bluuebunny/crossref_metadata_2025 huggingface dataset:
Excess ldosterone Is Associated With Alterations of Myocardial Texture in Primary Aldosteronism
Authors: Rossi Gian Paolo , Di Bello Vitantonio , Ganzaroli Chiara , Sacchetto Alfredo , Cesari Maurizio , Bertini Alessio , Giorgi Davide , Scognamiglio Roldano , Mariani Mario , Pessina Achille C.
Published: July 2002

Hyperaldosteronism has been causally linked to myocardial interstitial fibrosis experimentally, but it remains unclear if this link also applies to humans. Thus, we investigated the effects of excess aldosterone due to primary aldosteronism (PA) on collagen deposition in the heart. We used echocardiography to estimate left ventricular (LV) wall thickness and dimensions and for videodensitometric analysis of myocardial texture in 17 consecutive patients with PA and 10 patients with primary (essential) hypertension who were matched for demographics, casual blood pressure, and known duration of hypertension. The groups differed in serum K
+
, ECG PQ interval duration, plasma renin activity, and aldosterone levels (all
P
≤0.002) but not for casual blood pressure values, demographics, and duration of hypertension. Compared with hypertensive patients, PA patients showed a higher LV mass index (53.7±1.8 versus 45.5±2.0 g/m
2.7
;
P
=0.008) and lower values of the cyclic variation index of the myocardial mean gray level of septum (CVI
s
; −12.02±5.84% versus 6.06±3.08%;
P
=0.012) and posterior wall (−11.13±6.42% versus 8.63±9.62%;
P
=0.012). A regression analysis showed that CVI
s
was predicted by the PQ duration, supine plasma renin activity, plasma aldosterone, and age, which collectively accounted for ≈36% of CVI
s
variance. PA is associated with alterations of myocardial textures that suggest increased collagen deposition and that can explain both the dependence of LV diastolic filling from presystole and the prolongation of the PQ interval.
Aspirin Prevents

Escherichia coli

Lipopolysaccharide– and

Staphylococcus aureus

–Induced Downregulation of Endothelial Nitric Oxide Synthase Expression in Guinea Pig Pericardial Tissue
Authors: Arriero Maria M. , de la Pinta Juan C. , Escribano Marta , Celdrán Angel , Muñoz-Alameda Luis , García-Cañete Joaquin , Jiménez Ana M. , Casado Santos , Farré Jerónimo , López-Farré Antonio
Published: July 2002

The aim was to analyze whether pericardial tissue expresses endothelial NO synthase (eNOS) protein and to determine the presence of cytosolic proteins that bind to eNOS mRNA. The effect of aspirin on the above-mentioned parameters was also analyzed. eNOS protein was expressed in pericardial tissue from male guinea pigs.
Escherichia coli
lipopolysaccharide (LPS, 10 μg/mL) and
Staphylococcus aureus
endotoxin (SA, 10 μg/mL) reduced eNOS protein expression and shortened the half-life of the eNOS messenger. Under basal conditions, cytosolic extracts from pericardial samples bound to the 3′-untranslated region (3′-UTR) of eNOS mRNA, which was enhanced by LPS and SA. Proteinase K fully prevented the binding of cytosolic pericardial extracts to 3′-UTR of eNOS mRNA, suggesting the involvement of proteins that were further characterized as 60- and 51-kDa proteins. Aspirin (1 to 10 mmol/L) restored eNOS expression in either LPS- and SA-stimulated pericardial samples and reduced the binding activity of the pericardial cytosolic proteins to 3′-UTR of eNOS mRNA. Indomethacin also reduced the downregulation of eNOS by LPS and diminished the binding activity of the cytosolic proteins, although higher doses of indomethacin than of aspirin were needed to improve these parameters. In conclusion, eNOS protein is expressed in guinea pig pericardial tissue. LPS and SA stimulate the binding activity of pericardial cytosolic proteins to 3′-UTR of eNOS mRNA and reduce eNOS protein expression. High doses of aspirin and indomethacin protect eNOS protein expression and reduce the binding activity of the cytosolic proteins to 3′-UTR of eNOS mRNA, suggesting an inverse association between the presence of these cytosolic proteins and eNOS expression.
Dynamic Modulation of Interendothelial Gap Junctional Communication by 11,12-Epoxyeicosatrienoic Acid
Authors: Popp Rüdiger , Brandes Ralf P. , Ott Gregor , Busse Rudi , Fleming Ingrid
Published: July 2002

Functional gap junctional communication between vascular cells has been implicated in ascending dilatation and the cytochrome P-450 (CYP) inhibitor–sensitive and NO- and prostacyclin-independent dilatation of many vascular beds. Here, we assessed the mechanisms by which the epoxyeicosatrienoic acids (EETs) generated by a CYP 2C enzyme control interendothelial gap junctional communication. In CYP 2C–expressing porcine coronary endothelial cells, bradykinin, which enhances EET formation, elicited a biphasic effect on the electrical coupling and transfer of Lucifer yellow between endothelial cells, consisting of a transient increase in coupling followed by a sustained uncoupling. The initial phase was sensitive to the CYP 2C9 inhibitor sulfaphenazole and the protein kinase A (PKA) inhibitors Rp-cAMPS and KT5720 and could be mimicked by forskolin and caged cAMP as well as by the PKA activators 5,6-dichloro-1-β-
d
-ribofuranosylbenzimidazole 3′,5′-cyclic monophosphorothioate sodium salt and Sp-cAMPS. Gap junction uncoupling in bradykinin-stimulated porcine coronary endothelial cells was prevented by inhibiting the activation of extracellular signal–regulated kinase (ERK)1/2. In human endothelial cells, which express little CYP 2C, bradykinin elicited only an ERK1/2-mediated inhibition of intercellular communication. The CYP 2C9 product, 11,12-EET, also exerted a dual effect on the electrical and dye coupling of human endothelial cells, which was sensitive to PKA inhibition. These results demonstrate that an agonist-activated CYP-dependent pathway as well as 11,12-EET can positively regulate interendothelial gap junctional communication, most probably via the activation of PKA, an effect that is curtailed by the subsequent activation of ERK1/2.
Ionic Current Basis of Electrocardiographic Waveforms
Authors: Gima Kazutaka , Rudy Yoram
Published: July 2002

