Massimiliano Zaniboni | Università degli Studi di Parma (Italy) (original) (raw)
Papers by Massimiliano Zaniboni
Biophysical Journal, 2017
Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer about this process is available in the located, click Request Permissions in the middle column of the Web page under Services. Further information Editorial Office. Once the online version of the published article for which permission is being requested is can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculation Researchin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on February 26,
Biophysical Journal, 2002
The role of water in iiitluciiig tlie bioelectret. state of lysozyme has been previously stated. ... more The role of water in iiitluciiig tlie bioelectret. state of lysozyme has been previously stated. 111 order to attribute each peak of t.lie coiiiplex TSDC! lysozyine spect.runi to water iiitlucetl polarization process occurring at a given polypeptide cliaiii segment, we have measured and compared the TSDC and infrared absorption spect,ra of several aiiiitioacitlic synthetic Iioniopolytiiers at different Iiytlratioii levels. The A-band (135-160 I<), present. in all t lie lioiiiopolyiiiers investigated, is due to water iiiolecule reorieiitatioii around tlie pept.itle bond. Tlie B-band (- 215 E;) is related to the relaxat.ion of the side chains, whose niobility and reorientation paranieters are affect,etl by the hydration level.
Experimental physiology, 2006
We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis i... more We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of alpha-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic press...
In normal rats, we analysed the arrhythmogenic role of intrinsic action potential duration (APD) ... more In normal rats, we analysed the arrhythmogenic role of intrinsic action potential duration (APD) heterogeneity. In each animal, ventricular arrhythmic events (VAEs) occurring spontaneously and during the exposure to an acute social challenge were telemetrically recorded. Action potentials were recorded from isolated left ventricular myocytes, at a pacing rate of 5 Hz (patch clamp: current-clamp mode). APDs were measured at -20 mV, -30 mV, -40 mV, -50 mV and -60 mV. The difference between the shortest and the longest APD was also computed, as an index of individual APD heterogeneity. Animals predisposed to stress-induced arrhythmias showed higher values of APD and APD heterogeneity as compared with the remaining rats. We concluded that, in the normal heart, a large intrinsic APD heterogeneity resulting from specific electrophysiological properties of ventricular myocytes is not in itself arrhythmogenic, but can predispose towards arrhythmia development under certain conditions, such ...
Vascular Pharmacology, 2015
Biophysical Journal, Feb 1, 2018
Nutrients, Jan 16, 2016
Background: Little information is currently available concerning the relative contribution of car... more Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues. Results: In vitro data indicated that, besides cardiomyocytes, neonatal fibroblasts contribute to generating initial changes in the myocardial environment, in terms of pro-inflammatory cytokine expression. These findings were mostly confirmed at the myocardial tissue level in diabetic rats, after three weeks of hyperglycemia. Specifically, monocyte chemoattractant protein-1 and Fractalkine...
Exp Physiol, 2007
Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously cha... more Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously characterized in isolated cardiomyocytes for sudden changes in constant CL and for pre-/postmature stimuli following constant pacing trains. However, random fluctuations characterize both physiological sinus rhythm (up to 10% of mean CL) and intrinsic beat-to-beat APD at constant pacing rate. We analysed the beat-to-beat sensitivity of each APD to the preceding CL during constant-sudden, random or linearly changing pacing trains in single patch clamped rat left ventricular myocytes, in the absence of the autonomic and electrotonic effects that modulate rate dependency in the intact heart. Beat-to-beat variability of APD at -60 mV (APD(-60 mV)), quantified as S.D. over 10-beat sequences, increased with corresponding mean APD. When measured as coefficient of variability (CV), APD(-60 mV) variability was inversely proportional to pacing frequency (from 1.2% at 5 Hz to 3.2% at 0.2 Hz). It was increased, at a basic CL (BCL) of 250 ms, by 55% by the L-type calcium current (I(CaL)) blocker nifedipine, and decreased by 23% by the transient-outward potassium current (I(to)) blocker 4-aminopyridine. Variability of APD at BCL of 250 ms prevented the detection of random changes of CL smaller than approximately 5%. Ten per cent random changes in CL were detected as a 40% increase in CV of APD and tended to correlate with it (r = 0.43). Block of I(CaL) depressed this correlation (r = 0.23), whereas block of I(to) significantly increased it (r = 0.67); this was similar with linearly changing CL ramps (ranging +/-10% and +/-20% of 250 ms). We conclude that beat-to-beat APD variability, a major determinant of the propensity for development of arrhythmia in the heart, is present in isolated myocytes, where it is dependent on mean APD and pacing rate. Action potential duration shows a beat-to-beat positive correlation with preceding randomly/linearly changing CL, which can be pharmacologically modulated.
