bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vasodilatory effects of C-type natriuretic peptide on forearm resistance vessels are distinct from those of atrial natriuretic peptide in chronic heart failure.
Authors: Nakamura M , Arakawa N , Yoshida H , Makita S , Hiramori K 
Published: June 2012

BACKGROUND
C-type natriuretic peptide (CNP) is a newly identified peptide that is structurally related to atrial natriuretic peptide (ANP). Although it has been suggested that CNP is released from the endothelium for the regulation of local vascular tone, no data are available concerning the vasodilatory response to CNP in humans.

METHODS AND RESULTS
Strain-gauge plethysmography was used to determine the vasodilatory effects of intra-arterially infused CNP compared with the effects of ANP infusion in 11 patients with chronic heart failure (CHF) and 11 age-matched healthy controls. Graded doses of CNP and ANP (8, 16, 32, and 48 pmol.min-1.dL-1 tissue volume) were administered randomly into the nondominant brachial artery, and forearm blood flow (FBF) was measured. No significant changes in systemic blood pressure and heart rate were found during the study. Both the absolute and percent FBF responses to ANP relative to the baseline value were significantly lower in CHF patients than in healthy controls (P < .01), whereas the responses to CNP were similar. The calculated forearm spillover of cyclic GMP (cGMP) was significantly lower in CHF patients receiving the highest dose of ANP (P < .02), whereas changes in cGMP spillover after the equimolar dose of CNP were significantly higher (P < .02), despite the lesser potency of CNP.

CONCLUSIONS
In patients with CHF the peripheral vasodilatory effect of ANP is attenuated, but CNP-induced peripheral vasorelaxation is preserved, with CNP being less potent for equimolar doses.
Activation of angiotensinogen and angiotensin-converting enzyme gene expression in the left ventricle of senescent rats.
Authors: Heymes C , Swynghedauw B , Chevalier B 
Published: June 2012

BACKGROUND
During senescence, the plasma angiotensin II concentration is decreased, but the regulation of intracardiac angiotensin II synthesis has never been investigated. The purpose of this work was to determine the cardiac content of both angiotensinogen (ANG) and angiotensin-converting enzyme (ACE) mRNAs in 24-month-old Wistar rats.

METHODS AND RESULTS
Total cardiac RNAs and known amounts of ANG and ACE mRNA transcripts, used as standards, were hybridized on slot blots with specific cDNA probes. The quantities of ANG and ACE mRNA were evaluated from the regression lines obtained with fragments of ANG and ACE mRNA in vitro transcripts. With aging, while the overall plasma renin-angiotensin system (RAS) activity decreased, in the left ventricle (LV) the amounts of ANG and ACE mRNAs were increased by fivefold (P < .01) and 2.5-fold (P < .01), respectively, compared with young adult controls. By contrast, in the right ventricle (RV) the same mRNA levels remained unchanged. In parallel, we also found an enhanced expression of the atrial natriuretic factor (ANF) in the LV but not in the RV.

CONCLUSIONS
During senescence, the depressed circulating RAS activity is in contrast to the increase of both ANG and ACE mRNA levels in the LV. Such an upregulation in both gene activities is more likely to be related to the age-associated changes in arterial compliance rather than to hormonal changes, since (1) this regulation is found only in the LV and (2) the same pattern of regulation is also observed for the ANF mRNA level.
A prospective investigation of elevated lipoprotein (a) detected by electrophoresis and cardiovascular disease in women. The Framingham Heart Study.
Authors: Bostom A G , Gagnon D R , Cupples L A , Wilson P W , Jenner J L , Ordovas J M , Schaefer E J , Castelli W P 
Published: June 2012

BACKGROUND
Sinking prebeta lipoprotein is a putative marker for elevated levels of lipoprotein (a). Although prospective data suggest that increased plasma lipoprotein (a) is an independent risk factor for coronary heart disease in men, no prospective studies are available in women.