Body surface electrocardiograms and electrograms recorded from the surfaces of the heart are the basis for diagnosis and treatment of cardiac electrophysiological disorders and arrhythmias. Given recent advances in understanding the molecular mechanisms of arrhythmia, it is important to relate these electrocardiographic waveforms to cellular electrophysiological processes. This modeling study establishes the following principles: (1) voltage gradients created by heterogeneities of the slow-delayed rectifier (
I
Ks
) and transient outward (
I
to
) potassium current inscribe the T wave and J wave, respectively; T-wave polarity and width are strongly influenced by the degree of intercellular coupling through gap-junctions. (2) Changes in [K
+
]
o
modulate the T wave through their effect on the rapid-delayed rectifier,
I
Kr
. (3) Alterations of
I
Ks
,
I
Kr
, and
I
Na
(fast sodium current) in long-QT syndrome (LQT1, LQT2, and LQT3, respectively) are reflected in characteristic QT-interval and T-wave changes; LQT1 prolongs QT without widening the T wave. (4) Accelerated inactivation of
I
Na
on the background of large epicardial
I
to
results in ST elevation (Brugada phenotype) that reflects the degree of severity. (5) Activation of the ATP-sensitive potassium current,
I
K(ATP)
, is sufficient to cause ST elevation during acute ischemia. These principles provide a mechanistic cellular basis for interpretation of electrocardiographic waveforms.
Functional Roles of Ca
v
1.3 (α
1D
) Calcium Channel in Sinoatrial Nodes
Authors: Zhang Zhao , Xu Yanfang , Song Haitao , Rodriguez Jennifer , Tuteja Dipika , Namkung Yoon , Shin Hee-Sup , Chiamvimonvat Nipavan
Published: July 2002

We directly examined the role of the Ca
v
1.3 (α
1D
) Ca
2+
channel in the sinoatrial (SA) node by using Ca
v
1.3 Ca
2+
channel-deficient mice. A previous report has shown that the null mutant (Ca
v
1.3
−/−
) mice have sinus bradycardia with a prolonged PR interval. In the present study, we show that spontaneous action potentials recorded from the SA nodes show a significant decrease in the beating frequency and rate of diastolic depolarization in Ca
v
1.3
−/−
mice compared with their heterozygous (Ca
v
1.3
+/−
) or wild-type (WT, Ca
v
1.3
+/+
) littermates, suggesting that the deficit is intrinsic to the SA node. Whole-cell L-type Ca
2+
currents (
I
Ca,L
s) recorded in single isolated SA node cells from Ca
v
1.3
−/−
mice show a significant depolarization shift in the activation threshold. The voltage-dependent activation of Ca
v
1.2 (α
1C
) versus Ca
v
1.3 Ca
2+
channel subunits was directly compared by using a heterologous expression system without β coexpression. Similar to the
I
Ca,L
recorded in the SA node of Ca
v
1.3
−/−
mutant mice, the Ca
v
1.2 Ca
2+
channel shows a depolarization shift in the voltage-dependent activation compared with that in the Ca
v
1.3 Ca
2+
channel. In summary, using gene-targeted deletion of the Ca
v
1.3 Ca
2+
channel, we were able to establish a role for Ca
v
1.3 Ca
2+
channels in the generation of the spontaneous action potential in SA node cells.
Actin Capping Protein
Authors: Pyle W. Glen , Hart Marilyn C. , Cooper John A. , Sumandea Marius P. , de Tombe Pieter P. , Solaro R. John
Published: July 2002

Actin capping protein (CapZ) binds the barbed ends of actin at sarcomeric Z-lines. In addition to anchoring actin, Z-discs bind protein kinase C (PKC). Although CapZ is crucial for myofibrillogenesis, its role in muscle function and intracellular signaling is unknown. We hypothesized that CapZ downregulation would impair myocardial function and disrupt PKC-myofilament signaling by impairing PKC–Z-disc interaction. To test these hypotheses, we examined transgenic (TG) mice in which cardiac CapZ protein is reduced. Fiber bundles were dissected from papillary muscles and detergent extracted. Some fiber bundles were treated with PKC activators phenylephrine (PHE) or endothelin (ET) before detergent extraction. We simultaneously measured Ca
2+
-dependent tension and actomyosin MgATPase activity. CapZ downregulation increased myofilament Ca
2+
sensitivity without affecting maximum tension or actomyosin MgATPase activity. Maximum tension and actomyosin MgATPase activity were decreased after PHE or ET treatment of wild-type (WT) muscle. Fiber bundles from TG hearts did not respond to PHE or ET. Immunoblot analysis revealed an increase in myofilament-associated PKC-ε after PHE or ET exposure of WT preparations. In contrast, myofilament-associated PKC-ε was decreased after PHE or ET treatment in TG myocardium. Protein levels of myofilament-associated PKC-β were decreased in TG ventricle. C-protein and troponin I phosphorylation was increased after PHE or ET treatment in WT and TG hearts. Basal phosphorylation levels of C-protein and troponin I were higher in TG myocardium. These results indicate that downregulation of CapZ, or other changes associated with CapZ downregulation, increases cardiac myofilament Ca
2+
sensitivity, inhibits PKC-mediated control of myofilament activation, and decreases myofilament-associated PKC-β.
Nip21 Gene Expression Reduces Coxsackievirus B3 Replication by Promoting Apoptotic Cell Death via a Mitochondria-Dependent Pathway
Authors: Zhang Huifang M. , Yanagawa Bobby , Cheung Paul , Luo Honglin , Yuan Ji , Chau David , Wang Aikun , Bohunek Lubos , Wilson Janet E. , McManus Bruce M. , Yang Decheng
Published: July 2002

