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Psoriasis is a chronic inflammatory skin disease associated with reactive oxygen species (ROS) increase and a higher risk of cardiovascular (CV) events. We previously showed that the miR-200 family (miR-200s) is induced by ROS, miR-200c being the most upregulated member responsible for apoptosis, senescence, ROS increase, and nitric oxide decrease, finally causing endothelial dysfunction. Moreover, circulating miR-200c increases in familial hypercholesterolemic children and in plaques and plasma of atherosclerotic patients, two pathologies associated with increased ROS. Given miR-200s’ role in endothelial dysfunction, ROS, and inflammation, we hypothesized that miR-200s were modulated in lesional skin (LS) and plasma of psoriatic patients (Pso) and that their levels correlated with some CV risk determinants at a subclinical level. All Pso had severe psoriasis, i.e., Psoriasis Area and Severity Index PASI>10, and one of the following: at least two systemic psoriasis treatments, age at onset<40 years, and disease duration>10 years. RNA was extracted from plasma (Pso, N=29; Ctrl, N=29) and from nonlesional skin (NLS) and LS of 6 Pso and 6 healthy subject skin (HS) biopsies. miR-200 levels were assayed by quantitative RT-PCR. We found that all miR-200s were increased in LS vs. NLS and miR-200c was the most expressed and upregulated in LS vs. HS. In addition, circulating miR-200c and miR-200a were upregulated in Pso vs. Ctrl. Further, miR-200c positively correlated with PASI, disease duration, left ventricular (LV) mass, LV relative wall thickness (RWT), and E/e′, a marker of diastolic dysfunction. Multiple regression analysis indicates a direct association between miR-200c and both RWT and LV mass. Circulating miR-200a correlated positively only with LV mass and arterial pressure augmentation index, a measure of stiffness, although the correlations were nearly significant (P=0.06). In conclusion, miR-200c is upregulated in LS and plasma of Pso, suggesting its role in ROS increase and inflammation associated with CV risk in psoriasis. more...

It has been previously shown that vascular endothelial growth factor (VEGF) plays a central role in promoting angiogenesis during wound repair and that healing-impaired diabetic mice show decreased VEGF expression levels. In order to investigate the potential benefits of gene therapy with growth factors on wound repair, a replication-deficient recombinant adenovirus vector carrying the human VEGF(165) gene (AdCMV.VEGF(165)) was topically applied on excisional wounds of streptozotocin-induced diabetic mice. Treatment with AdCMV.VEGF(165) significantly accelerated wound closure when compared with AdCMV.LacZ-treated, as well as saline-treated control mice, by promoting angiogenesis at the site of injury. Our findings suggest that AdCMV.VEGF(165) may be regarded as a therapeutic tool for the treatment of diabetic ulcers. more...

Background —After endovascular injury, smooth muscle cells (SMCs) may be exposed to hemodynamic shear stress (SS), and these forces modulate neointima accumulation. The effect of SS on SMC migration and invasion is unknown, and it was examined in the present study. Methods and Results —Bovine aortic SMCs were exposed to laminar SS of 12 dyne/cm 2 for 3 (SS3) or 15 (SS15) hours; control (C3 and C15) SMCs were kept under static conditions. Platelet-derived growth factor (PDGF)-BB–directed SMC migration and invasion were evaluated by a modified Boyden chamber assay with filters coated with either gelatin or reconstituted basement membrane proteins (Matrigel), respectively. SS15 inhibited both SMC migration and invasion ( P P Conclusions —SS inhibits SMC migration and invasion via diminished PDGF-Rβ expression. This effect of SS is associated with decreased MMP-2 secretion and MT-MMP downregulation. more...

