Publications by authors named "Hugo A Garro"

24 Publications

  • Page 1 of 1

Verbascoside, synthetic derivatives and other glycosides from Argentinian native plant species as potential antitumoral agents.

Nat Prod Res 2020 Jan 10:1-6. Epub 2020 Jan 10.

Área de Química Orgánica, INTEQUI-CONICET-UNSL, San Luis, Argentina.

A phytochemical study was performed on three native plant species from the central-western zone of Argentina: Grisebach Torr. & A. Gray and L. We could obtain verbascoside () from . From , we could obtain 1, 5, 9--deoxyloganic acid () L. Finally, we could isolate 2--(-rhamnopyranosyl)-3-angeloyloxy-15-acetyloxy-7,13(14)--dien--labdane () and 2--(-rhamnopyranosyl)-3--angeloyloxy-15-hydroxy-7,13(14)--dien--labdane () from . Moreover, three derivatives from , and one semi-synthetic derivative from , were prepared. PCR reaction was used to analyse the activity against DNA polymerase and cell culture to determine cytotoxicity and antitumoral activity. Verbascoside ( was strongly active in the nanomolar scale (IC = 356 nM) against DNA polymerization. Moreover, verbascoside was also strongly active in the nanomolar scale against human melanoma cell line (IC = 256 nM) and human colorectal cell line (IC = 320 nM). Furthermore, derivatives and were cytotoxic against both cancer cell lines.
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http://dx.doi.org/10.1080/14786419.2019.1710701DOI Listing
January 2020

Metal coordination and peripheral substitution modulate the activity of cyclic tetrapyrroles on αS aggregation: a structural and cell-based study.

J Biol Inorg Chem 2019 12 5;24(8):1269-1278. Epub 2019 Sep 5.

Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK, Rosario, Argentina.

The discovery of aggregation inhibitors and the elucidation of their mechanism of action are key in the quest to mitigate the toxic consequences of amyloid formation. We have previously characterized the antiamyloidogenic mechanism of action of sodium phtalocyanine tetrasulfonate ([Na(HPcTS)]) on α-Synuclein (αS), demonstrating that specific aromatic interactions are fundamental for the inhibition of amyloid assembly. Here we studied the influence that metal preferential affinity and peripheral substituents may have on the activity of tetrapyrrolic compounds on αS aggregation. For the first time, our laboratory has extended the studies in the field of the bioinorganic chemistry and biophysics to cellular biology, using a well-established cell-based model to study αS aggregation. The interaction scenario described in our work revealed that both N- and C-terminal regions of αS represent binding interfaces for the studied compounds, a behavior that is mainly driven by the presence of negatively or positively charged substituents located at the periphery of the macrocycle. Binding modes of the tetrapyrrole ligands to αS are determined by the planarity and hydrophobicity of the aromatic ring system in the tetrapyrrolic molecule and/or the preferential affinity of the metal ion conjugated at the center of the macrocyclic ring. The different capability of phthalocyanines and meso-tetra (N-methyl-4-pyridyl) porphine tetrachloride ([HPrTPCl]) to modulate αS aggregation in vitro was reproduced in cell-based models of αS aggregation, demonstrating unequivocally that the modulation exerted by these compounds on amyloid assembly is a direct consequence of their interaction with the target protein.
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http://dx.doi.org/10.1007/s00775-019-01711-zDOI Listing
December 2019

Interaction of Cu(i) with the Met-X-Met motif of alpha-synuclein: binding ligands, affinity and structural features.

Metallomics 2018 10;10(10):1383-1389

Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR, UNR-MPIbpC) and Instituto de Investigaciones para el Descubrimiento de Fármacos de Rosario (IIDEFAR, UNR-CONICET), Universidad Nacional de Rosario, Ocampo y Esmeralda, S2002LRK Rosario, Argentina.