Our previous studies, using differential mRNA display, suggested that the mouse Nip21 gene may be involved in myocarditis development in the coxsackievirus B3 (CVB3)–infected mouse heart. Sequence comparison indicated that the mouse Nip21 gene shares high sequence homology to human Nip2. This human protein is known to interact with both the apoptosis inhibitor Bcl-2 and a homologous protein, the adenovirus E1B 19-kDa protein. Such interactions implicate Nip21 gene in cell death pathways. To study the function of this gene, we have cloned Nip21 from mouse hearts and established a Tet-On doxycycline-inducible HeLa cell line and a cardiomyocyte H9c2 cell line expressing Nip21 to characterize gene function in relation to apoptosis. We demonstrated that Nip21 expression could induce apoptosis via caspase-depended mitochondria activation. To further determine the function of Nip21 in CVB3-induced apoptosis, the Tet-On/Nip21 HeLa cell line was induced by doxycycline followed by CVB3 infection. We found that activation of caspase-3 and cleavage of poly-(ADP-ribose) polymerase occurred 2 hours earlier than in vector-transfected control cells, suggesting that Nip21 expression enhances CVB3-induced apoptosis. We also demonstrated a significant decrease in HeLa cell and H9c2 cell viability. Particularly, as illustrated by viral plaque assay, CVB3 replication was dramatically reduced in Tet-On HeLa cells, due at least in part to the earlier killing of the host cells by Nip21 overexpression.
Analysis and Comparison of the Psychometric Properties of Three Balance Measures for Stroke Patients
Authors: Mao Hui-Fen , Hsueh I-Ping , Tang Pei-Fang , Sheu Ching-Fan , Hsieh Ching-Lin
Published: July 2002

Background and Purpose—This study compared the psychometric properties of 3 clinical balance measures, the Berg Balance Scale (BBS), the Balance subscale of the Fugl-Meyer test (FM-B), and the Postural Assessment Scale for Stroke Patients (PASS), in stroke patients with a broad range of neurological and functional impairment from the acute stage up to 180 days after onset.

Methods—One hundred twenty-three stroke patients were followed up prospectively with the 3 balance measures 14, 30, 90, and 180 days after stroke onset (DAS). Reliability (interrater reliability and internal consistency) and validity (concurrent validity, convergent validity, and predictive validity) of each measure were examined. A comparison of the responsiveness of each of the 3 measures was made on the basis of the entire group of patients and 3 separate groups classified by degree of neurological severity.

Results—The FM-B and BBS showed a significant floor or ceiling effect at some DAS points, whereas the PASS did not show these effects. The BBS, FM-B, and PASS all had good reliability and validity for patients at different recovery stages after stroke. The results of effect size demonstrated fair to good responsiveness of all 3 measures within the first 90 DAS but, as expected, only a low level of responsiveness at 90 to 180 DAS. The PASS was more responsive to changes in severe stroke patients at the earliest period after stroke onset, 14 to 30 DAS.

Conclusions—All 3 measures tested showed very acceptable levels of reliability, validity, and responsiveness for both clinicians and researchers. The PASS showed slightly better psychometric characteristics than the other 2 measures.
Hypertensive Pontine Microhemorrhage
Authors: Jeong Jee-Hyang , Yoon Soo Jin , Kang Sue J. , Choi Kyung Gyu , Na Duk L.
Published: July 2002

Background and Purpose

—

This study investigated whether the topography of hypertensive pontine microhemorrhages (hPMHs) resembles that of larger primary pontine hemorrhages.

Methods

—

Sixty-nine consecutive patients with small-vessel disease underwent imaging with gradient-echo MRI, and 27 patients with hPMH were detected. Lesion size and location along the rostrocaudal (longitudinal), lateral (coronal), and anteroposterior (sagittal) axes were determined.

Results

—

A total of 52 hPMHs were identified in the 27 patients (mean, 1.93±2.4 per patient). The lesions showed a nonrandom distribution, with a propensity to occur in the middle pons in the rostrocaudal axis, posterior half of the basis pontis in the anteroposterior axis, and central subdivision within the lateral axis. The area of hPMH ranged from 1.3 to 19.0 mm
2
(mean, 5.06±3.72 mm
2
). The size of hPMH did not vary as a function of lesion location.

Conclusions

—

Previous studies reported that primary pontine hemorrhages tend to occur in the middle pons and at the junction of basis pontis and tegmentum. Therefore, topographical correspondences between large and small pontine hemorrhages may provide evidence that the 2 lesions share some etiological basis. Further investigation may determine whether hPMHs portend future symptomatic primary pontine hemorrhages.
Detection of Deoxygenation-Related Signal Change in Acute Ischemic Stroke Patients by T2*-Weighted Magnetic Resonance Imaging
Authors: Tamura Hajime , Hatazawa Jun , Toyoshima Hideto , Shimosegawa Eku , Okudera Toshio
Published: July 2002

Background and Purpose

—

Acute decreases in the MR T2*-weighted signal have been reported in experimental models of middle cerebral artery occlusion. This has been attributed to blood deoxygenation in association with an increased brain oxygen extraction fraction. The aim of this study was to detect this signal by susceptibility-weighted MR imaging in acute ischemic stroke patients.