METHODS AND RESULTS
From 1968 through 1975, sinking prebeta lipoprotein was determined by paper electrophoresis in 3103 women Framingham Heart Study participants who were free of prevalent cardiovascular disease. A sinking prebeta lipoprotein band was detectable in 434 of the women (14%) studied. The median follow-up interval was approximately 12 years. Incident cardiovascular disease was associated with band presence using a proportional hazards model that included age, smoking, body mass index, systolic blood pressure, glucose intolerance, low- and high-density lipoprotein cholesterol, and ECG left ventricular hypertrophy. Multivariable adjusted relative risk estimates (with 95% confidence intervals) for outcomes in the band present versus absent groups were as follows: myocardial infarction (82 events), 2.37 (1.48 to 3.81); intermittent claudication (62 events), 1.94 (1.07 to 3.50); cerebrovascular disease (83 events), 1.88 (1.12 to 3.15); total coronary heart disease (174 events), 1.61 (1.13 to 2.29); and total cardiovascular disease (305 events), 1.44 (1.09 to 1.91). A subset analysis indicated that band presence was 50.9% sensitive and 95.4% specific for detecting plasma lipoprotein (a) levels of > 30 mg/dL, the threshold value linked to increased cardiovascular disease risk in men.

CONCLUSIONS
Sinking prebeta lipoprotein was a valid surrogate for elevated lipoprotein (a) levels in Framingham Heart Study women. Band presence and, equivalently, elevated plasma lipoprotein (a), was a strong, independent predictor of myocardial infarction, intermittent claudication, and cerebrovascular disease. Confirmation of these findings in other longitudinal studies of women is needed.
Transcatheter ablation of posteroseptal accessory pathways using a venous approach and radiofrequency energy.
Authors: Dhala A A , Deshpande S S , Bremner S , Hempe S , Sra J S , Blanck Z , Akhtar M , Jazayeri M R 
Published: June 2012

BACKGROUND
The efficacy of transcatheter ablation of atrioventricular (AV) accessory pathways (APs) located in the posteroseptal region using a right atrial approach and radiofrequency energy was evaluated.

METHODS AND RESULTS
Fifty consecutive patients with APs in the posteroseptal region underwent radiofrequency catheter ablation. Manifest preexcitation was present in 36 patients and a concealed AP in 14. In 18 patients (group 1), the ventriculoatrial (VA) interval during orthodromic tachycardia was prolonged by 21 +/- 7 milliseconds (range, 10 to 30 milliseconds) with functional left bundle-branch block. In 16 patients (group 2), functional left bundle-branch block caused no VA interval prolongation. The remaining 16 patients (group 3) had no inducible left bundle-branch block during orthodromic tachycardia. Functional right bundle-branch block was induced in 30 patients with no effect on the VA interval. In group 1, of 14 patients with manifest preexcitation during sinus rhythm, 10 patients had a positive delta wave in lead V1. Of 10 group 2 patients with manifest preexcitation, only 5 had a positive delta wave in lead V1. In group 3, of 12 patients with manifest preexcitation, 7 exhibited a positive delta wave in lead V1. All posteroseptal APs were successfully ablated, and this was achieved via a right atrial approach in 48 patients and left ventricular approach in only 2. Successful sites were at the posteroseptal region of the tricuspid annulus (30 patients), within the terminal 1 cm of the coronary sinus including its ostium (16 patients), and at the inferomedial aspect of the right atrium posterior to the coronary sinus ostium (2 patients). The posteroseptal region of the left ventricle was the site of successful ablation in 2 patients. Six patients with a recurrence of AP conduction required a repeat ablation, with successful results in 5. Thirty-five patients had a complete electrophysiological evaluation 2 to 3 months after their successful ablation and were found to have no functioning AP. In 49 patients with a final successful ablation, no recurrence of symptoms was noted during a mean follow-up period of 12 +/- 9 months. Complications occurring in 3 patients were cardiac tamponade requiring surgical drainage and repair of a right ventricular tear, pericardial effusion with no hemodynamic consequence that spontaneously resolved, and a transient 2:1 atrioventricular block.

CONCLUSIONS
These data suggest that posteroseptal APs are amenable to successful ablation using a right atrial approach. Success was achieved in 47 cases (94%) in this series even though the ECG and/or electrophysiological characteristics of the posteroseptal APs of some patients were suggestive of "left-sided" pathways.
Power spectrum analysis of heart rate variability to assess the changes in sympathovagal balance during graded orthostatic tilt.
Authors: Montano N , Ruscone T G , Porta A , Lombardi F , Pagani M , Malliani A 
Published: June 2012

BACKGROUND
The powers of the low-frequency (LF) and high-frequency (HF) oscillations characterizing heart rate variability (HRV) appear to reflect, in their reciprocal relationship, changes in the state of the sympathovagal balance occurring during numerous physiological and pathophysiological conditions. However, no adequate information is available on the quantitative resolution of this methodology.