The tumor suppressor gene p53 has inhibitory effects on cell growth and angiogenesis and induces apoptosis when overexpressed in melanoma and in a variety of tumor cells by adenovirus-mediated gene transfer. The invasive ability of tumor cells, facilitating local infiltration and metastasis, is related to matrix metalloproteinase levels. In melanoma, matrix metalloproteinase-2 and matrix metalloproteinase-9 have a prominent role in this process. The aim of this study was to evaluate whether wild-type p53 overexpression, obtained by a recombinant adenovirus vector (AdCMV.p53), affects cell invasiveness through modulation of matrix metalloproteinase-2 and matrix metalloproteinase-9. Two human melanoma cell lines were used in this study: the SK-MEL-110, carrying a mutated p53 gene, and the SK-MEL-147, carrying the wild-type p53 gene. SK-MEL-110 cells infected with AdCMV.p53 exhibited decreased invasion capability from day 1 after infection, compared with cells not infected or infected with the control vector AdCMV.Null. This reduced invasiveness was associated with decreased matrix metalloproteinase-2 levels in conditioned media whereas no changes were detected in matrix metalloproteinase-9 secreted levels. No modulation in matrix metalloproteinase-2 mRNA levels was detectable, however, after wild-type p53 gene transfer. Furthermore, protein expression of secreted tissue inhibitor of metalloproteinase-2 was not altered by AdCMV.p53 treatment. In contrast, in SK-MEL-147 cells, AdCMV.p53 did not affect cell invasiveness and levels of secreted matrix metalloproteinase-2. Gene transfer of wild-type p53 inhibited proliferation of both cell lines, showing that also SK-MEL-147 cells respond to wild-type p53 overexpression. This novel mechanism of action of wild-type p53 gene transfer may contribute to its antitumor effect by downregulating cell invasion and matrix metalloproteinase-2 secreted levels in mutated p53 human melanoma cell lines. more...

Transfer of the cDNA coding for angiogenic factors represents a novel and promising approach to induce therapeutic angiogenesis and enhance blood flow to ischemic tissues which cannot be revascularized otherwise. This review will focus on therapeutic angiogenesis based on gene transfer techniques for the treatment of myocardial and limb ischemia. The experimental studies demonstrating the angiogenic effect of recombinant growth factors in animal models and in humans, as well as the most promising methods for gene transfer, will be described. Further, gene transfer studies to induce therapeutic angiogenesis will be reviewed to identify critical questions that still need to be answered before gene therapy with angiogenic factors may be considered for routine clinical application. more...

AIMS: HMGB1 injection into the mouse heart, acutely after myocardial infarction (MI), improves left ventricular (LV) function and prevents remodeling. Here, we examined the effect of HMGB1 in chronically failing hearts. METHODS AND RESULTS: Adult C57 BL16 female mice underwent coronary artery ligation; three weeks later 200 ng HMGB1 or denatured HMGB1 (control) were injected in the peri-infarcted region of mouse failing hearts. Four weeks after treatment, both echocardiography and hemodynamics demonstrated a significant improvement in LV function in HMGB1-treated mice. Further, HMGB1-treated mice exhibited a ∼23% reduction in LV volume, a ∼48% increase in infarcted wall thickness and a ∼14% reduction in collagen deposition. HMGB1 induced cardiac regeneration and, within the infarcted region, it was found a ∼2-fold increase in c-kit⁺ cell number, a ∼13-fold increase in newly formed myocytes and a ∼2-fold increase in arteriole length density. HMGB1 also enhanced MMP2 and MMP9 activity and decreased TIMP-3 levels. Importantly, miR-206 expression 3 days after HMGB1 treatment was 4-5-fold higher than in control hearts and 20-25 fold higher that in sham operated hearts. HMGB1 ability to increase miR-206 was confirmed in vitro, in cardiac fibroblasts. TIMP3 was identified as a potential miR-206 target by TargetScan prediction analysis; further, in cultured cardiac fibroblasts, miR-206 gain- and loss-of-function studies and luciferase reporter assays showed that TIMP3 is a direct target of miR-206. CONCLUSIONS: HMGB1 injected into chronically failing hearts enhanced LV function and attenuated LV remodelling; these effects were associated with cardiac regeneration, increased collagenolytic activity, miR-206 overexpression and miR-206 -mediated inhibition of TIMP-3. more...