Methods

—

Dynamic susceptibility contrast-enhanced MR (DSC-MR) imaging was performed within 4 hours of stroke onset in 6 patients with unilateral cerebral artery occlusion (middle cerebral artery, n=5; internal carotid artery, n=1). Cerebral blood volume was estimated on a pixel-by-pixel basis. DSC-MR images taken before arrival of the contrast medium were examined visually to identify hypointense areas. Bilateral regions of interest were set in the middle cerebral artery territory for comparison of the mean signal intensity. A semilogarithmic plot of signal intensity versus cerebral blood volume for every pixel in the region of interest was also analyzed.

Results

—

The side on which the hypointense area was seen was significantly correlated with the side of arterial occlusion. The mean signal intensity was significantly smaller on the affected side than on the contralateral side. The semilogarithmic plot of signal intensity versus cerebral blood volume indicated greater deoxyhemoglobin concentrations for the ipsilateral than for the contralateral region of interest.

Conclusions

—

DSC-MR images allow detection of hypointensity in the affected cerebral hemisphere in acute ischemic stroke patients. Such hypointensity may indicate increased oxygen extraction fraction (misery perfusion) and may provide information valuable to patient care.
Brain Representation of Hemifield Stimulation in Poststroke Visual Field Defects
Authors: Nelles Gereon , Widman Guido , de Greiff Armin , Meistrowitz Anette , Dimitrova Albena , Weber Johannes , Forsting Michael , Esser Joachim , Diener H. Christoph
Published: July 2002

Background and Purpose

—

Plasticity in extended, parallel, or reciprocal operating networks is well recognized. Changes in neuronal activity after lesions to distinct localized structures, such as the primary visual cortex, are less well characterized. We investigated the cortical reorganization in patients with poststroke visual field defects using blood oxygen level–dependent functional MRI.

Methods

—

Brain activation was measured in 7 patients with a single occipital cortical lesion and partially recovered hemianopia and in 7 age-matched control subjects. Differences in activation between rest and visual hemifield stimulation were assessed with statistical parametric mapping (SPM’99).

Results

—

In normal subjects, significant activation was found in the contralateral primary visual cortex and bilaterally in the extrastriate cortex. During hemifield stimulation of the unaffected side of stroke patients, a similar pattern was found compared with that seen in control subjects. During stimulation of the hemianopic side, bilateral activation was seen within the extrastriate cortex, stronger in the ipsilateral hemisphere. The primary visual cortex was not significantly activated in either hemisphere during stimulation of the hemianopic side.

Conclusions

—

Visual field defects after stroke are associated with bilateral activation of the extrastriate visual cortex. This pattern of activation indicates altered neuronal activity in the visual system. Further investigation is necessary to determine the relationship between functional reorganization and recovery of lost visual function after poststroke hemianopia.
Endovascular Microcoil Gene Delivery Using Immobilized Anti-adenovirus Antibody for Vector Tethering
Authors: Abrahams John M. , Song Cunxian , DeFelice Suzanne , Grady M. Sean , Diamond Scott L. , Levy Robert J.
Published: July 2002

Background and Purpose

—

Endovascular microcoils are widely used in interventional procedures to treat cerebral aneurysms. In the present study we report for the first time successful use of an endovascular microcoil as a gene delivery system.

Methods

—

Anti-adenoviral monoclonal antibodies were covalently attached to the collagen-coated surface of either platinum or polyglycolic acid microcoils. These antibodies were used to tether replication-deficient adenovirus (Ad-GFP [encoding green fluorescent protein] or Ad-LacZ [encoding β-galactosidase]). Cell culture studies with rat arterial smooth muscle cells (A10) assessed transduction on or near the coil. Platinum coils coated with Ad-GFP were implanted into the ligated common carotid artery (CCA) of adult rats in a model of arterial stasis and pressurization. After 7 days, CCA segments were harvested, and coils were removed for histopathology and GFP expression studies, while organs were evaluated by polymerase chain reaction to assess viral biodistribution.

Results

—

In cell culture studies, GFP-positive smooth muscle cells were detected only on the platinum coil surface, while LacZ-positive cells were detected only on the polyglycolic acid coil surface, thus demonstrating localized gene delivery. After 7-day implantation, GFP (according to fluorescence microscopy and confirmed with immunohistochemistry) was detected on the harvested platinum coil and in the organizing thrombus within the CCA but not in the arterial wall. Morphometric analyses revealed that 13.3+2.0% of cells within the organized thrombus were transduced with Ad-GFP via the gene delivery system. However, arterial smooth muscle cells were negative for GFP according to fluorescence microscopy and immunohistochemistry. Ad-GFP was not detectable by polymerase chain reaction in lung, liver, or kidney.

Conclusions

—

It is concluded that catheter deployment of platinum or biodegradable gene delivery endovascular microcoils represents an interventional device–based gene therapy system that can serve as a suitable platform for either single or multiple gene therapy vectors.
Chlamydia pneumoniae

Serology Is Associated With Thrombosis-Related but Not With Plaque-Related Microembolization During Carotid Endarterectomy
Authors: Vainas Tryfon , Kurvers Harrie A.J.M. , Mess Werner H. , Graaf Rick de , Ezzahiri Rajaa , Tordoir Jan H.M. , Schurink Geert-Willem H. , Bruggeman Cathrien A. , Kitslaar Peter J.E.H.M.
Published: July 2002

Background and Purpose

—

Chlamydia pneumoniae
has repeatedly been associated with atherosclerotic disease. Our study was designed to clarify whether this association is based on
C pneumoniae
-induced transformation of a stable into an unstable atherosclerotic plaque or on stimulation of hypercoagulability leading to increased thrombotic arterial occlusions by
C pneumoniae
infection. Transcranial Doppler ultrasonographic monitoring of the middle cerebral artery during carotid endarterectomy offers the opportunity to study, before removal of the plaque, atherothrombotic emboli dislodging from an unstable carotid plaque (plaque-related emboli) and emboli related to (excessive) thrombus formation at the endarterectomy site after removal of the plaque and restoration of flow (thrombosis-related emboli).