[1991 Proceedings] 7th International Symposium on Electrets (ISE 7), 1991
ABSTRACT In order to attribute each peak of the complex TSDC (thermally stimulated depolarization... more ABSTRACT In order to attribute each peak of the complex TSDC (thermally stimulated depolarization current) lysozyme spectrum to a water-induced polarization process occurring at a given polypeptide chain segment, the authors have measured and compared the TSDC and infrared absorption spectra of several aminoacidic synthetic homopolymers at different hydration levels. The A-band (135-160 K), present in all the homopolymers investigated, is due to water molecule reorientation around the peptide bond. The B-band (~215 K) is related to the relaxation of the side chains, whose mobility and reorientation parameters are affected by the hydration level
Creative Education, 2012
A scientific controversy retains often some controversial sides after its fundamentals has well b... more A scientific controversy retains often some controversial sides after its fundamentals has well been explained. This is particularly true for the controversy that arose in Italy in the second half of the eighteen century between the anatomist Luigi Galvani, and the physicist Alessandro Volta, around the intrinsic nature of nerve and muscular function. The two scientists were providing, almost simultaneously from the University of Bologna and Pavia respectively, two quite different explanations for the property of muscles of being electrically excitable and contract as a consequence. Science seemed then to touch the very intrinsic mechanism of living processes. Despite the fact that one of the two explanations was explaining better than the other, the weaker mechanism won the battle at the time. The biophysical mechanism of nerve excitability has then been clarified in 1950 by Hodgkin and Huxley, who later won the Nobel prize for their work. They unequivocally showed that Galvani was right and Volta quite wrong. Only specialists though notice that the Galvani-Volta controversy is frequently still thought wrong in schools. In this brief essay I want to show how easy-to-handle computer models can unveil where the subtle source of the controversy was hidden, and how an interdisciplinary approach can help drawing light into the multiple aspects of this extraordinary story.
American Journal of Physiology Heart and Circulatory Physiology, Aug 1, 1997
Electrotonic effects of electrically coupling atrioventricular (AV) nodal cells to each other and... more Electrotonic effects of electrically coupling atrioventricular (AV) nodal cells to each other and to real and passive models of atrial and ventricular cells were studied using a technique that does not require functional gap junctions. Membrane potential was measured in each cell using suction pipettes. Mutual entrainment of two spontaneously firing AV nodal cells was achieved with a junctional resistance (Rj) of 500 M omega, which corresponds to only 39 junctional channels, assuming a single-channel conductance of 50 pS. Coupling of AV nodal and atrial cells at Rj of 50 M omega caused hyperpolarization of the nodal cell, decreasing its action potential duration and either slowing or blocking diastolic depolarization in the AV node myocyte. Opposite changes occurred in the atrial action potential. When AV nodal and ventricular cells were coupled at Rj of 50 M omega, nodal diastolic potential was markedly hyperpolarized and diastolic depolarization was completely blocked with little change in ventricular diastolic potential. However, coupling did elicit marked changes in the action potential duration of both cells, with prolongation in the nodal cell and shortening in the ventricular cell. Nodal maximum upstroke velocity was increased by both atrial and ventricular coupling, as expected from the hyperpolarization that occurred. With an Rj of 50 M omega, spontaneous firing was blocked in all single AV nodal pacemaker cells during coupling to a real or passive model of an atrial or ventricular cell. These results demonstrate that action potential formation and waveform in a single AV nodal cell is significantly affected by electrical coupling to other myocytes.
BioMed Research International, 2015
Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically... more Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation G Kr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in I CaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies.