METHODS AND RESULTS
We studied 22 healthy volunteers (median age, 46.5 years) who were subjected after a rest period to a series of passive head-up tilt steps randomly chosen from the following angles: 15 degrees, 30 degrees, 45 degrees, 60 degrees, and 90 degrees. From the continuous ECG, after appropriate analog-to-digital conversion, a personal computer was used to compute, with an autoregressive methodology, time and frequency domain indexes of RR interval variability. Spectral and cross-spectral analysis with the simultaneously recorded respiratory signal excluded its contribution to LF. Age was significantly correlated to variance and to the absolute values in milliseconds squared of very-low-frequency (VLF), LF, and HF components. The tilt angle was correlated to both LF and HF (expressed in normalized units [nu]) and to the LF-to-HF ratio (r = .78, -.72, and .68; respectively). Lower levels of correlation were found with HF (in ms2) and RR interval. No correlation was present between tilt angle and variance, VLF, or LF (in ms2). Individual analysis confirmed that the use of nu provided the greatest consistency of results.

CONCLUSIONS
Spectral analysis of HRV, using nu or LF-to-HF ratio, appears to be capable of providing a noninvasive quantitative evaluation of graded changes in the state of the sympathovagal balance.
Rate-dependent properties of adenosine-induced negative dromotropism in humans.
Authors: Lai W T , Lee C S , Wu S N 
Published: June 2012

BACKGROUND
The antiarrhythmic effects of sodium channel and calcium channel blockers are known to be rate dependent. Little is known about the rate-dependent effect of adenosine on human atrioventricular (AV) nodal conduction. The purpose of this study was to determine whether the negative dromotropic effect of adenosine is dependent on heart rate.

METHODS AND RESULTS
Atrial pacing at 20-millisecond increments decreasing stepwise was performed, and the curves that relate the AH interval to the atrial pacing cycle length were analyzed. The change in AV nodal function was evaluated in three protocols: (1) In 8 group 1A and 6 group 1B patients, an intravenous infusion of adenosine at a dose of 140 and 320 micrograms.kg-1.min-1 was given, respectively; (2) a bolus injection of a fixed dose of adenosine was given to 12 group 2A patients without and 6 group 2B patients with propranolol (0.1 mg/kg) treatment; and (3) in 12 group 3 patients, the AV nodal function was evaluated after intravenous propranolol (0.05 mg/kg) and after subsequent intravenous aminophylline (loading dose, 5 mg/kg; maintenance dose, 0.9 mg.kg-1.h-1). No significant depression of AV nodal function could be demonstrated during intravenous infusion of adenosine. The bolus injection of adenosine could prolong the AH interval, which was dependent on heart rate and more significant at a shorter pacing cycle length. Intravenous propranolol significantly depressed the AV nodal conduction and shifted the curves of the AH interval versus the pacing cycle length to the right. Subsequent intravenous aminophylline shortened the AV nodal conduction time, however, in a rate-independent manner.

CONCLUSIONS
The negative dromotropic effects induced by intravenous bolus injection of adenosine became more pronounced at fast atrial pacing rates. These results indicate that adenosine causes rate-dependent prolongation of AV nodal conduction in humans.
Mitogenic effect of serotonin on vascular endothelial cells.
Authors: Pakala R , Willerson J T , Benedict C R 
Published: June 2012

BACKGROUND
Recent studies indicate that serotonin (5-HT) has a growth-promoting effect on several different cell types, including smooth muscle cells. After percutaneous transluminal coronary angioplasty, there is damage and denudation of vascular endothelial cells, which promotes platelet aggregation at the site of injury. Aggregating platelets release 5-HT; thus, a high concentration of the amine may be present at sites of endothelial damage, which may act as a mitogen to endothelial cells.