The identity of the Cu(i) binding ligands at Met-X3-Met site of AcαS and its role into the affinity and structural properties of the interaction were elucidated by NMR spectroscopy. We provide evidence that the source of ligands for Cu(i) binding to the Met-X3-Met site comes from the N-terminal acetyl group and the Met-1, Asp-2 and Met-5 residues. From the study of site-directed mutants and synthetic peptide models of αS we demonstrated the critical role played by Met-1 and Met-5 residues on the binding affinity of the Cu(i) complex, acting as the main metal anchoring residues. While having a more modest impact in the affinity features of Cu(i) binding, as compared to the Met residues, the N-terminal acetyl group and Asp-2 are important in promoting local helical conformations, contributing to the stabilization of these structures by favoring Cu(i) binding.
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http://dx.doi.org/10.1039/c8mt00232kDOI Listing
October 2018

DNA Related Enzymes as Molecular Targets for Antiviral and Antitumoral Chemotherapy. A Natural Overview of the Current Perspectives.

Curr Drug Targets 2019 ;20(1):70-80

Intequi-Conicet, Fac. Qca., Bioqca. y Fcia., Univ. Nac. de San Luis (U.N.S.L), Chacabuco y Pedernera, 5700 San Luis, Argentina.

Background: The discovery of new chemotherapeutic agents still remains a continuous goal to achieve. DNA polymerases and topoisomerases act in nucleic acids metabolism modulating different processes like replication, mitosis, damage repair, DNA topology and transcription. It has been widely documented that Polymerases serve as molecular targets for antiviral and antitumoral chemotherapy. Furthermore, telomerase is a ribonucleoprotein with exacerbated activity in most of the tumor cell lines, becoming as an emergent target in Cancer treatment.

Methods: We undertook an exhaustive search of bibliographic databases for peer-reviewed research literature related to the last decade. The characteristics of screened bibliography describe structure activity relationships and show the principal moieties involved. This work tries to summarize the investigation about natural and semi-synthetic products with natural origin with the faculty to inhibit key enzymes that play a crucial role in DNA metabolism.

Results: Eighty-five data references were included in this review, showing natural products widely distributed throughout the plant kingdom and their bioactive properties such as tumor growing inhibitory effects, and anti-AIDS activity.

Conclusion: The findings of this review confirm the importance to find new drugs and biologically active natural products, and their potential medicinally useful benefits.
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http://dx.doi.org/10.2174/1389450119666180426103558DOI Listing
February 2020

Masquerading bundle branch block obscuring the diagnosis of Brugada syndrome: an electrocardiographic and vectorcardiographic study.

Clin Case Rep 2017 08 11;5(8):1362-1368. Epub 2017 Jul 11.

Division of Cardiology Ramos Mejía Hospital Buenos Aires Argentina.

We describe the induction of a masquerading bundle branch block in two patients with Brugada syndrome following the administration of Ajmaline. The development of this conduction disturbance prevented the correct electrocardiographic diagnosis. However, the simultaneously obtained vectocardiogram identified both the Brugada pattern and the masquerading bundle branch block.
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http://dx.doi.org/10.1002/ccr3.1059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5538077PMC
August 2017

Cytotoxic and Antitumor Activity of some Coumarin Derivatives.

Nat Prod Commun 2016 Sep;11(9):1289-1292

Several natural and synthetic coumarins were assayed against different cancer cell lines. Four of them have shown cytotoxicity against a panel of three human solid tumor cell lines (HeLa, T-47D, and WiDr) and a clearly activity/hydrophobicity relationship. Compound 13 proved to be the most active product in all cell lines tested, with values of 8.0 (±0.38) μM against HeLa cells and also able to inhibit Taq DNA polymerase. This dual activity of 13 makes it a candidate to be considered as a "lead" compound in the search for novel antitumor drugs.
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September 2016

Intraventricular aberrancy, pseudo-supernormality and intrahisian conduction "gap" in premature junctional beats.

Int J Cardiol 2015 Dec 28;201:490-2. Epub 2014 Sep 28.

Division of Cardiology, Hospital Ramos Mejia, Buenos Aires, Argentina. Electronic address:

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http://dx.doi.org/10.1016/j.ijcard.2014.09.093DOI Listing
December 2015

Coumarins as Potential Inhibitors of DNA Polymerases and Reverse Transcriptases. Searching New Antiretroviral and Antitumoral Drugs.