Methods

—

C pneumoniae
IgA (≥1/16) and IgG (≥1/64) seropositivity was assessed in 53 patients with symptomatic carotid artery disease undergoing carotid endarterectomy. The removed carotid plaques were studied histologically to assess plaque instability.

Results

—

Plaque- and thrombosis-related emboli were registered in 43 patients with an adequate transtemporal window. IgA seropositivity (58%) was associated significantly with thrombosis-related embolization (
P
=0.030) but not with plaque-related embolization or with histological plaque instability.

Conclusions

—

C pneumoniae
serology is associated with microembolization after endarterectomy and restoration of flow. Since these microemboli represent platelet aggregations and are related to cerebrovascular complications, our data suggest that
C pneumoniae
infection contributes to cerebrovascular events in patients with carotid artery disease through stimulation of thrombosis.
Dietary Intake of Folate and Risk of Stroke in US Men and Women
Authors: Bazzano Lydia A. , He Jiang , Ogden Lorraine G. , Loria Catherine , Vupputuri Suma , Myers Leann , Whelton Paul K.
Published: July 2002

Background and Purpose

—

Few population-based studies have examined the relationship between dietary intake of folate and risk of stroke and cardiovascular disease (CVD). This study examines the association between dietary intake of folate and the subsequent risk of stroke and CVD.

Methods

—

Study participants included 9764 US men and women aged 25 to 74 years who participated in the National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study (NHEFS) and were free of CVD at baseline. Dietary intake of folate was assessed at baseline using a 24-hour dietary recall and calculated using ESHA software. Incidence data for stroke and CVD were obtained from medical records and death certificates.

Results

—

Over an average of 19 years of follow-up, 926 incident stroke events and 3758 incident CVD events were documented. The relative risk (RR) was 0.79 (95% confidence interval [CI], 0.63 to 0.99,
P
=0.03 for trend) for incident stroke events and 0.86 (95% CI: 0.78 to 0.95,
P
<0.001 for trend) for incident CVD events in the highest quartile of dietary folate intake (median, 405.0 μg/day) compared with those in the lowest quartile (median, 99.0 μg/day), after adjustment for established cardiovascular risk factors and dietary factors.

Conclusions

—

Our findings indicate an inverse relationship between dietary intake of folate and subsequent risk of stroke and CVD. Increasing dietary intake of folate from food sources may be an important approach to the prevention of CVD in the US population.
Endovascular Coil Embolization of Cerebral Aneurysm Remnants After Incomplete Surgical Obliteration
Authors: Rabinstein Alejandro A. , Nichols Douglas A.
Published: July 2002

Introduction

—

The presence of an aneurysm remnant after incomplete or unsuccessful surgical clipping is associated with persistent risk of regrowth and rupture, and additional treatment is generally recommended. Attempts at surgical re-exploration are technically difficult and carry significant risk. Endovascular therapy can represent a valuable therapeutic alterative in these cases.

Methods

—

We reviewed the information on 21 patients with postsurgical aneurysm remnants treated at our institution with endovascular coil occlusion between 1991 and 2000. Clinical outcome was measured using the modified Rankin scale. Statistical analysis of outcome predictors was performed using the two-tailed Fisher exact test.

Results

—

Sixty-seven percent of the aneurysms were located in the anterior circulation. The median aneurysm size at the time of surgery was 9.9 mm (range 3 to 35 mm). The mean size of the aneurysm remnants before coiling was 6.4 mm (range 3 to 14 mm). Endovascular coiling resulted in total occlusion of the remnants in 81% of the cases. No major complications were associated with the endovascular treatment. Seventy-two percent of patients left the hospital without any functional impairment (modified Rankin scale 0 to 1). No cases of subarachnoid hemorrhage or symptomatic aneurysmal regrowth were noted after endovascular treatment over a mean follow-up of 22 months. Presence of disability or death was associated with an initial (presurgical) presentation with subarachnoid hemorrhage (
P
=0.04) and an interval between incomplete clipping and endovascular coil embolization ≤1 month (
P
= 0.0005).

Conclusion

—

Endovascular coil occlusion of postsurgical aneurysm remnants is a safe and efficacious therapeutic alternative in selected cases. Postoperative angiography to identify aneurysm remnants that may be amenable to endovascular treatment should be considered in all patients.
Folic Acid Improves Endothelial Function in Coronary Artery Disease via Mechanisms Largely Independent of Homocysteine Lowering
Authors: Doshi Sagar N. , McDowell Ian F.W. , Moat Stuart J. , Payne Nicola , Durrant Hilary J. , Lewis Malcolm J. , Goodfellow Jonathan
Published: July 2002

Background
—

Homocysteine is a risk factor for coronary artery disease (CAD), although a causal relation remains to be proven. The importance of determining direct causality rests in the fact that plasma homocysteine can be safely and inexpensively reduced by 25% with folic acid. This reduction is maximally achieved by doses of 0.4 mg/d. High-dose folic acid (5 mg/d) improves endothelial function in CAD, although the mechanism is controversial. It has been proposed that improvement occurs through reduction in total (tHcy) or free (non–protein bound) homocysteine (fHcy). We investigated the effects of folic acid on endothelial function before a change in homocysteine in patients with CAD.

Methods and Results
—

A randomized, placebo-controlled study of folic acid (5 mg/d) for 6 weeks was undertaken in 33 patients. Endothelial function, assessed by flow-mediated dilatation (FMD), was measured before, at 2 and 4 hours after the first dose of folic acid, and after 6 weeks of treatment. Plasma folate increased markedly by 1 hour (200 compared with 25.8 nmol/L;
P
<0.001). FMD improved at 2 hours (83 compared with 47 μm;
P
<0.001) and was largely complete by 4 hours (101 compared with 51 μm;
P
<0.001). tHcy did not significantly differ acutely (4-hour tHcy, 9.56 compared with 9.79 μmol/L;
P
=NS). fHcy did not differ at 3 hours but was slightly reduced at 4 hours (1.55 compared with 1.78 μmol/L;
P
=0.02). FMD improvement did not correlate with reductions in either fHcy or tHcy at any time.