Acta bio-medica de L'Ateneo parmense : organo della Società di medicina e scienze naturali di Parma, 2001
Spread and modulation of electrical activity in cardiac tissue requires intercellular transfer of... more Spread and modulation of electrical activity in cardiac tissue requires intercellular transfer of current via gap junctions, specialised regions of densely packed ionic channels. Electrotonic interaction is determined not merely by intercellular electrical resistance (Rj) but rather by the interplay of Rj and sarcolemmal passive and active electrical properties (Zaniboni et al., Spitzer et al.). In this work we combined a well established protocol to measure Rj in cell pairs (Weingart e Maurer) with a stimulation protocol which allowed to simultaneously study parameters relative to action potential transfer during sequential stimulation. Current clamp experiments, performed on cardiomyocyte pairs held in double-patch configuration, allowed to simultaneously monitor, at a relatively high frequency (1 Hz), membrane resistance (Rm), resting potential (Vm), maximum depolarization rate (dv/dtmax) and time to peak of dv/dtmax in both cells as well as Rj. Spontaneous electrical uncoupling ...
American journal of physiology. Heart and circulatory physiology, 2001
In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated r... more In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated rats (SO) chronically instrumented for telemetry electrocardiogram recording, we investigated the mechanisms of arrhythmogenesis in moderate cardiac hypertrophy, with an approach from "in vivo" toward the cellular level, analyzing 1) stress-induced cardiac arrhythmias in all rats and 2) myocardial fibrosis in 35 animals and action potential duration and density of hyperpolarization-activated current in 19 others at the ventricular level. Aortic banding increased arterial blood pressure, cardiac weight, and ventricular myocyte volume by 11, 25, and 14%, respectively (P < 0.001-0.05). Ventricular arrhythmias occurred at similar rates in AC and SO rats throughout the stress procedure. Action potential duration and hyperpolarization-activated current were about twice as great and myocardial fibrosis about four times greater in AC animals (P < 0.005-0.05). Electrocardiogram dat...
Europace, 2014
To adopt a novel three-dimensional (3D) representation of cardiac action potential (AP) to compac... more To adopt a novel three-dimensional (3D) representation of cardiac action potential (AP) to compactly visualize dynamical properties of human cellular ventricular repolarization. We have recently established a novel 3D representation of cardiac AP, which is based on the iterative measurement of instantaneous ion current-voltage profiles during the course of an AP. Such an approach has been originally developed on real patch-clamped ventricular cells, and subsequently improved in silico on several cardiac ventricular AP models of different mammals, and on models of different AP types of the human heart. We apply it here on two different models of human ventricular AP, and show that it compactly provides further insights into repolarization dynamics. The 3D representation of the AP includes equilibrium points during repolarization, and can be screened in terms of what we have shown to be a region, during late repolarization, when membrane conductance becomes negative and repolarization therefore auto-regenerative. We have called this time window auto-regenerative-repolarization-phase (ARRP). In addition to previous findings obtained through the same procedure, we show here that 3D current-voltage-time representations of human ventricular AP allow compact visualization of dynamical properties, which are relevant for the physiology and pathology of ventricular repolarization. In particular, we suggest that the volume under the current surface corresponding to the ARRP might be used as a predictor of safety of repolarization, in single cells and during AP conduction in cell pairs.
Biophysical Journal, 2017
Information about reprints can be found online at: Reprints: document. Permissions and Rights Que... more Information about reprints can be found online at: Reprints: document. Permissions and Rights Question and Answer about this process is available in the located, click Request Permissions in the middle column of the Web page under Services. Further information Editorial Office. Once the online version of the published article for which permission is being requested is can be obtained via RightsLink, a service of the Copyright Clearance Center, not theCirculation Researchin Requests for permissions to reproduce figures, tables, or portions of articles originally publishedPermissions: by guest on February 26,
Biophysical Journal, 2002
The role of water in iiitluciiig tlie bioelectret. state of lysozyme has been previously stated. ... more The role of water in iiitluciiig tlie bioelectret. state of lysozyme has been previously stated. 111 order to attribute each peak of t.lie coiiiplex TSDC! lysozyine spect.runi to water iiitlucetl polarization process occurring at a given polypeptide cliaiii segment, we have measured and compared the TSDC and infrared absorption spect,ra of several aiiiitioacitlic synthetic Iioniopolytiiers at different Iiytlratioii levels. The A-band (135-160 I<), present. in all t lie lioiiiopolyiiiers investigated, is due to water iiiolecule reorieiitatioii around tlie pept.itle bond. Tlie B-band (- 215 E;) is related to the relaxat.ion of the side chains, whose niobility and reorientation paranieters are affect,etl by the hydration level.