In diabetic patients and animal models of diabetes mellitus (DM), circulating endothelial progenitor cell (EPC) number is lower than in normoglycaemic conditions and EPC angiogenic properties are inhibited. Stromal cell derived factor-1 (SDF-1) plays a key role in bone marrow (BM) c-kit(+) stem cell mobilization into peripheral blood (PB), recruitment from PB into ischemic tissues and differentiation into endothelial cells. The aim of the present study was to examine the effect of DM in vivo and in vitro, on murine BM-derived c-kit(+) cells and on their response to SDF-1. Acute hindlimb ischemia was induced in streptozotocin-treated DM and control mice; circulating c-kit(+) cells exhibited a rapid increase followed by a return to control levels which was significantly faster in DM than in control mice. CXCR4 expression by BM c-kit(+) cells as well as SDF-1 protein levels in the plasma and in the skeletal muscle, both before and after the induction of ischemia, were similar between normoglycaemic and DM mice. However, BM-derived c-kit(+) cells from DM mice exhibited an impaired differentiation towards the endothelial phenotype in response to SDF-1; this effect was associated with diminished protein kinase phosphorylation. Interestingly, SDF-1 ability to induce differentiation of c-kit(+) cells from DM mice was restored when cells were cultured under normoglycaemic conditions whereas c-kit(+) cells from normoglycaemic mice failed to differentiate in response to SDF-1 when they were cultured in hyperglycaemic conditions. These results show that DM diminishes circulating c-kit(+) cell number following hindlimb ischemia and inhibits SDF-1-mediated AKT phosphorylation and differentiation towards the endothelial phenotype of BM-derived c-kit(+) cells. more...

The present study was aimed at identifying chronic heart failure (CHF) biomarkers from peripheral blood mononuclear cells (PBMCs) in patients with ischemic (ICM) and nonischemic dilated (NIDCM) cardiomyopathy. PBMC gene expression profiling was performed by Affymetrix in two patient groups, 1) ICM (n = 12) and 2) NIDCM (n = 12) New York Heart Association (NYHA) III/IV CHF patients, vs. 3) age- and sex-matched control subjects (n = 12). Extracted RNAs were then pooled and hybridized to a total of 11 microarrays. Gene ontology (GO) analysis separated gene profiling into functional classes. Prediction analysis of microarrays (PAM) and significance analysis of microarrays (SAM) were utilized in order to identify a molecular signature. Candidate markers were validated by quantitative real-time polymerase chain reaction. We identified a gene expression profiling that distinguished between CHF patients and control subjects. Interestingly, among the set of genes constituting the signature, chemokine receptor (CCR2, CX3CR1) and early growth response (EGR1, 2, 3) family members were found to be upregulated in CHF patients vs. control subjects and to be part of a gene network. Such findings were strengthened by the analysis of an additional 26 CHF patients (n = 14 ICM and n = 12 NIDCM), which yielded similar results. The present study represents the first large-scale gene expression analysis of CHF patient PBMCs that identified a molecular signature of CHF and putative biomarkers of CHF, i.e., chemokine receptor and EGR family members. Furthermore, EGR1 expression levels can discriminate between ICM and NIDCM CHF patients. Copyright © 2009 the American Physiological Society. more...