Curr Drug Discov Technol 2015 ;12(2):66-79

Department of Chemistry, Faculty of Chemistry, Biochemistry and Pharmacy. University of San Luis, P.O. 5700, San Luis, Argentine.

Human Immunodeficiency Virus (HIV) is the viral agent of Acquired Immunodeficiency Syndrome (AIDS), and at present, there is no effective vaccine against HIV. Reverse Transcriptase (RT) is an essential enzyme for retroviral replication, such as HIV as well as for other RNA infectious viruses like Human T lymphocyte virus. Polymerases act in DNA metabolism, modulating different processes like mitosis, damage repair, transcription and replication. It has been widely documented that DNA Polymerases and Reverse Transcriptases serve as molecular targets for antiviral and antitumoral chemotherapy. Coumarins are oxygen heterocycles that are widely distributed throughout the plant kingdom. Natural coumarins have attraction due to their bioactive properties such as tumor promotion inhibitory effects, and anti-HIV activity. Coumarins and derivates exhibit potent inhibitory effects on HIV-1 replication in lymphocytes and compounds isolated from Calophyllum inophyllum or DCK derivates showed inhibitory activity against human RT. Furthermore, natural isocoumarins isolated from cultures of fungi or hydroxycoumarins were able to inhibit human DNA polymerase. In view of their importance as drugs and biologically active natural products, and their medicinally useful properties, extensive studies have been carried out on the synthesis of coumarin compounds in recent years. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), a class of antiretroviral chemotherapeutic agents, act by binding to an allosteric pocket showing, generally, low toxicity. This work tries to summarize the investigation about natural and synthetic coumarins with the ability to inhibit key enzymes that play a crucial role in DNA metabolism and their possible application as antiretroviral and antitumoral agents.
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http://dx.doi.org/10.2174/1570163812666150716111719DOI Listing
May 2016

The mechanisms of spontaneous termination of reentrant supraventricular tachycardias.

Int J Cardiol 2015 Jul 1;191:151-8. Epub 2015 May 1.

National Academy of Medicine, Buenos Aires, Argentina.

Background: Atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) often terminate spontaneously, presumably due to changes in the electrophysiological properties of the reentrant circuit. However, the mechanism of spontaneous termination of these arrhythmias is incompletely understood.

Methods: We included 70 consecutive patients with reentrant supraventricular tachycardias (35 AVNRT, 35 AVRT) in whom the arrhythmia ended spontaneously during the electrophysiologic study. We determined in each patient the duration of the induced arrhythmia, site of block, beat-to-beat oscillations in tachycardia cycle-length (CL), A-H, H-V, H-A and V-A intervals.

Results: In 21/34 (62%) patients with AVNRT and 19/30 (63%) with orthodromic AVRT, tachycardia termination was preceded by progressive increase in tachycardia CL due to prolongation of the A-H interval (Mobitz type-I pattern). In 13/34 patients with AVNRT (38%) and 11/30 with orthodromic AVRT (37%), termination occurred suddenly without a preceding change in CL, with block ensuing retrogradely either in the fast AV nodal pathway or the accessory pathway (Mobitz type-II pattern). In 4/5 patients with antidromic AVRT the tachycardia ended at the retrograde limb with previous prolongation of the VA interval.

Conclusion: Spontaneous termination of AVNRT and AVRT is a time-related phenomenon. Despite different pathways being involved in these two reentrant tachycardias, termination can follow antegrade or retrograde block in similar ratio (60% antegradely and 40% retrogradely). Antegrade block is preceded by prolongation of the AH interval (Mobitz type-I), whereas retrograde block occurs unexpectedly in the retrograde limb (Mobitz type-II). Fatigue of conduction appears to be involved in this phenomenon.
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http://dx.doi.org/10.1016/j.ijcard.2015.04.239DOI Listing
July 2015

A new iridoid, verbascoside and derivatives with inhibitory activity against Taq DNA polymerase.

Bioorg Med Chem Lett 2015 Feb 23;25(4):914-8. Epub 2014 Dec 23.