Experimental physiology, 2006
We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis i... more We have analysed alterations of alpha-skeletal actin expression and volume fraction of fibrosis in the ventricular myocardium and their functional counterpart in terms of arrhythmogenesis and haemodynamic variables, in rats with different degrees of compensated cardiac hypertrophy induced by infra-renal abdominal aortic coarctation. The following coarctation calibres were used: 1.3 (AC1.3 group), 0.7 (AC0.7) and 0.4 mm (AC0.4); age-matched rats were used as controls (C group). One month after surgery, spontaneous and sympathetic-induced ventricular arrhythmias were telemetrically recorded from conscious freely moving animals, and invasive haemodynamic measurements were performed in anaesthetized animals. After killing, subgroups of AC and C rats were used to evaluate in the left ventricle the expression and spatial distribution of alpha-skeletal actin and the amount of perivascular and interstitial fibrosis. As compared with C, all AC groups exhibited higher values of systolic press...
In normal rats, we analysed the arrhythmogenic role of intrinsic action potential duration (APD) ... more In normal rats, we analysed the arrhythmogenic role of intrinsic action potential duration (APD) heterogeneity. In each animal, ventricular arrhythmic events (VAEs) occurring spontaneously and during the exposure to an acute social challenge were telemetrically recorded. Action potentials were recorded from isolated left ventricular myocytes, at a pacing rate of 5 Hz (patch clamp: current-clamp mode). APDs were measured at -20 mV, -30 mV, -40 mV, -50 mV and -60 mV. The difference between the shortest and the longest APD was also computed, as an index of individual APD heterogeneity. Animals predisposed to stress-induced arrhythmias showed higher values of APD and APD heterogeneity as compared with the remaining rats. We concluded that, in the normal heart, a large intrinsic APD heterogeneity resulting from specific electrophysiological properties of ventricular myocytes is not in itself arrhythmogenic, but can predispose towards arrhythmia development under certain conditions, such ...
Vascular Pharmacology, 2015
Biophysical Journal, Feb 1, 2018
Nutrients, Jan 16, 2016
Background: Little information is currently available concerning the relative contribution of car... more Background: Little information is currently available concerning the relative contribution of cardiac parenchymal and stromal cells in the activation of the pro-inflammatory signal cascade, at the initial stages of diabetes. Similarly, the effects of early resveratrol (RSV) treatment on the negative impact of diabetes on the different myocardial cell compartments remain to be defined. Methods: In vitro challenge of neonatal cardiomyocytes and fibroblasts to high glucose and in vivo/ex vivo experiments on a rat model of Streptozotocin-induced diabetes were used to specifically address these issues. Results: In vitro data indicated that, besides cardiomyocytes, neonatal fibroblasts contribute to generating initial changes in the myocardial environment, in terms of pro-inflammatory cytokine expression. These findings were mostly confirmed at the myocardial tissue level in diabetic rats, after three weeks of hyperglycemia. Specifically, monocyte chemoattractant protein-1 and Fractalkine...
Exp Physiol, 2007
Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously cha... more Adaptation of action potential duration (APD) to pacing cycle length (CL) has been previously characterized in isolated cardiomyocytes for sudden changes in constant CL and for pre-/postmature stimuli following constant pacing trains. However, random fluctuations characterize both physiological sinus rhythm (up to 10% of mean CL) and intrinsic beat-to-beat APD at constant pacing rate. We analysed the beat-to-beat sensitivity of each APD to the preceding CL during constant-sudden, random or linearly changing pacing trains in single patch clamped rat left ventricular myocytes, in the absence of the autonomic and electrotonic effects that modulate rate dependency in the intact heart. Beat-to-beat variability of APD at -60 mV (APD(-60 mV)), quantified as S.D. over 10-beat sequences, increased with corresponding mean APD. When measured as coefficient of variability (CV), APD(-60 mV) variability was inversely proportional to pacing frequency (from 1.2% at 5 Hz to 3.2% at 0.2 Hz). It was increased, at a basic CL (BCL) of 250 ms, by 55% by the L-type calcium current (I(CaL)) blocker nifedipine, and decreased by 23% by the transient-outward potassium current (I(to)) blocker 4-aminopyridine. Variability of APD at BCL of 250 ms prevented the detection of random changes of CL smaller than approximately 5%. Ten per cent random changes in CL were detected as a 40% increase in CV of APD and tended to correlate with it (r = 0.43). Block of I(CaL) depressed this correlation (r = 0.23), whereas block of I(to) significantly increased it (r = 0.67); this was similar with linearly changing CL ramps (ranging +/-10% and +/-20% of 250 ms). We conclude that beat-to-beat APD variability, a major determinant of the propensity for development of arrhythmia in the heart, is present in isolated myocytes, where it is dependent on mean APD and pacing rate. Action potential duration shows a beat-to-beat positive correlation with preceding randomly/linearly changing CL, which can be pharmacologically modulated.