Conclusions
—

These data suggest that folic acid improves endothelial function in CAD acutely by a mechanism largely independent of homocysteine.
Nitric Oxide Regulates Local Arterial Distensibility In Vivo
Authors: Wilkinson Ian B. , Qasem Ahmed , McEniery Carmel M. , Webb David J. , Avolio Albert P. , Cockcroft John R.
Published: July 2002

Background
—

Arterial stiffness is an important determinant of cardiovascular risk. Several lines of evidence support a role for the endothelium in regulating arterial stiffness by release of vasoactive mediators. We hypothesized that nitric oxide (NO) acting locally regulates arterial stiffness in vivo, and the aim of this experiment was to test this hypothesis in an ovine hind-limb preparation.

Methods and Results
—

All studies were conducted in anesthetized sheep. Pulse wave velocity (PWV) was calculated by the foot-to-foot methodology from 2 pressure waveforms recorded simultaneously with a high-fidelity dual pressure-sensing catheter placed in the common iliac artery. Intra-arterial infusion of
N
G
-monomethyl-
l
-arginine (L-NMMA) increased iliac PWV significantly, by 3±2% (
P
<0.01). Infusion of acetylcholine and glyceryl trinitrate reduced PWV significantly, by 6±4% (
P
=0.03) and 5±2% (
P
<0.01), respectively. Only the effect of acetylcholine, however, was significantly inhibited during coinfusion of L-NMMA (
P
=0.03). There was no change in systemic arterial pressure throughout the studies. Importantly, infusion of L-NMMA or acetylcholine distal to the common iliac artery (via the sheath) did not affect PWV.

Conclusions
—

These results demonstrate, for the first time, that basal NO production influences large-artery distensibility. In addition, exogenous acetylcholine and glyceryl trinitrate both increase arterial distensibility, the former mainly through NO production. This may help explain why conditions that exhibit endothelial dysfunction are also associated with increased arterial stiffness. Therefore, reversal of endothelial dysfunction or drugs that are large-artery vasorelaxants may be effective in reducing large-artery stiffness in humans, and thus cardiovascular risk.
Prognostic Role of Myocardial Blood Flow Impairment in Idiopathic Left Ventricular Dysfunction
Authors: Neglia Danilo , Michelassi Claudio , Trivieri Maria Giovanna , Sambuceti Gianmario , Giorgetti Assuero , Pratali Lorenza , Gallopin Michela , Salvadori Piero , Sorace Oreste , Carpeggiani Clara , Poddighe Rosa , L’Abbate Antonio , Parodi Oberdan
Published: July 2002

Background
—

Depressed myocardial blood flow (MBF) has been reported in dilated cardiomyopathy. The aim of this study was to investigate whether MBF impairment is an independent predictor of prognosis in patients with idiopathic left ventricular (LV) dysfunction.

Methods and Results
—

Sixty-seven patients (52 male, mean age 52±12 years) with different degrees of idiopathic LV systolic dysfunction (average LV ejection fraction, 0.34±0.10; range, 0.07 to 0.49) were prospectively enrolled. Thirty-four subjects (51%) had no history of heart failure symptoms at enrollment (NYHA class I). All patients underwent clinical and functional evaluation and a PET study to measure absolute MBF at rest and after intravenous dipyridamole. During a mean follow-up of 45±37 months, 24 patients had major cardiac events, including cardiac death in 8 and development or progression of heart failure in 16 patients. Multivariate regression analysis (Cox proportional hazards model) revealed heart rate (χ
2
11.06,
P
<0.001), LV end-diastolic dimension (χ
2
11.73,
P
<0.001), and dipyridamole MBF (χ
2
11.04,
P
<0.001) as independent predictors of subsequent cardiac events. Dipyridamole MBF ≤1.36 mL · min
−1
· g
−1
was associated with an increase in the relative risk of death, development, or progression of heart failure of 3.5 times over other more common clinical and functional variables.

Conclusions
—

The present study demonstrates that severely depressed MBF is a predictor of poor prognosis in patients with idiopathic LV dysfunction independently of the degree of LV functional impairment and of the presence of overt heart failure.
Identification of Fibrous Cap Rupture With Magnetic Resonance Imaging Is Highly Associated With Recent Transient Ischemic Attack or Stroke
Authors: Yuan Chun , Zhang Shao-xiong , Polissar Nayak L. , Echelard Denise , Ortiz Geraldo , Davis Joseph W. , Ellington Elizabeth , Ferguson Marina S. , Hatsukami Thomas S.
Published: July 2002

Background
—

High-resolution MRI has been shown to be capable of distinguishing intact, thick fibrous caps from thin and ruptured caps in human carotid atherosclerosis in vivo. The aim of this study was to determine whether MRI identification of fibrous cap thinning or rupture is associated with a history of recent transient ischemic attack (TIA) or stroke.

Methods and Results
—

Fifty-three consecutive patients (mean age, 71 years; 49 male) scheduled for carotid endarterectomy were recruited after obtaining informed consent. Twenty-eight subjects had a recent history of TIA or stroke on the side appropriate to the index carotid lesion, and 25 were asymptomatic. Preoperative carotid MRI was performed in a 1.5-T GE Signa scanner that generated T
1
-, PD-, and T
2
-weighted and three-dimensional time-of-flight images. Using previously reported MRI criteria, the fibrous cap was categorized as intact-thick, intact-thin, or ruptured for each carotid plaque by blinded review. There was a strong and statistically significant trend showing a higher percentage of symptomatic patients for ruptured caps (70%) compared with thick caps (9%) (
P
=0.001 Mann-Whitney test for cap status versus symptoms). Compared with patients with thick fibrous caps, patients with ruptured caps were 23 times more likely to have had a recent TIA or stroke (95% CI=3, 210).