INTEQUI-CONICET, Fac. Qca., Bioqca. y Fcia., Univ. Nac. de San Luis (U.N.S.L), Chacabuco y Pedernera, 5700 San Luis, Argentina. Electronic address:

DNA polymerases are enzymes that play a crucial role in DNA metabolism such as replication, repair, transcription, recombination, and chromosome segregation during mitosis. Herein we report the isolation of a new iridoid (6-epi-catalpol, 2) and per-O-acetyl-verbascoside (11) from aerial part of Buddleja cordobensis Grisebach (Buddlejaceae). From compound 2, we have obtained eight compounds by chemical transformation. This group of compounds at a concentration of 500μM was assayed against Taq DNA polymerase. Compound 11 (per-O-acetyl-verbascoside) was the most active with an IC50 of 1.21±0.18μM; compounds 9, 2 and 8 were strong inhibitors with IC50 values of 5.57±0.70, 21.62±0.22 and 78.13±0.93μM, respectively. Compounds 11 and 9 could be a leader structures to development new anticancer chemotherapy medicines and a useful tool to investigate DNA polymerase activity.
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http://dx.doi.org/10.1016/j.bmcl.2014.12.052DOI Listing
February 2015

Chemistry and biological activity of coumarins at molecular level.

Nat Prod Commun 2014 Aug;9(8):1091-4

Synthetic coumarins were prepared in high yields using ionic liquids as an environmental friendly alternative. 3,4-Dimethyl-7-hydroxycoumarin (3ab) and 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (3bc) showed interesting activity against Taq DNA polymerase with IC50 values of 115.7 microM and 82.2 microM, respectively. Also, 4-methyl-7-hydroxycoumarin (3aa) and 4-methyl-5,7-dihydroxycoumarin (3ba) exhibited inhibitory activity against MMLV-RT with IC50 values of 23.5 microM and 18.3 microM, respectively. These inhibitors could have importance as antiretroviral chemotherapeutic agents and also for the development of antitumor drugs.
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August 2014

The multiple electrocardiographic manifestations of ventricular repolarization memory.

Curr Cardiol Rev 2014 Aug;10(3):190-201

Centro de Arritmias Cardíacas de la Ciudad Autónoma de Buenos Aires. Cardiology Division. Hospital J.M. Ramos Mejía. Buenos Aires. Argentina.

T wave "memory" is a peculiar variety of cardiac remodeling caused by a transient change in the course of ventricular depolarization (due to ventricular pacing, rate-dependent intraventricular block, ventricular preexcitation or tachyarrhythmias with wide QRS complexes). It is usually manifested by inverted T waves that appears when normal ventricular activation is restored. This phenomenon is cumulative and occurs earlier if the ventricular myocardium has previously been exposed to the same conditioning stimuli. In this article the different conditions giving rise to "classical" T wave memory development are reviewed and also "another" type of T wave memory is described. It is also shown that cardiac memory may induce not only negative (pseudo-primary) T waves but also a reversal of primary and pseudoprimary T waves leading to "normalization" of ventricular repolarization. The knowledge of these dissimilar consequences of T wave memory is essential to assess the characteristics of ventricular repolarization.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4040871PMC
http://dx.doi.org/10.2174/1573403x10666140514102021DOI Listing
August 2014

Clinical evaluation of losartan and diltiazem on the development of T-wave memory by right apical ventricular pacing.

J Am Coll Cardiol 2014 May 5;63(18):1929-31. Epub 2014 Mar 5.

Centro de Arritmias Cardíacas de la Ciudad Autónoma de Buenos Aires, División Cardiología, Hospital J.M. Ramos Mejía, Buenos Aires, Argentina.

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http://dx.doi.org/10.1016/j.jacc.2014.02.524DOI Listing
May 2014

[A simple AV block?].

Medicina (B Aires) 2013 ;73(4):337

Centro de Arritmias Cardíacas de la Ciudad de Buenos Aires, Buenos Aires, Argentina.

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June 2014

A shifting heart shifts the transition index.

Europace 2014 Jan 12;16(1):70. Epub 2013 Jun 12.

Heart Rhythm Service, Queen's University, Kingston, Ontario, Canada K7L 2V7.

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http://dx.doi.org/10.1093/europace/eut146DOI Listing
January 2014

A reappraisal on lidocaine-sensitive repetitive, uniform atrial tachycardia.

