanidine (MIBG) and compared this with left ventricular (LV) tissue norepinephrine concentration and myocardial perfusion, assessed by 201Tl, in a canine model of heart failure.

METHODS AND RESULTS

Planar and tomographic cardiac imaging was performed for MIBG and 201Tl in 23 dogs: 8 normal dogs (group 1) and 15 dogs with heart failure induced by right ventricular pacing at 250 beats per minute either continuously for 3 weeks (group 2) or intermittently for 7 weeks (group 3). Plasma and LV tissue norepinephrine concentrations were also measured. Scintigraphic studies in group 2 demonstrated reduced cardiac MIBG activity at heart failure (0.17 +/- 0.04 versus 0.29 +/- 0.05 counts per megabecquerel per pixel at baseline, mean +/- SD; P = .0001), whereas thallium activity was unchanged from baseline. This reduction in cardiac MIBG activity with heart failure was associated with increased intraimage variability in the distribution of MIBG activity (21 +/- 8% versus 13 +/- 7% at baseline, mean +/- SD; P = .0001). The MIBG heart-to-lung ratio was calculated for all groups to control for the inhibitory effect that plasma norepinephrine has on the neuronal uptake of MIBG. There was a positive correlation between LV tissue norepinephrine and the MIBG heart-to-lung ratio (r = .67; P < .001; n = 22), for which the group 2 heart failure animals had the lowest values. No relation existed between plasma norepinephrine concentration and the MIBG heart-to-lung ratio. In addition, regional LV tissue norepinephrine concentration and MIBG activity were both lowest at the apex in normal (group 1) and heart failure (group 2) dogs. The MIBG heart-to-lung ratio also correlated inversely with cardiac filling pressure (r = -.59; P < .05) and heart rate (r = -.65; P < .01) and positively with cardiac output (r = .53; P < .05).

CONCLUSIONS

Heart failure is associated with severe cardiac adrenergic dysfunction manifested by reduced MIBG activity and increased heterogeneity in the LV distribution of MIBG. Furthermore, MIBG scintigraphy is a simple noninvasive method for assessing global and regional LV tissue norepinephrine levels.
First use of an untethered, vented electric left ventricular assist device for long-term support.
Authors: Frazier O H
Published: June 2012

This report describes the first long-term (505-day) application of the vented electric (VE) HeartMate left ventricular assist device (LVAD) (Thermo Cardiosystems, Inc). The device consists of an abdominally placed, battery-powered titanium blood pump that, in contrast to earlier pneumatically powered systems, allows patients untethered freedom of movement. The batteries last 5 to 8 hours and can be changed on a rotating basis indefinitely. The patient, a 33-year-old man (90 kg, blood type O) with idiopathic cardiomyopathy, experienced end-organ heart failure (New York Heart Association [NYHA] class IV) while he was awaiting heart transplantation. When his hemodynamic criteria met those outlined in the protocol, we implanted the VE-LVAD as a bridge to transplantation. The patient was supported by the device for more than 16 months. His cardiac status returned to NYHA class I, and he was eventually allowed to take day trips outside the hospital as he awaited transplantation. The VE-LVAD enabled the patient to participate in activities such as eating in restaurants, going to movies, and practicing basketball shots. Unfortunately, the patient died suddenly due to a neurological thromboembolic event that occurred on day 503 of VE-LVAD support. The VE-LVAD improved native left ventricular function by chronic unloading, and ventricular remodeling resulted in a more normal configuration anatomically, physiologically, and ultimately, histologically and pathologically.
Pathophysiological correlates of increased serum tumor necrosis factor in patients with congestive heart failure. Relation to nitric oxide-dependent vasodilation in the forearm circulation.
Authors: Katz S D , Rao R , Berman J W , Schwarz M , Demopoulos L , Bijou R , LeJemtel T H
Published: June 2012

BACKGROUND

Tumor necrosis factor-alpha (TNF alpha), which we and others have shown to be elevated in patients with severe congestive heart failure (CHF), is involved in the regulation of nitric oxide metabolism. Whether increased concentrations of TNF alpha affect nitric oxide-mediated vasodilation in patients with CHF has not been studied previously.