[1991 Proceedings] 7th International Symposium on Electrets (ISE 7), 1991
ABSTRACT In order to attribute each peak of the complex TSDC (thermally stimulated depolarization... more ABSTRACT In order to attribute each peak of the complex TSDC (thermally stimulated depolarization current) lysozyme spectrum to a water-induced polarization process occurring at a given polypeptide chain segment, the authors have measured and compared the TSDC and infrared absorption spectra of several aminoacidic synthetic homopolymers at different hydration levels. The A-band (135-160 K), present in all the homopolymers investigated, is due to water molecule reorientation around the peptide bond. The B-band (~215 K) is related to the relaxation of the side chains, whose mobility and reorientation parameters are affected by the hydration level
Creative Education, 2012
A scientific controversy retains often some controversial sides after its fundamentals has well b... more A scientific controversy retains often some controversial sides after its fundamentals has well been explained. This is particularly true for the controversy that arose in Italy in the second half of the eighteen century between the anatomist Luigi Galvani, and the physicist Alessandro Volta, around the intrinsic nature of nerve and muscular function. The two scientists were providing, almost simultaneously from the University of Bologna and Pavia respectively, two quite different explanations for the property of muscles of being electrically excitable and contract as a consequence. Science seemed then to touch the very intrinsic mechanism of living processes. Despite the fact that one of the two explanations was explaining better than the other, the weaker mechanism won the battle at the time. The biophysical mechanism of nerve excitability has then been clarified in 1950 by Hodgkin and Huxley, who later won the Nobel prize for their work. They unequivocally showed that Galvani was right and Volta quite wrong. Only specialists though notice that the Galvani-Volta controversy is frequently still thought wrong in schools. In this brief essay I want to show how easy-to-handle computer models can unveil where the subtle source of the controversy was hidden, and how an interdisciplinary approach can help drawing light into the multiple aspects of this extraordinary story.
American Journal of Physiology Heart and Circulatory Physiology, Aug 1, 1997
Electrotonic effects of electrically coupling atrioventricular (AV) nodal cells to each other and... more Electrotonic effects of electrically coupling atrioventricular (AV) nodal cells to each other and to real and passive models of atrial and ventricular cells were studied using a technique that does not require functional gap junctions. Membrane potential was measured in each cell using suction pipettes. Mutual entrainment of two spontaneously firing AV nodal cells was achieved with a junctional resistance (Rj) of 500 M omega, which corresponds to only 39 junctional channels, assuming a single-channel conductance of 50 pS. Coupling of AV nodal and atrial cells at Rj of 50 M omega caused hyperpolarization of the nodal cell, decreasing its action potential duration and either slowing or blocking diastolic depolarization in the AV node myocyte. Opposite changes occurred in the atrial action potential. When AV nodal and ventricular cells were coupled at Rj of 50 M omega, nodal diastolic potential was markedly hyperpolarized and diastolic depolarization was completely blocked with little change in ventricular diastolic potential. However, coupling did elicit marked changes in the action potential duration of both cells, with prolongation in the nodal cell and shortening in the ventricular cell. Nodal maximum upstroke velocity was increased by both atrial and ventricular coupling, as expected from the hyperpolarization that occurred. With an Rj of 50 M omega, spontaneous firing was blocked in all single AV nodal pacemaker cells during coupling to a real or passive model of an atrial or ventricular cell. These results demonstrate that action potential formation and waveform in a single AV nodal cell is significantly affected by electrical coupling to other myocytes.