METHODS AND RESULTS
The mitogenic effect of 5-HT was examined on canine and bovine aortic endothelial cells by (1) assessing the increase in [3H]thymidine incorporation into DNA and (2) assessing the increase in the absolute number of cells after stimulation with 5-HT. 5-HT at an added concentration of 200 to 1000 mumol/L in the media induced a significant increase in [3H]thymidine incorporation into endothelial cells and an increase in cell number. This effect was not observed with fibroblasts. As the concentrations of added 5-HT were decreased, the endothelial cells had to be stimulated with 5-HT for longer periods to induce the same degree of cellular proliferation. The precursors and metabolic breakdown products of 5-HT were inactive. The 5-HT-induced endothelial proliferation was reversed by 5-HT2 receptor antagonists and pertussis toxin. These data suggest that the mitogenic effect of 5-HT on endothelial cells is mediated by the 5-HT2 receptor, which is coupled to a G protein.

CONCLUSIONS
5-HT is a mitogen for endothelial cells at concentrations likely to be present at sites of vascular injury. This effect is probably mediated via the 5-HT2 receptor. The growth-promoting effects of 5-HT on endothelial cells may facilitate the healing of intima after vascular damage.
Modulation of expression of monocyte/macrophage plasminogen activator activity and its implications for attenuation of vasculopathy.
Authors: Lundgren C H , Sawa H , Sobel B E , Fujii S 
Published: June 2012

BACKGROUND
The binding of urokinase-type plasminogen activator (uPA) to its receptor (uPAR) on cell surfaces has the potential to influence degradation of extracellular matrix (ECM). Thus, uPA bound to monocyte/macrophages and its interactions with plasminogen activator inhibitors types 1 and 2 (PAI-1 and PAI-2) may modify atherogenesis by altering cell-associated proteolytic activity, degradation of ECM, and neointimal formation at sites of vascular injury.

METHODS AND RESULTS
To determine whether the expression of proteins on the surface of cells involved in fibrinolysis changes in human cells in response to mediators implicated in atherogenesis, we exposed U937 cells (an immortal human monocyte-like cell line) to transforming growth factor-beta (TGF-beta) and to thrombin. Induction of uPAR mRNA occurred with TGF-beta (5 ng/mL) in a time-dependent fashion (P = .05; n = 4). Thrombin (5 National Institutes of Health [NIH] U/mL) increased uPAR mRNA by 2.8-fold above control (n = 4) without altering PAI-1 mRNA or protein synthesis (n = 4). The increase in uPAR gene expression in cells exposed to either TGF-beta or thrombin translated into a functional increase in cell-surface proteolytic activity. Under control conditions, U937 cells expressed PAI-2 but not PAI-1 mRNA. PAI-2 mRNA expression increased (P < .05; n = 4) with thrombin (5 NIH U/mL) but was suppressed by TGF-beta (5 ng/mL). TGF-beta induced PAI-1 mRNA within 6 hours accompanied by a 9-fold increase in PAI-1 protein from 6 hours (2.9 +/- 1.9 ng/mL) to 24 hours (20.0 +/- 9.6 ng/mL, P = .005; n = 3) paralleled by increased synthesis as shown in metabolic labeling experiments with 35S-methionine and immunoprecipitation of labeled PAI-1. PAI-1 mRNA and protein expression were seen in human coronary artery atherectomy specimens as well and were localized to analogous monocyte/macrophages and to smooth muscle cells as judged from results of in situ hybridization and immunocytochemistry studies.

CONCLUSIONS
The results indicate that there is induction of PAI-1 and uPAR in U937 cells exposed to TGF-beta and thrombin. In atheroma, analogous processes may modulate early migration of luminal monocytes into the subintimal space and proteolysis of ECM. Thus, cell surface, monocyte-directed fibrinolysis may influence atherosclerosis, restenosis, or both.
Recombinant apolipoprotein A-I Milano reduces intimal thickening after balloon injury in hypercholesterolemic rabbits.
Authors: Ameli S , Hultgardh-Nilsson A , Cercek B , Shah P K , Forrester J S , Ageland H , Nilsson J 
Published: June 2012

BACKGROUND
Several epidemiological studies have shown an inverse relation between high-density lipoprotein (HDL) cholesterol levels and coronary heart disease. Recently, observational studies have suggested a similar inverse relation between HDL and restenosis after coronary balloon angioplasty. Despite these observations, it is unclear whether this inverse relation reflects a direct vascular protective effect of HDL or apolipoprotein (apo) A-I, the major apolipoprotein component of HDL. Therefore, to determine whether HDL directly influences neointima formation, we investigated the effect of recombinant apo A-I Milano (apo A-I M), a mutant of human apo A-I with Arg-173 to Cys substitution, on intimal thickening after balloon injury in cholesterol-fed rabbits.