Conclusions
—

MRI identification of a ruptured fibrous cap is highly associated with a recent history of TIA or stroke. Ongoing prospective studies will determine the predictive value fibrous cap characteristics, as visualized by MRI, for risk of subsequent ischemic events.
Influence of Pyruvate on Contractile Performance and Ca
2+
Cycling in Isolated Failing Human Myocardium
Authors: Hasenfuss Gerd , Maier Lars S. , Hermann Hans-Peter , LÜers Claus , HÜnlich Mark , Zeitz Oliver , Janssen Paul M.L. , Pieske Burkert
Published: July 2002

Background
—

Application of pyruvate was shown to improve contractile function in isolated animal myocardium and hemodynamics in patients with congestive heart failure. We assessed the influence of pyruvate on systolic and diastolic myocardial function and its subcellular mode of action in isolated myocardium from end-stage failing human hearts.

Methods and Results
—

In muscle strip preparations, concentration-dependent effects of pyruvate on developed and diastolic force (n=6), aequorin light emission reflecting intracellular Ca
2+
transients (n=6), and rapid cooling contractures reflecting sarcoplasmic reticulum (SR) Ca
2+
content (n=11) were measured. Pyruvate resulted in a concentration-dependent increase in developed force and a decrease in diastolic force, with a maximum effect of 155% and 21%, respectively, at 20 mmol/L pyruvate (
P
<0.05). This was associated with a dose-dependent prolongation of time to peak tension and relaxation time. Pyruvate increased rapid cooling contractures by 51% and aequorin light signals by 85% (at 15 and 20 mmol/L;
P
<0.05). This indicates increased SR Ca
2+
content and increased intracellular Ca
2+
transients. The inotropic effect of pyruvate was still present after elimination of SR Ca
2+
storage function with 10 μmol/L cyclopiazonic acid and 1 μmol/L ryanodine (n=8). Pyruvate significantly increased intracellular pH from 7.31±0.03 to 7.40±0.04 by BCECF fluorescence (n=6).

Conclusions
—

The present findings indicate that pyruvate improves contractile performance of failing human myocardium by increasing intracellular Ca
2+
transients as well as myofilament Ca
2+
sensitivity. The former seem to result from increased SR Ca
2+
accumulation and release, the latter from increased intracellular pH.
Shortened Head-Up Tilting Test Guided by Systolic Pressure Reductions in Neurocardiogenic Syncope
Authors: Pitzalis Mariavittoria , Massari Francesco , Guida Pietro , Iacoviello Massimo , Mastropasqua Filippo , Rizzon Brian , Forleo Cinzia , Rizzon Paolo
Published: July 2002

Background
—

Asymptomatic reductions in arterial pressure have been reported to occur before the onset of tilt-induced syncope. We investigated the predictive value of these reductions for a positive tilt result.

Methods and Results
—

In a first study, 238 consecutive healthy subjects with unexplained syncope underwent a passive tilt table test. Finger systolic arterial pressure (SAP) recordings made it possible to calculate how many of the beat-to-beat SAP values during the first 15 minutes of tilt were lower than the lowest value recorded at baseline. Neurocardiogenic syncope was diagnosed in 73 subjects; 28 fainted after 15 minutes of tilt and experienced more pressure reductions than did the subjects with a negative test (328±400 versus 119±284;
P
<0.01). More than 14 SAP reductions during the first 15 minutes of tilt allowed us to predict a positive test with 93% sensitivity, 58% specificity, and positive and negative predictive values of 28% and 98%, respectively. In a second prospective study (80 consecutive subjects), the online analysis of this criterion by visually inspecting a Finapres monitor showed 80% sensitivity, 85% specificity, and positive and negative predictive values of 57% and 94%.

Conclusions
—

In healthy subjects with unexplained syncope, the evaluation of SAP reductions during the first 15 minutes of tilt is a marker of systolic pressure instability preceding syncope and constitutes a simple and good predictor of tilt outcome that could be used to guide test duration.
Loss of Preconditioning by Attenuated Activation of Myocardial ATP-Sensitive Potassium Channels in Elderly Patients Undergoing Coronary Angioplasty
Authors: Lee Tsung-Ming , Su Sheng-Fang , Chou Tsai-Fwu , Lee Yuan-Teh , Tsai Chang-Her
Published: July 2002

Background

—

The ischemic preconditioning response among elderly patients is known to be lower than in adult patients. Since mitochondrial ATP-sensitive potassium (K
ATP
) channels exert preconditioning effects, we undertook this study to determine whether this attenuated activation of K
ATP
channels influences the reduced responsiveness of elderly patients to ischemic preconditioning.

Methods and Results

—

Fifty-six patients undergoing angioplasty for a major epicardial coronary artery were randomly allocated to either an ischemic preconditioning group, a nicorandil (an agonist of K
ATP
channels) group, or a glibenclamide (an antagonist of K
ATP
channels), group based on their age: adult groups (n=26; age, ≤55 years; mean age, 45±5 years) and elderly groups (n=30; age, ≥65 years; mean age, 71±3 years). Ischemic preconditioning with a 120-second coronary occlusion significantly lowered the ischemic burden assessed by ST-segment shift, chest pain score, and myocardial lactate extraction ratios in the adult group. This did not occur in the elderly group. The impaired preconditioning responsiveness in the elderly patients was reversed by nicorandil administration or an ischemic period lengthened to 180 seconds. However, nicorandil-induced cardioprotection was abolished by administering glibenclamide in both the adult and elderly groups.