Ann Noninvasive Electrocardiol 2013 Jan 22;18(1):1-11. Epub 2012 Nov 22.

Centro de Arritmias Cardíacas de la Ciudad de Buenos Aires, Division of Cardiology, Hospital J. M. Ramos Mejía, and Pontificia Universidad Católica Argentina Santa María de los Buenos Aires, Buenos Aires, Argentina.

Background: Lidocaine sensitive, repetitive atrial tachycardia is an unusual arrhythmia whose electrophysiologic substrate remains undefined. We aimed to analyze the electropharmacologic characteristics of this arrhythmia with emphasis on its cellular substrate and response to drug challenges.

Methods: We retrospectively analyzed a series of 18 patients from an electrocardiographic and electrophysiologic perspective and the response to pharmacological challenge.

Results: There was no evidence of structural heart disease in 12 patients, 4 patients presented with systemic hypertension; one patient had a prior myocardial infarction and one a mitral valve prolapse. The arrhythmia depicted a consistent pattern in nine patients. The first initiating ectopic beat showed a long coupling interval, the cycle length of the second atrial ectopic beat presented the shortest cycle length and a further prolongation was apparent towards the end of the atrial salvos. Conversely, in the other nine cases, the atrial tachycardia cycle length was erratic. The arrhythmia was suppressed by asynchronous atrial pacing at cycle lengths longer than those of the atrial tachycardia. Intravenous lidocaine eliminated the arrhythmia in all patients, but intravenous verapamil suppressed the atrial tachycardia in only two patients while adenosine caused a transient disappearance in 2/8 patients. Only one patient responded to all the three agents. Radiofrequency ablation was successfully performed in 10 patients.

Conclusions: Repetitive uniform atrial tachycardia can be sensitive to lidocaine. In few cases, this rare focal arrhythmia may be also suppressed by adenosine and/or verapamil, which suggests a diversity of electrophysiologic substrates that deserve to be accurately identified.
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http://dx.doi.org/10.1111/anec.12014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932048PMC
January 2013

High-degree right bundle branch block obscuring the diagnosis of Brugada electrocardiographic pattern.

Heart Rhythm 2012 Jun 1;9(6):974-6. Epub 2012 Feb 1.

Division of Cardiology, Centro de Arritmias Cardíacas of Buenos Aires City, Ramos Mejía Hospital, Facultad de Ciencias Medicas, Pontificia Universidad Católica Argentina.

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http://dx.doi.org/10.1016/j.hrthm.2012.01.028DOI Listing
June 2012

Distinct pharmacologic substrate in lidocaine-sensitive, repetitive atrial tachycardia.

J Cardiovasc Pharmacol Ther 2012 Jun 31;17(2):146-52. Epub 2011 Aug 31.

Centro de Arritmias Cardíacas, Goverment of Buenos Aires City, Buenos Aires, Argentina.

Lidocaine-sensitive, repetitive atrial tachycardia is an uncommon arrhythmia. The electrophysiologic substrate is still unknown, and the pharmacologic responses have not been fully explored. The aim of this study was to investigate the effects of intravenous adenosine and verapamil in patients with lidocaine-sensitive atrial tachycardia. In 9 patients with repetitive uniform atrial tachycardia, the response to intravenous adenosine (12 mg), lidocaine (1 mg/kg body weight), and verapamil (10 mg) were sequentially investigated. Simultaneous 12-lead electrocardiogram (ECG) was recorded at baseline and continuously monitored thereafter. Tracings were obtained at regularly timed intervals right after the administration of each drug to evaluate changes in the arrhythmia characteristics. Repetitive atrial tachycardia was abolished by intravenous lidocaine in the 9 patients within the first 2 minutes after the end of injection. Adenosine suppressed the arrhythmia in 2 patients and shortened the runs of atrial ectopic activity in 1 patient, while verapamil was effective in 2 patients, 1 of them insensitive to adenosine and the other 1 sensitive to this agent. In 5 patients, the arrhythmia was abolished by radiofrequency ablation at different sites of the right atrium. Lidocaine-sensitive atrial tachycardia may eventually be also suppressed by adenosine and/or verapamil. This suggests that this enigmatic arrhythmia may be caused by different underlying electrophysiologic substrates and that at least in some cases, delayed afterdepolarizations seem to play a determining role.
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http://dx.doi.org/10.1177/1074248411418971DOI Listing
June 2012

In silico study of the inhibition of DNA polymerase by a novel catalpol derivative.