BioMed Research International, 2015
Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically... more Initiation and maintenance of atrial fibrillation (AF) is often associated with pharmacologically or pathologically induced bradycardic states. Even drugs specifically developed in order to counteract cardiac arrhythmias often combine their action with bradycardia and, in turn, with development of AF, via still largely unknown mechanisms. This study aims to simulate action potential (AP) conduction between sinoatrial node (SAN) and atrial cells, either arranged in cell pairs or in a one-dimensional strand, where the relative amount of SAN membrane is made varying, in turn, with junctional resistance. The source-sink relationship between the two membrane types is studied in control conditions and under different simulated chronotropic interventions, in order to define a safety factor for pacemaker-to-atrial AP conduction (SASF) for each treatment. Whereas antiarrhythmic-like interventions which involve downregulation of calcium channels or of calcium handling decrease SASF, the simulation of Ivabradine administration does so to a lesser extent. Particularly interesting is the increase of SASF observed when downregulation G Kr, which simulates the administration of class III antiarrhythmic agents and is likely sustained by an increase in I CaL. Also, the increase in SASF is accompanied by a decreased conduction delay and a better entrainment of repolarization, which is significant to anti-AF strategies.
Acta bio-medica de L'Ateneo parmense : organo della Società di medicina e scienze naturali di Parma, 2001
Spread and modulation of electrical activity in cardiac tissue requires intercellular transfer of... more Spread and modulation of electrical activity in cardiac tissue requires intercellular transfer of current via gap junctions, specialised regions of densely packed ionic channels. Electrotonic interaction is determined not merely by intercellular electrical resistance (Rj) but rather by the interplay of Rj and sarcolemmal passive and active electrical properties (Zaniboni et al., Spitzer et al.). In this work we combined a well established protocol to measure Rj in cell pairs (Weingart e Maurer) with a stimulation protocol which allowed to simultaneously study parameters relative to action potential transfer during sequential stimulation. Current clamp experiments, performed on cardiomyocyte pairs held in double-patch configuration, allowed to simultaneously monitor, at a relatively high frequency (1 Hz), membrane resistance (Rm), resting potential (Vm), maximum depolarization rate (dv/dtmax) and time to peak of dv/dtmax in both cells as well as Rj. Spontaneous electrical uncoupling ...
American journal of physiology. Heart and circulatory physiology, 2001
In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated r... more In 47 male adult Wistar rats with 4-wk aortic coarctation (AC) and 39 age-matched sham-operated rats (SO) chronically instrumented for telemetry electrocardiogram recording, we investigated the mechanisms of arrhythmogenesis in moderate cardiac hypertrophy, with an approach from "in vivo" toward the cellular level, analyzing 1) stress-induced cardiac arrhythmias in all rats and 2) myocardial fibrosis in 35 animals and action potential duration and density of hyperpolarization-activated current in 19 others at the ventricular level. Aortic banding increased arterial blood pressure, cardiac weight, and ventricular myocyte volume by 11, 25, and 14%, respectively (P < 0.001-0.05). Ventricular arrhythmias occurred at similar rates in AC and SO rats throughout the stress procedure. Action potential duration and hyperpolarization-activated current were about twice as great and myocardial fibrosis about four times greater in AC animals (P < 0.005-0.05). Electrocardiogram dat...
Europace, 2014
To adopt a novel three-dimensional (3D) representation of cardiac action potential (AP) to compac... more To adopt a novel three-dimensional (3D) representation of cardiac action potential (AP) to compactly visualize dynamical properties of human cellular ventricular repolarization. We have recently established a novel 3D representation of cardiac AP, which is based on the iterative measurement of instantaneous ion current-voltage profiles during the course of an AP. Such an approach has been originally developed on real patch-clamped ventricular cells, and subsequently improved in silico on several cardiac ventricular AP models of different mammals, and on models of different AP types of the human heart. We apply it here on two different models of human ventricular AP, and show that it compactly provides further insights into repolarization dynamics. The 3D representation of the AP includes equilibrium points during repolarization, and can be screened in terms of what we have shown to be a region, during late repolarization, when membrane conductance becomes negative and repolarization therefore auto-regenerative. We have called this time window auto-regenerative-repolarization-phase (ARRP). In addition to previous findings obtained through the same procedure, we show here that 3D current-voltage-time representations of human ventricular AP allow compact visualization of dynamical properties, which are relevant for the physiology and pathology of ventricular repolarization. In particular, we suggest that the volume under the current surface corresponding to the ARRP might be used as a predictor of safety of repolarization, in single cells and during AP conduction in cell pairs.