Conclusions

—

The present study demonstrates that preconditioning significantly enhances the tolerance of the heart to subsequent ischemia in adults but not in senescent patients. Since prolonged ischemia and nicorandil are able to mimic preconditioning and can reverse impaired responsiveness, impaired preconditioning of the aged heart appears to be due to an attenuated activation of K
ATP
channels.
Selective Norepinephrine Reuptake Inhibition as a Human Model of Orthostatic Intolerance
Authors: Schroeder Christoph , Tank Jens , Boschmann Michael , Diedrich Andre , Sharma Arya M. , Biaggioni Italo , Luft Friedrich C. , Jordan Jens
Published: July 2002

Background

—

Observations in patients with functional mutations of the norepinephrine transporter (NET) gene suggest that impaired norepinephrine uptake may contribute to idiopathic orthostatic intolerance.

Methods and Results

—

We studied the effect of the selective NET blocker reboxetine and placebo in a randomized, double-blind, crossover fashion on cardiovascular responses to cold pressor testing, handgrip testing, and a graded head-up tilt test (HUT) in 18 healthy subjects. In a subset, we determined isoproterenol and phenylephrine sensitivities. Subjects ingested 8 mg reboxetine or placebo 12 hours and 1 hour before testing. In the supine position, heart rate was 65±2 bpm with placebo and 71±3 bpm with reboxetine. At 75° HUT, heart rate was 84±3 and 119±4 bpm with placebo and with reboxetine (
P
<0.0001). Mean arterial pressure was 85±2 with placebo and 91±2 mm Hg with reboxetine while supine (
P
<0.01) and 88±2 mm Hg and 90±3 mm Hg at 75° HUT. Blood pressure responses to cold pressor and handgrip testing were attenuated with reboxetine. Reboxetine increased the sensitivity to the chronotropic effect of isoproterenol and the pressor effect of phenylephrine. Vasovagal reactions occurred in 9 subjects on placebo and in 1 subject on reboxetine.

Conclusions

—

Selective NET blockade creates a phenotype that resembles idiopathic orthostatic intolerance. This observation supports the hypothesis that disordered norepinephrine uptake mechanisms can contribute to human cardiovascular disease. Our study also suggests that NET inhibition might be useful in preventing vasovagal reactions.
Traditional Risk Factors and the Incidence of Sudden Coronary Death With and Without Coronary Thrombosis in Blacks
Authors: Burke Allen P. , Farb Andrew , Pestaner Joseph , Malcom Gray T. , Zieske Arthur , Kutys Robert , Smialek John , Virmani Renu
Published: July 2002

Background
—

Blacks have a high rate of sudden coronary death (SCD). We determined the rate of SCD in men and women 30 to 69 years of age in a 6-year period recorded at a state Medical Examiner’s Office.

Methods and Results
—

In a subset of 327 whites and 130 blacks, hearts were systematically studied to determine the extent of coronary disease, presence and type of thrombus (acute rupture, acute erosion, stable plaque), and heart weight. These parameters were correlated with the presence of conventional risk factors. The estimated rate of SCD in blacks was similar to that in whites under the age of 40 years but increased compared with whites with advancing age, becoming 1.5 times the rate for whites in the 7th decade (95% of the increase in the 6th decade was due to sudden death with stable plaque). Among the autopsied group with severe coronary atherosclerosis, HDL cholesterol was higher and hypertension more prevalent in blacks, but there was no difference in the prevalence of healed infarcts, plaque burden, heart weight, acute thrombi, or rates of diabetes, cigarette smoking, and total cholesterol.

Conclusions
—

When compared with a control autopsy group of 568 deaths, multivariate analysis showed a significant association in blacks between stable plaque and left ventricular hypertrophy (risk ratio, 7.6), type 1 diabetes (risk ratio, 3.6), hypertension (risk ratio, 3.5), elevated total cholesterol (risk ratio, 3.1) and type 2 diabetes (risk ratio, 2.9). Because these risk factors are associated with SCD in blacks, they may be important targets for reducing the disparately high rate of SCD in blacks as compared with whites.
Importance of Continuous Chest Compressions During Cardiopulmonary Resuscitation
Authors: Kern Karl B. , Hilwig Ronald W. , Berg Robert A. , Sanders Arthur B. , Ewy Gordon A.
Published: July 2002

Background

—

Interruptions to chest compression–generated blood flow during cardiopulmonary resuscitation (CPR) are detrimental. Data show that such interruptions for mouth-to-mouth ventilation require a period of “rebuilding” of coronary perfusion pressure to obtain the level achieved before the interruption. Whether such hemodynamic compromise from pausing to ventilate is enough to affect outcome is unknown.

Methods and Results

—

Thirty swine (weight 35±2 kg) underwent 3 minutes of untreated ventricular fibrillation before 12 minutes of basic life support CPR. Animals were randomized to receive either standard airway (A), breathing (B), and compression (C) CPR with expired-gas ventilation in a 15:2 compression-to-ventilation ratio or continuous chest compression CPR. Those randomized to the standard 15:2 group had no chest compressions for a period of 16 seconds each time the 2 ventilations were delivered. Defibrillation was attempted at 15 minutes of cardiac arrest. All resuscitated animals were supported in an intensive care environment for 1 hour, then in a maintenance facility for 24 hours. The primary end point of neurologically normal 24-hour survival was significantly better in the experimental group receiving continuous chest compression CPR (12 of 15 versus 2 of 15;
P
<0.0001).

Conclusions

—

Mouth-to-mouth ventilation performed by single layperson rescuers produces substantial interruptions in chest compression–supported circulation. Continuous chest compression CPR produces greater neurologically normal 24-hour survival than standard ABC CPR when performed in a clinically realistic fashion. Any technique that minimizes lengthy interruptions of chest compressions during the first 10 to 15 minutes of basic life support should be given serious consideration in future efforts to improve outcome results from cardiac arrest.