METHODS AND RESULTS

Serum concentrations of TNF alpha, interleukin-1 (IL-1), interleukin-2 (IL-2), and interleukin-6 (IL-6) were determined in venous blood (pg/mL) from 17 patients with stable New York Heart Association classes II and III CHF (mean age, 58 +/- 11 years; mean left ventricular ejection fraction, 19.5 +/- 7.3) and 17 age-matched normal subjects with enzyme-linked immunosorbent assays (detection limit of assays, 20 pg/mL). Forearm blood flows were determined with plethysmography (mL/min per 100 mL) in 17 patients and 7 normal subjects in response to brachial artery administration of graded concentrations of acetylcholine (10(-6) mol/L and 10(-5) mol/L) and nitroglycerin (10(-7) mol/L and 10(-6) mol/L). Serum concentrations of TNF alpha were above the detection limits of the assay in 10 of 17 patients with CHF (mean serum concentration, 39.4 +/- 3.8 pg/mL). Forearm blood flow responses to acetylcholine and nitroglycerin were significantly greater in these 10 patients than in the 7 patients without detectable serum TNF alpha and were closely correlated with TNF alpha serum concentrations (r > or = .81, P < .01 and r > or = .65, P < .05 respectively). In 1 of 17 normal subjects, the serum concentration of TNF alpha was just above the detection limit of the assay. Serum concentrations of IL-2 were above the detection limit of the assay in 14 of 17 patients with CHF (mean serum concentration, 112 +/- 19 pg/mL). IL-2 was not detected in the serum of normal subjects. Serum concentrations of IL-1 and IL-6 were below the detection limit of the assays in all patients and normal subjects assayed.

CONCLUSIONS

Increased TNF alpha concentrations are closely correlated with forearm blood flow responses to regional administration of acetylcholine and nitroglycerin. The significant correlation between serum concentrations of TNF alpha and forearm blood flow responses to acetylcholine and nitroglycerin suggests that both the inducible and the constitutive forms of nitric oxide synthase are involved in the regulation of peripheral vasomotor tone in patients with CHF.
Circadian rhythms of frequency domain measures of heart rate variability in healthy subjects and patients with coronary artery disease. Effects of arousal and upright posture.
Authors: Huikuri H V , Niemelä M J , Ojala S , Rantala A , Ikäheimo M J , Airaksinen K E
Published: June 2012

BACKGROUND

Altered neural regulation of the cardiovascular system may be an important factor for various manifestations of ischemic heart disease. This research was designed to compare the circadian rhythm of cardiac neural regulation and autonomic responses to arousal and upright posture between patients with uncomplicated coronary artery disease (CAD) and age-matched subjects with no evidence of heart disease.

METHODS AND RESULTS

Twenty-four-hour heart rate variability (HRV) in the frequency domain was analyzed in 20 male patients (mean age, 52 +/- 7 years) with angiographic evidence of CAD without prior myocardial infarction and in 20 healthy men (mean age, 51 +/- 8 years) with no clinical, echocardiographic, or exercise ECG evidence of heart disease. None of the 24-hour average frequency-domain components of HRV differed significantly between the two groups. Healthy subjects had a significant circadian rhythm of normalized units of high-frequency (HF) power of HRV with higher values during sleep. Normalized units of low-frequency (LF) power and the LF/HF ratio also showed a significant circadian rhythm in healthy subjects, with higher values during the daytime. No significant circadian rhythms in any of the normalized spectral components of HRV were observed in patients with CAD, and the night-day difference in LF/HF ratio was smaller in the patients with CAD than in the healthy subjects (0.5 +/- 1.4 versus 1.8 +/- 0.7, P < .001). Awakening when in the supine position resulted in a significant increase in the LF/HF ratio (P < .01) in the healthy subjects, but no significant changes in HRV were observed after awakening in patients with CAD. Assumption of upright position resulted in a comparable decrease in the components of HRV between the groups.

CONCLUSIONS

The circadian rhythm of cardiac neural regulation is altered in patients with uncomplicated CAD. Reduced autonomic responses to sleep-wake rhythm suggest that the modulation of cardiac autonomic function by stimuli from the central nervous system is impaired in CAD.
Six-month clinical and angiographic follow-up after direct angioplasty for acute myocardial infarction. Final results from the Primary Angioplasty Registry.
Authors: Brodie B R , Grines C L , Ivanhoe R , Knopf W , Taylor G , O'Keefe J , Weintraub R A , Berdan L G , Tcheng J E , Woodlief L H
Published: June 2012

BACKGROUND

After direct angioplasty in the setting of acute myocardial infarction, patients were followed clinically and angiographically for 6 months at six experienced centers to evaluate outcomes.