METHODS AND RESULTS
Cholesterol feeding was initiated 18 days before injury and continued until the time of death. Eight rabbits received intravenous injections of 40 mg of apo A-I M linked to a phospholipid carrier on alternate days, beginning 5 days before and continuing for 5 days after balloon injury of femoral and iliac arteries. Eight rabbits received the carrier alone, and four received neither apo A-I M nor the carrier. Three weeks after balloon injury, apo A-I M-treated rabbits had significantly reduced intimal thickness compared with the two control groups (mean +/- SD): 0.49 +/- 0.29 versus 1.14 +/- 0.38 mm2 and 1.69 +/- 0.43 mm2, P < .002 by ANOVA). The intima-to-media ratio was also significantly reduced by apo A-I M (0.7 +/- 0.2 versus 1.5 +/- 0.5 and 2.1 +/- 0.1, P < .002 by ANOVA) compared with the two controls. The fraction of intimal lesion covered by macrophages, as identified by immunohistochemistry using macrophage-specific monoclonal antibody, was significantly less in apo A-I M-treated rabbits compared with carrier-treated animals (25.3 +/- 17% versus 59.4 +/- 12.3%, P < .005). Aortic cholesterol content, measured in an additional 10 rabbits, did not differ significantly between apo A-I M-treated animals (n = 5) and carrier-treated controls (n = 5).

CONCLUSIONS
Apo A-I M significantly reduced intimal thickening and macrophage content after balloon injury in cholesterol-fed rabbits without a change in arterial total cholesterol content. Although the precise mechanism of action remains to be defined, these findings are consistent with a direct vascular effect of apo A-I, which could have potential therapeutic implications.
The renin-angiotensin system and volume overload-induced changes in cardiac collagen and elastin.
Authors: Ruzicka M , Keeley F W , Leenen F H 
Published: June 2012

BACKGROUND
Besides cardiac load, the renin-angiotensin system (RAS) and aldosterone may regulate collagen accumulation during maturation or hypertrophic growth. The effect of cardiac volume overload on both left ventricular (LV) and right ventricular (RV) collagen and elastin and the possible role of the RAS in such changes have not yet been assessed.

METHODS AND RESULTS
In the present study we assessed (1) the effects of 4 to 10 weeks of volume overload by an aortocaval shunt or minoxidil on LV and RV collagen and elastin and (2) the potential of the angiotensin-converting enzyme inhibitor enalapril and the angiotensin II receptor blocker losartan to prevent and regress volume overload-induced changes in cardiac collagen and elastin. Cardiac volume overload by aortocaval shunt or minoxidil treatment decreased LV collagen accumulation as compared with control rats. In contrast, RV collagen accumulation was potentiated during the initial weeks but not during chronic aortocaval shunt. Enalapril and losartan prevented the relative decreases in LV collagen content and concentration induced by a shunt. Losartan also reversed the decrease in LV collagen content by aortocaval shunt. Neither blocker significantly affected the enhanced RV collagen accumulation during the initial weeks of shunt, but both blockers further potentiated RV collagen accumulation during chronic volume overload. Aortocaval shunt for 4 weeks but not 10 weeks enhanced LV and RV elastin accumulation. This initial increase in LV and RV elastin content was blocked by both enalapril and losartan.

CONCLUSIONS
Cardiac volume overload, even when accompanied by increased plasma renin activity, decreases LV collagen accumulation, suggesting that in contrast to the stimulatory effect of systolic wall stress, increased diastolic wall stress inhibits collagen accumulation. In support of this concept, enalapril and losartan decreased LV preload and maintained LV collagen accumulation. In contrast to LV collagen, RV collagen accumulation was potentiated during the initial weeks of volume overload, possibly related to acute RV pressure overload shortly after aortocaval shunt and its decrease with chronic shunt. Enalapril and losartan had minimal effect on the enhanced RV collagen during the initial weeks of aortocaval shunt but potentiated RV collagen during chronic shunt, possibly by decreasing RV diastolic pressures. Altogether, these data suggest that during cardiac volume overload, the RAS affects cardiac collagen primarily by its hemodynamic effects. The RAS, however, may potentiate RV and LV elastin accumulation during the initial weeks of volume overload since both enalapril and losartan block this increase.