Background Modification of the fiber proteins in replication-deficient adenoviral (Ad) vectors through incorporation of specific receptor-binding motifs may represent a strategy to enhance their tissue targeting capabilities. Methods In this study, we compared an unmodified Ad (GV10) with two mutated vectors obtained by insertion of specific target sequences that redirect binding, either toward αV integrin (RGD) or heparan sulfate (UTV) cellular receptors, for reporter gene expression spatial distribution in the rabbit skeletal muscle. In a first series of experiments, injection volume was kept constant and activity of a lacZ transgene was evaluated 48 h after injection of the Ad vectors at different doses. In separate experiments, the effects of different volumes of injection at a constant dose of Ad vector were monitored. Results All vectors evaluated showed a significant increase in the number of lacZ-positive muscle segments, with increasing vector dose. However, in muscles treated with the UTV vector, fewer muscle fibers were β-gal-positive than in GV10 or RGD vector treated animals. In fact, total β-gal activity increased in a dose-dependent fashion in the GV10- and RGD-treated muscles, but not in the UTV-treated ones. Remarkably, in samples from UTV-treated animals, a volume-dependent enhancement of transgene expression was observed during experiments performed at the same dose and different injection volumes. Conclusions The results of the present study demonstrate that altering Ad affinity for cellular receptors modulates the level and distribution of transgene activity, conferring characteristics that may allow for treatment customization. Copyright © 2004 John Wiley & Sons, Ltd. more...

In recent years, new knowledge has been provided from the study of the biological mechanisms underlying the angiogenic process, i.e. the development of a new vasculature from preexisting blood vessels. These advances suggested a possible new approach for the therapy of peripheral obstructive arterial disease, based on the treatment of ischemic tissues with angiogenic growth factors. As demonstrated by experimental studies in animal models, a therapeutic effect can be reached as the newly formed vascular network, functioning as a biologic by-pass, restores a normal blood supply to the ischemic territories. New techniques of gene therapy proved effective in reaching sustained concentrations of angiogenic factors in the target tissues. This paper will briefly describe the methodological background, the results of the early clinical applications of angiogenic gene therapy and the open questions that need to be addressed before this new approach can be proposed as an effective option instead of existing medical and surgical therapies. more...

In patients with myotonic dystrophy, histopathological and electrophysiologic abnormalities of cardiac conduction system may lead to sudden cardiac death due to atrioventricular block or to ventricular electrical instability.Four members of a family affected by myotonic dystrophy are reported, which underwent a cardiological examination including invasive electrophysiological study and prolonged follow-up. Other 3 members of the same family had died suddenly. No clinical data are available for 2 of these patients, while paroxysmal atrial flutter and non sustained ventricular tachycardia had been detected at Holter in the third one.Signs of atrioventricular conduction impairment, poorly predictable with non invasive electrocardiography, were found in the 4 patients undergoing intracardiac electrophysiologic study. In 2/4 patients, both having dizzy spells and the most impaired atrioventricular conduction, a pace-maker was implanted. Polymorphic, non sustained ventricular response was induced in 2/4 patients, 1 of them with spontaneous high grade ventricular arrhythmias.The respective role of atrioventricular conduction impairment and ventricular vulnerability in determining sudden death has not been stated so far in these patients. The observed polymorphic non sustained response should not be "a priori" disregarded as aspecific, since it could be the electrophysiological counterpart of a peculiar anatomic arrhythmogenic substrate. A comprehensive study, including invasive electrophysiology, is advisable in all patients with myotonic dystrophy whenever a member of their family presents with cardiac involvement, to assess the most probable life-threatening arrhythmogenic mechanism. more...

Background Left ventricular remodeling after infarction is accompanied by dysfunction of regions adjacent to the infarct. We hypothesized that myocyte contractile abnormalities and elongation greater than in remote regions underlie adjacent-region dysfunction in the remodeled ventricle. The activation of the tyrosine kinase pathway, which mediates in vitro hypertrophy by stretch and/or angiotensin, was also assessed in myocytes separately isolated from adjacent and remote regions. Methods and Results ECG-gated magnetic resonance imaging short-axis images were acquired 2 weeks after coronary ligation in rats. After the rats were killed, myocytes were isolated from animals with large (n=7) and small (n=7) infarcts and from 4 sham-operated controls. Regional wall thickening was correlated with local myocyte function and morphology. Cytochemistry for tyrosine-phosphorylated proteins was performed in myocytes from the same regions. Remodeled ventricles were dilated relative to controls by 93.7%, and wall thickening in adjacent regions was less than in remote regions (27.8±6.11% versus 54.0±10.1%, P P P r =.72, P P P Conclusions After infarction, impaired wall thickening in adjacent regions is accompanied by greater myocyte dysfunction and elongation than in remote regions. These abnormalities are associated with regional differences in the tyrosine kinase pathway activation, indicating a potential intracellular mechanism for postinfarct myocardial remodeling. more...