J Mol Model 2011 Oct 13;17(10):2717-23. Epub 2011 Jan 13.

IMASL-CONICET, Universidad Nacional de San Luis. Ejército, de los Andes 950, 5700 San Luis, Argentina.

In this work, a novel catalpol derivative (6,10,2',6'-tetraacetyl-O-catalpol), which was previously obtained by our group and shown experimentally to inhibit a type of Taq DNA polymerase, was studied in silico. Studies of the interaction of 6,10,2',6'-tetraacetyl-O-catalpol with the Klentaq fragment of the Taq DNA polymerase I from Thermus aquaticus helped to elucidate the mechanism of inhibition of the enzyme, and offered valuable information that can be used to propose substrate structural modifications aimed at increasing the binding affinity. Classical and semi-empirical methods were used to characterize the conformational preferences of this organic compound in solution. Using docking simulations, the most probable binding mode was found, and the stabilities of the docked solutions were tested in a series of molecular dynamics experiments. Results indicated that the mechanism of inhibition may be competitive, which agrees with previous binding experiments done with 6,10,2',6'-tetraacetyl-O-catalpol.
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http://dx.doi.org/10.1007/s00894-010-0938-7DOI Listing
October 2011

Reversal of primary and pseudo-primary T wave abnormalities by ventricular pacing. A novel manifestation of cardiac memory.

J Interv Card Electrophysiol 2010 Jun 24;28(1):23-33. Epub 2010 Mar 24.

Centro de Arritmias Cardíacas de la Ciudad Autónoma de Buenos Aires, Division of Cardiology, Ramos Mejía Hospital, Buenos Aires, Argentina.

Aims: "Cardiac memory" refers to abnormal T waves (TW) appearing after transient periods of altered ventricular depolarization. The aim of the study was to test the hypothesis that in the presence of abnormal TW, short periods of tailored ventricular pacing (VP) can be followed by normalization of ventricular repolarization.

Methods: Ten patients with normal TW (control group) and 18 patients with abnormal TW (study group) underwent 15 min of VP at a cycle length of 500 ms. In the control group, VP was performed from the right ventricular apex, and in the study group from right or left ventricular sites that resulted in paced QRS complexes of opposite polarity to that of the abnormal TW. Before and after VP, atrial pacing was maintained at a stable cycle length. Simultaneous 12-lead electrocardiography (ECG) was recorded before, during, and following VP to assess changes in TW polarity, amplitude, electrical axis, QTc interval, and QTc interval dispersion.

Results: As expected, VP was followed by memory-induced changes in TW in eight of ten patients in the control group. Mean T wave axis shifted from +60 degrees + or - 21.2 degrees to +23.5 degrees + or - 50.7 degrees (p = 0.01) in the frontal plane. In the study group, complete or partial normalization of TW occurred in 17 of 18 patients. Mean T wave axis shifted from -23.7 degrees + or - 22.9 degrees to +19.7 degrees + or - 34.7 degrees (p < 0.0002) in the frontal plane when paced from right ventricular outflow tract. The QTc interval shortened after VP both in the control group (424 + or - 25 vs. 399 + or - 27 ms; p = 0.007) and in the study group (446 + or - 26 vs. 421 + or - 22 ms; p < 0.0002). No significant changes were found in QTc interval dispersion.

Conclusions: Transient changes in the sequence of ventricular activation may either induce or normalize abnormal TW. The background of preceding ventricular depolarization needs to be taken into account before determining the clinical significance of a given pattern of ventricular repolarization.
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http://dx.doi.org/10.1007/s10840-010-9473-9DOI Listing
June 2010

Supernormal conduction in the anomalous bundles of the Wolff-Parkinson-White syndrome: an overlooked electrophysiologic property with potential clinical implications.