METHODS AND RESULTS

Of 258 patients with 6-month follow-up after surviving initial hospitalization, 5 (2%) died, 8 (3%) had nonfatal infarctions, 56 (22%) had chest pain, of whom 25 (10%) required hospitalization, and 42 (16%) patients needed repeat angioplasty. Of 203 eligible patients, 154 (76%) had angiographic follow-up. The infarct-related artery remained patent (defined as TIMI 2 or 3 flow) in 87%, while 13% developed reocclusion (TIMI 0 or 1 flow) by 6 months after discharge. Patients with reocclusion were more likely to have adverse events, including 35% with clinically evident reinfarction and 59% requiring repeat angioplasty. The median ejection fraction improvement from acute to follow-up study was 6%, with no improvement in patients with a reoccluded infarct-related artery and an 8% improvement in patients with a patent infarct-related artery.

CONCLUSIONS

The positive clinical outcomes recorded immediately after direct angioplasty persisted through 6 months of follow-up. Although the incidence of clinical end points was equivalent to or lower than thrombolytic therapy trials, restenosis is a substantial problem. These findings provide evidence beyond the initial hospitalization that direct angioplasty is a reasonable choice for the treatment of acute myocardial infarction.
Optimal blood pressure control in treated hypertensive patients. Report from the Department of Health Hypertension Care Computing Project (DHCCP).
Authors: Bulpitt C J , Palmer A J , Fletcher A E , Beevers D G , Coles E C , Ledingham J G , O'Riordan P W , Petrie J C , Rajagopalan B E , Webster J
Published: June 2012

BACKGROUND

We wished to determine the range of treated systolic (SBP) and diastolic blood pressure (DBP) associated with the best survival in hypertensive patients.

METHODS AND RESULTS

We conducted a cohort study of patients enrolled in the DoH Hypertension Care Computer Project. Five specialist hypertension clinics (95% of patients) and general practitioners (5%) followed 6214 patients (3070 men and 3144 women) with an average age of 52 years for a mean of 107 months. Total, cardiovascular, ischemic heart disease, (IHD) and stroke mortality were the outcome measures. Age-adjusted relative hazard rates were calculated giving the effect on mortality of systolic or diastolic pressure being higher by 1 mm Hg. In men the optimal level of SBP for all four measures of mortality was the lowest pressure range observed, 92 to 133 mm Hg (median 127). For women the treated SBP range of 96 to 148 mm Hg (median 137) was associated with a low total mortality and also with low to moderate rates for IHD and stroke mortality. Relative hazard rates (P < .001) for IHD mortality were 1.010 for men and 1.013 for women and for stroke mortality were 1.018 and 1.021, respectively. The results were similar in men under and over the age of 60. SBP and DBP tended to be more important in younger than older women. For treated DBP in men, a pressure of 55 to 94 mm Hg (median 87) was associated with a low total mortality. The lowest stroke mortality in men was observed for a DBP range of 55 to 83 mm Hg (median 80) but with a tendency for an increase in IHD mortality. For women DBP < 95 mm Hg (range 55 to 94, median 87) also was associated with a low total mortality. IHD mortality in women was not closely related to treated DBP, relative hazard rate = 1.003, [95% confidence index (CI); 0.990,1.017] but the relative hazard rate for men was 1.011, (95% CI; 1.000, 1.022). The relative hazard rates for treated DBP and stroke were high at 1.035 and 1.028 for men and women, respectively (P < .001). IHD mortality increased in the one third of patients with the greatest fall in DBP on treatment, provided they were not initially in the one-third group with highest untreated DBP.

CONCLUSIONS

The best overall survival was associated with a treated SBP of < 134 mm Hg in men and < 149 mm Hg in women and a treated DBP of < 95 mm Hg.
Mechanisms responsible for sympathetic activation by cigarette smoking in humans.
Authors: Grassi G , Seravalle G , Calhoun D A , Bolla G B , Giannattasio C , Marabini M , Del Bo A , Mancia G
Published: June 2012

BACKGROUND

The pressor and tachycardic effects of cigarette smoking are associated with an increase in plasma catecholamines, suggesting the dependence of these effects on adrenergic stimulation. Whether the stimulation occurs at a central or a peripheral level and whether reflex mechanisms are involved is unknown.