Although angiotensin-converting enzyme inhibitors have been shown to affect left ventricular (LV) remodeling favorably in several conditions, it remains unclear whether they can influence LV geometric pattern in hypertension. To address this issue, 122 patients (71 men and 51 women; mean age = 51 +/- 10 years) with mild to moderate hypertension were studied prospectively. All underwent clinical evaluation and Doppler echocardiography at entry and more than 2 years of quinapril therapy (10-40 mg/day). According to either LV mass (normal if < 131 g/m2 for men or < 100 g/m2 for women) or the ratio of LV posterior wall thickness to diastolic diameter (RWT; normal if < 0.45) at baseline, 58 patients had normal mass and RWT, 18 patients had concentric remodelling (i.e., normal mass but increased RWT), 24 patients had eccentric hypertrophy (i.e., increased mass but normal RWT), and 22 patients had concentric hypertrophy (i.e., increase in both mass and RWT). After 6 months of quinapril therapy, all patients with normal left ventricles showed the maintenance of mass and RWT within normal limits. Patients with concentric remodeling showed no increase in mass but had a significant decrease in RWT. Patients with eccentric hypertrophy exhibited a significant reduction in mass with no substantial change in RWT. Patients with concentric hypertrophy had a significant reduction in both mass and RWT. Changes in LV mass and geometry were maintained during the 2-year period of treatment and were paralleled by improvements in Doppler indices of LV diastolic function in each group. It is concluded that quinapril, with its well-known effects on LV hypertrophy, modifies the LV geometric pattern of hypertensive patients favorably, regardless of the presence of an abnormal LV mass or RWT. more...

Intracellular signaling pathways activated by both PDGF and basic fibroblast growth factor (bFGF) have been implicated in the migration of vascular smooth muscle cells (VSMC), a key step in the pathogenesis of many vascular diseases. We demonstrate here that, while bFGF is a weak chemoattractant for VSMCs, it is required for the PDGF-directed migration of VSMCs and the activation of calcium/calmodulin-dependent protein kinase II (CamKinase II), an intracellular event that we have previously shown to be important in the regulation of VSMC migration. Neutralizing antibodies to bFGF caused a dramatic reduction in the size of the intracellular calcium transient normally seen after PDGF stimulation and inhibited both PDGF-directed VSMC migration and CamKinase II activation. Partially restoring the calcium transient with ionomycin restored migration and CamKinase II activation as did the forced expression of a mutant CamKinase II that had been "locked" in the active state by site-directed mutagenesis. These results suggest that bFGF links PDGF receptor stimulation to changes in intracellular calcium and CamKinase II activation, reinforcing the central role played by CamKinase II in regulating VSMC migration. more...