J Cardiovasc Pharmacol Ther 2007 Sep;12(3):181-91

Cátedra de Cardiología, Facultad de Medicina, Pontificia Universidad Católica Argentina.

The anterograde refractory period (RP) of the accessory pathway (AP) is the main determinant factor of ventricular rate during atrial fibrillation in the Wolff-Parkinson-White (WPW) syndrome. We describe 3 examples of anterograde supernormal conduction (SNC) and 1 of retrograde SNC in APs. The paradoxical early recovery of propagation due to SNC, well inside a prolonged anterograde RP in the AP, may play a relevant role to determine the rate of ventricular response during atrial fibrillation, eventually leading to extremely fast ventricular rates, syncope, and even ventricular fibrillation in patients with WPW syndrome supposed a priori to be exposed to a low risk of sudden cardiac death. This may require very precise conditions, including an enhanced adrenergic influence on the heart. Retrograde SNC in APs may also participate in the mechanism of paroxysmal supraventricular tachycardias that are not easily induced by programmed cardiac stimulation.
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http://dx.doi.org/10.1177/1074248407304183DOI Listing
September 2007

Inappropriate sinus tachycardia may be related to an immunologic disorder involving cardiac beta andrenergic receptors.

Heart Rhythm 2006 Oct 15;3(10):1182-6. Epub 2006 Jun 15.

Division of Cardiology, Ramos Mejía Hospital, Buenos Aires, Argentina.

Background: The mechanisms underlying inappropriate sinus tachycardia are not fully known. An autonomic imbalance seems to play a role, but no attempts have been made to investigate a relationship between this arrhythmia and the antiautonomic membrane receptor antibodies found in other heart disorders and arrhythmias.

Objective: The purpose of this study was to investigate the prevalence and the functional and biochemical effects of circulating antiautonomic receptor antibodies in patients with inappropriate sinus tachycardia.

Methods: We studied 21 patients with inappropriate sinus tachycardia and 15 healthy volunteers. The chronotropic effects of the IgG fractions (also of affinity-purified anti-beta1 adrenergic receptor antibodies in selected cases) were assessed on cultured cardiomyocytes before and after exposure to atropine and propranolol. The effects of the IgG fractions from five patients and five healthy volunteers on cAMP production were evaluated in COS-7 cells transfected with genes encoding for beta1 or beta2 adrenergic receptor.

Results: The IgG fractions from patients with inappropriate sinus tachycardia exerted a positive chronotropic action with a high prevalence of anti-beta receptor antibodies (52%) and induced a clear-cut and long lasting increment of cAMP. No anti-M2 cholinergic receptor antibodies were found. The IgG fractions from healthy volunteers did not contain antiautonomic receptor antibodies.

Conclusions: Our results suggest, for the first time, a link between inappropriate sinus tachycardia and circulating anti-beta adrenergic receptor antibodies that induce a persistent increment in cAMP production. This finding offers new insight into the physiopathology of inappropriate sinus tachycardia with potential therapeutic consequences.
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http://dx.doi.org/10.1016/j.hrthm.2006.06.011DOI Listing
October 2006

Recording of high V1-V3 precordial leads may be essential to the diagnosis of Brugada syndrome during the ajmaline test.

J Cardiovasc Pharmacol Ther 2006 Jun;11(2):153-5

Division of Cardiology, Hospital General de Agudos Jose M. Ramos Mejia, General Urquiza 609, C1221ADC Buenos Aires, Argentina.

Sodium channel-blocking agents are routinely used to unveil the Brugada syndrome in patients in whom the typical electrocardiographic pattern is absent or doubtful. In this article, the authors report a patient with syncopal episodes of unknown origin in whom the conventional electrocardiographic result was normal and a negligibly small "saddle back" type repolarization was present in lead V2 recorded 2 intercostal spaces above the conventional site. Intravenous ajmaline (50 mg) did not elicit the type 1 pattern of the Brugada syndrome in the precordial leads obtained at their usual level, but a clear-cut coved-type repolarization was apparent in high right precordial leads. These findings indicate that high precordial leads should be routinely recorded while assessing the ajmaline test in patients suspected of having the Brugada syndrome.
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http://dx.doi.org/10.1177/1074248406288760DOI Listing
June 2006