METHODS AND RESULTS

In nine normotensive healthy subjects (age, 33.0 +/- 3.5 years, mean +/- SEM), we measured blood pressure (Finapres device), heart rate (ECG), calf blood flow and vascular resistance (venous occlusion plethysmography), plasma norepinephrine and epinephrine (high-performance liquid chromatography assay), and postganglionic muscle sympathetic nerve activity (microneurography from the peroneal nerve) while subjects were smoking a filter cigarette (nicotine content, 1.1 mg) or were in control condition. Cigarette smoking (which raised plasma nicotine measured by high-performance liquid chromatography from 1.0 +/- 0.9 to 44.2 +/- 7.1 ng/mL) markedly and significantly increased mean arterial pressure (+13.2 +/- 2.3%), heart rate (+30.3 +/- 4.7%), calf vascular resistance (+12.1 +/- 4.9%), plasma norepinephrine (+34.8 +/- 7.0%), and plasma epinephrine (+90.5 +/- 39.0%). In contrast, muscle sympathetic nerve activity showed a marked reduction (integrated activity -31.8 +/- 5.1%, P < .01). The reduction was inversely related to the increase in mean arterial pressure (r = -.67, P < .05), but the slope of the relation was markedly less (-54.1 +/- 7.5%, P < .05) than that obtained by intravenous infusion of phenylephrine in absence of smoking. The hemodynamic and neurohumoral changes were still visible 30 minutes after smoking and occurred again on smoking a second cigarette. Sham smoking was devoid of any hemodynamic and neurohumoral effect.

CONCLUSIONS

These data support the hypothesis that in humans the sympathetic activation induced by smoking depends on an increased release and/or a reduced clearance of catecholamines at the neuroeffector junctions. Central sympathetic activity is inhibited by smoking, presumably via a baroreceptor stimulation triggered by the smoking-related pressor response. The baroreflex is impaired by smoking, however, indicating that partial inability to reflexly counteract the effect of sympathetic activation is also responsible for the pressor response.
Diminished vascular response to inhibition of endothelium-derived nitric oxide and enhanced vasoconstriction to exogenously administered endothelin-1 in clinically healthy smokers.
Authors: Kiowski W , Linder L , Stoschitzky K , Pfisterer M , Burckhardt D , Burkart F , Bühler F R
Published: June 2012

BACKGROUND

Smoking is a major risk factor for the development of atherosclerosis. Because endothelial dysfunction may be a marker for future atherosclerosis, we investigated the effects of smoking on endothelium-dependent control of vascular tone.

METHODS AND RESULTS

The effects of brachial arterial infusions of NG-monomethyl-L-arginine (L-NMMA), a nitric oxide synthesis inhibitor; sodium nitroprusside; endothelin-1; and norepinephrine on forearm blood flow (strain-gauge plethysmography) were compared in 29 long-term smokers and 16 nonsmokers. The acute effects of smoking on systemic hemodynamics, plasma catecholamines, and forearm vascular responses to these compounds were investigated in smokers only. Smokers did not differ from nonsmokers (n = 16) regarding the vascular effects of sodium nitroprusside (n = 13) or vasoconstriction due to norepinephrine and endothelin-1 (n = 16). Low-dose endothelin-1-induced vasodilation, believed to reflect endothelial prostacyclin or nitric oxide release, was absent in smokers (n = 16), and their increase of forearm vascular resistance (FVR) after L-NMMA (n = 13) was impaired (35.6 +/- 27.9% versus 118.8 +/- 43.2%, P < .001). Short-term smoking (n = 11) increased blood pressure, heart rate, and plasma epinephrine concentrations (P < .05 or less); enhanced endothelin-1-induced vasoconstriction (delta FVR, 457 +/- 192% versus 254 +/- 143%, P < .01); and decreased norepinephrine-induced vasoconstriction (P < .05), but had no effect on the other interventions.