Wall thickening (WT) is impaired in non-infarcted regions adjacent to Myocardial Infarction (MI) and is thought to be caused by mechanical overload and geometric chamber distortion. The contribution of abnormalities intrinsic to the myocyte to impaired WT during remodeling has not been examined. To correlate local WT in vivo with myocyte morphology and function during LV remodeling, magnetic resonance imaging (MRI) was performed 2 weeks after MI (left coronary artery ligation) by obtaining EKG-gated spin-echo shortaxis images (1.5 Tesla, 3 inch coil). Myocytes were isolated from 14 rats with MI and 4 shams. Local WT in regions adjacent (A) and remote (R) to the infarct scar visible by MRI was correlated with cell morphology and function, studied in myocytes isolated from A and R. MI size measured by planimetry ranged from 5% to 30% (mean 18.7%) of the outer LV area. Regional differences in local WT were present in MI hearts: average %WT in A was lower than in R (27.8 ± 6.14 (sem) vs 54.0 ± 10.17: p l 0.01). In rats with large MI (MI g 20%, n = 7). cells were longer than in sham (p l 0.05: n = 175) both in R(143.1 ± 1.76 vs 120.9 ± 2.40 μm) and in A (150.3 ± 1.89 vs 122.6 ± 2.02 μm) while no changes were evidenced in cell width. Cells from A were longer than those from R(p l 0.05). A positive correlation between MI size and cell length was found (for A: r = 0.8, slope 0.07). Electrically-stimulated cell contraction (see figure, %ES: cell shortening / diastolic length: values aTe mean ± sem), was impaired in A with respect to sham (**: p l 0.05) and to R (*: p = 0.06). Thus, during post-MI remodeling, dysfunction in A non-infarcted regions is associated with greater myocyte elongation and dysfunction than in R. In conclusion, local myocyte dysfunction contributes to WT impairment in adjacent regions after MI. Download : Download high-res image (33KB) Download : Download full-size image more...

Background Several cytokines are associated with the development and/or progression of chronic heart failure (CHF). Our aim was to look more closely at the cytokine networks involved in CHF, and to assess whether disease etiology affects cytokine expression. The study population was comprised of a) 69 patients with stable CHF, New York Heart Association (NYHA) II/IV classes, secondary to ischaemic (ICM) and non ischaemic dilated (NIDCM) cardiomyopathy and b) 16 control subjects. We analyzed and compared the plasma levels of 27 pro- and anti-inflammatory mediators, in the study population and assessed for any possible correlation with echocardiographic parameters and disease duration. Methods 27 cytokines and growth factors were analyzed in the plasma of ICM- (n = 42) and NIDCM (n = 27) NYHA class II-IV patients vs age- and gender-matched controls (n = 16) by a beadbased multiplex immunoassay. Statistical analysis was performed by ANOVA followed by Tukey post-hoc test for multiple comparison. Results Macrophage inflammatory protein (MIP)-1β, Vascular endothelial growth factor (VEGF), interleukin (IL)-9, Monocyte chemotactic protein (MCP)-1, and IL-8 plasma levels were increased in both ICM and NIDCM groups vs controls. In contrast, IL-7, IL-5, and Interferon (IFN)-γ were decreased in both ICM and NIDCM groups as compared to controls. Plasma IL-6 and IL-1 β were increased in ICM and decreased in NIDCM, vs controls, respectively. IL-9 levels inversely correlated, in ICM patients, with left ventricular ejection fraction (LVEF) while IL-5 plasma levels inversely correlated with disease duration, in NYHA III/IV ICM patients. This is the first time that both an increase of plasma IL-9, and a decrease of plasma IL-5, IL-7 and IFN-γ have been reported in ICM as well as in NIDCM groups, vs controls. Interestingly, such cytokines are part of a network of genes whose expression levels change during chronic heart failure. The altered expression levels of MIP-1 β, VEGF, MCP-1, IL-1 β, IL-6, and IL-8, found in this study, are in keeping with previous reports. Conclusions The increase of plasma IL-9, and the decrease of plasma IL-5, IL-7 and IFN-γ in ICM as well as in NIDCM groups vs controls may contribute to get further insights into the inflammatory pathways involved in CHF. more...

Three cases are reported, in whom MCG mapping, performed during sustained reentry tachycardias, was successful in localizing respectively the atrial insertion of a right-sided Kent bundle (case n° 1), the ventricular insertion of a nodo-ventricular (Mahaim) accessory pathway (case n° 2) and reentry within the atrio ventricular node (case n° 3). more...