CONCLUSIONS

Long-term smoking is associated with a diminished nitric oxide-dependent component of basal vascular tone and an impaired endothelium-dependent vasodilator response to low-dose endothelin-1 and short-term smoking enhances endothelin-1-induced vasoconstriction. Impaired endothelial control of vascular tone might reflect impairment of normal antiatherosclerotic endothelial functions in smokers, but the relevance of smoking-induced enhancement of endothelin-1 vasoconstriction remains to be determined.
Mechanism of efficacy of 2-amino oleic acid for inhibition of calcification of glutaraldehyde-pretreated porcine bioprosthetic heart valves.
Authors: Chen W , Schoen F J , Levy R J
Published: June 2012

BACKGROUND

Calcification is a frequent cause of the clinical failures of glutaraldehyde-pretreated bioprosthetic heart valves (BPHV) fabricated from glutaraldehyde-cross-linked porcine aortic valves. 2-Amino oleic acid (AOA) has been shown in previous in vivo studies to be a promising anticalcification agent. Our objective was to investigate the mechanism of calcification inhibition mediated by AOA pretreatment of porcine aortic valve bioprostheses.

METHODS AND RESULTS

BPHV tissues were treated with an AOA solution for 72 hours before experimentation. The diffusion of AOA across both cusp and aortic wall was evaluated. The lag time for AOA to diffuse across the aortic wall was prolonged compared with that of the cusp. An extraction study was performed to determine the stability of AOA binding; the results indicated that the binding was relatively stable regardless of solvent extraction conditions. The interaction between ionic calcium and AOA on treated tissue also was investigated by evaluating the patterns of calcium diffusion across both treated and untreated tissues. The results showed that AOA significantly reduced the diffusion of calcium. AOA inhibition of aortic valve calcification (calcium level, 5.5 +/- 3.0 mg/g of tissue compared with control; calcium level, 91.2 +/- 19.5 mg/g of tissue) but not aortic wall (calcium level, 158.7 +/- 10.3 mg/g of tissue compared with control; calcium level, 157.5 +/- 7.9 mg/g of tissue) was demonstrated on representative specimens from valves implanted in left ventricular apicoaortic shunts explanted after 150 days.

CONCLUSIONS

AOA covalently binds to glutaraldehyde-pretreated bioprosthetic heart valve tissue, presumably as the result of an aldehyde-amino reaction. Covalently bound AOA diminishes Ca2+ diffusion compared with non-AOA-pretreated bioprosthetic tissues. This may explain in part the anticalcification mechanism of AOA. Furthermore, AOA inhibits calcification of porcine BPHV cusps in the circulation.
Acute and follow-up intravascular ultrasound findings after balloon dilation of coarctation of the aorta.
Authors: Sohn S , Rothman A , Shiota T , Luk G , Tong A , Swensson R E , Sahn D J
Published: June 2012

BACKGROUND

The study objective was to examine the vascular wall changes caused by balloon dilation of coarctation of the aorta (CoA) acutely and at short-term follow-up using intravascular ultrasound imaging. Intravascular ultrasound has been valuable in assessing the vessel wall changes in coronary and peripheral arteries after balloon dilation, often with more detail than angiography.

METHODS AND RESULTS

Intravascular ultrasound imaging, using 4.8F, 20-MHz or 6.2F, 12.5-MHz catheters on either Diasonics or HP scanners, was performed in 17 patients during balloon angioplasty for native (n = 12) and recurrent (n = 5) CoAs. Nine patients were also studied at the time of follow-up cardiac catheterization 28.1 +/- 18.0 months after angioplasty. Immediately after dilation, the mean pressure gradient across the CoA decreased from 42.9 +/- 16.4 to 9.0 +/- 5.4 mm Hg (P < .001) and the mean diameter of the coarcted segment increased from 4.4 +/- 1.9 to 7.9 +/- 2.4 mm (P < .001). An intimal tear or flap was noted by ultrasound in 12 of the 12 native CoAs and 4 of the 5 recoarctations. In contrast, only 6 of the native CoAs and 2 of the recoarctations had an intimal flap or dissection detected by angiography. At follow-up, the residual pressure gradient did not significantly change from that measured immediately after dilation, but the CoA diameter increased from 7.8 +/- 1.5 to 9.9 +/- 2.3 mm (P < .01). No aneurysms were detected. Four of the 9 patients showed ultrasonic and angiographic evidence of healing and remodeling with diminution in size or disappearance of the intimal tears.

CONCLUSIONS

There is a high incidence of intimal tears and dissections immediately after balloon angioplasty for native and recurrent CoAs. Intravascular ultrasound is more sensitive than angiography in detecting the vascular wall changes. Even significant intimal tears are not necessarily associated with aneurysm formation, and many decrease in size or disappear at short-term follow-up.