Since the introduction, in 1982, of a Biomagnetic facility in the clinical environment, efforts were concentrated to investigate whether magnetocardiography could really provide new information of potential diagnostic use, even avoiding electromagnetic shielding to facilitate simultaneous biomagnetic and conventional cardiac investigations, including cardiac catheterization for invasive electrophysiological procedures. More than 350 patients have been magnetically investigated using a single-channel second-order gradiometer. Results of 281 MCG studies, whose data have been extensively analyzed with updated software programs, are reported. Magnetocardiographic (MCG) mapping during endocardial pacing was performed to quantify the accuracy of MCG localization of intracardiac dipolar sources. MCG classification of ventricular preexcitation has been attempted in 70 patients with overt preexcitation. MCG localization of the ventricular preexcited area was accurate and reproducible, provided that during mapping a sufficient degree of ventricular preexcitation was present. MCG mapping during orthodromic A-V re-entry tachycardia has been also employed to attempt the localization of retrograde atrial preexcitation as well as the site of origin of atrial and ventricular tachyarrhythmias. For validation, the results of catheter and epicardial mappings have been used. Other applications of clinical magnetocardiography are under evaluation. The use of the Relative smoothness index needs, in our opinion, a larger experience to define its reliability as a predictor of risk for sudden death. MCG follow-up study of patients with transplanted hearts seems to be a promising application, for early detection of acute graft rejection reaction. Our reported case strongly supports this potentiality. Present work is also addressed to develop an integrated system allowing easy MCG mapping during cardiac catheterization, as a new method to guide diagnostic and therapeutic procedures as close as possible to the arrhythmogenic substrate. more...

Magnetocardiography, that is to say the recording of the magnetic field generated by the electrical activity of the heart, was born in 1963 when Baule and McFee, using an induction coil, measured for the first time magnetic signals produced by a human heart [2]. Since then, the evolution from a pioneering experimental observation to the present state of art has passed through fundamental technological progress. First, in 1970, the introduction of superconducting instrumentation in the MIT shielded room demonstrated that magnetocardiograms of quality comparable with that of standard electrocardiograms could be recorded [6, 8, 36]. The next important step was the adoption of gradiometric detection coils which allowed MCG recording in unshielded laboratories [1, 3, 33,44, 47] and opened the way to pioneering clinical measurements [4, 16, 18]. During the same years MCG were also recorded without a superconducting instrumentation [9]. Since the beginning the question arose whether or not magnetic measurements could increase the diagnostic capability of cardiologists in respect to more conventional methods. Several different approaches were used to quantify the information [5, 8, 33, 39] and, although some authors still favour analysis of MCG signal in the time domain both at standard [7, 28, 49] as well as at high resolution [38] isofield contour maps are nowadays preferred to give images of the magnetic field distribution during depolarization and repolarization [10, 11, 13, 21, 22, 27, 29]. more...

First MCG recording in one patient with WPW was reported by Erne’ and Fenici (1984). Since then several preliminary measurements have been published (Fenici et al 1985–88; Katila et al 1988; Novak el al 1988; Oeff et al 1989), demonstrating the accuracy of MCG to localize Kent type accessory pathways. Here we report present results of our ongoing perspective study carried out to interprete the MCG patterns and to compare the respective localization power of electrocardiographic and magnetocardiographic criteria. more...

At the beginning of the eighties still no demonstration had been given that magnetocardiography could be performed in a noisy unshielded hospital environment. Furthermore, when the first so called “high resolution MCG measurements” were reported (Farrel et a1 1978; Fenici et a1 1980 ), their interpretation and potential diagnostic utility were questionable. Tentative interpretation and validation of the experimental measurements on the basis of mathematical models (Leoni et a1 1982; Erne’ et a1 1985; Lorenzana et a1 1985), although clearcut and impressively coherent with what expected from the anatomy and physiology of the heart, were strongly criticized. Few experimental animal investigation had given counterdicting results (Leifer et a1 1983). Both cardiac electrophysiologists and cardiologists asked for direct demonstration that magnetocardiography could really provide new information with respect to the less expensive and troubleless electric measurements and that the MCG could be easily recorded in an hospital setting. For this reason at the Clinical Physiology Laboratory of the Catholic University of Rome a perspective project was started in 1980 to set up a Cardiovascular Biomagnetism Unit in the hospital, which should feature both the characteristics of a Biomagnetism and Cardiac Catheterization laboratory, without the use of any electromagnetic shielding. more...

Magnetocardiographic mapping during cardiac endocardia1 pacing was initially attempted by us, in patients undergoing invasive electrophysiological study for clinical reasons, in order to ascertain the reliability of the biomagnetic method in localizing a dipolar source placed in the human heart (Fenici et a1 1985,1986a,b,c). Subsequently similar results have been reported, with measurements carried out in two patients with permanently implanted pacemakers (Schmitz 1988) and in animals (Costa Monteiro et a1 1987). Here we report present results of an ongoing systematic research, carried out in our catheterization laboratory to quantify the accuracy of MCG localization of a catheter pacing different sites of the heart. more...

Magnetic localization of the site of onset of cardiac arrhythmias both of atrial and ventricular origin was first reported in 1986 (Fenici et al, 1987–89). However the accuracy of such localization procedures had not been validated so far. In this paper the reproducibility of such measurements is reported in several patients. Moreover the validation of magnetic localisation of ventricular tachycardia with conventional invasive endocardial mapping is described in one patient with previous myocardial infarction (MI). more...

Abstract —Endothelial cells are exposed to an acidotic environment in a variety of pathological and physiological conditions. However, the effect of acidosis on endothelial cell function is still largely unknown, and it was evaluated in the present study. Bovine aortic endothelial cells (BAECs) were grown in bicarbonate buffer equilibrated either with 20% CO 2 (pH 7.0, acidosis) or 5% CO 2 (pH 7.4, control). Acidosis inhibited BAEC proliferation in 10% FCS, whereas by day 7 in serum-free medium, cell number was 3-fold higher in acidotic cells than in control cells. Serum deprivation enhanced BAEC apoptosis, and apoptotic cell death was markedly inhibited by acidosis. Additionally, acidosis inhibited FCS-stimulated migration in a modified Boyden chamber assay and FCS-stimulated differentiation into capillary-like structures on reconstituted basement membrane proteins. Conditioned media from BAECs cultured for 48 hours either at pH 7.0 or pH 7.4 enhanced BAEC proliferation and migration at pH 7.4, and both effects were more marked with conditioned medium from BAECs grown in acidotic than in control conditions. Acidosis enhanced vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) mRNA expression as well as bFGF secretion, and a blocking bFGF antibody inhibited enhanced BAEC migration in response to conditioned medium from acidotic cells. These results show that acidosis protects endothelial cells from apoptosis and inhibits their proangiogenic behavior despite enhanced VEGF and bFGF mRNA expression and bFGF secretion. more...

A new protocol is described for non-invasive evaluation of electrophysiological effects of autonomic nervous system on both normal and abnormal atrio-ventricular conduction in patients with Wolff-Parkinson-White (WPW) syndrome. In 64 WPW patients with stable Kent-type ventricular preexcitation transoesophageal atrial pacing has been carried out to quantify changes in both atrioventricular (AV) node and Kent bundle refractoriness and maximal conductive capability induced by posture, physical exercise and psychophysiological activation. A significant shortening of AV nodal and accessory pathway refractory periods was found, induced by manoeuvres enhancing the sympathetic outflow, being the AV node the most sensitive structure. This finding suggests that an exhaustive investigation protocol of WPW patients should include the evaluation of the neurovegetative effects on cardiac electrophysiological parameters, under conditions which can reproduce as close as possible the individual situations a patient has to face in his real life. more...