Isaac Aidonidis - Academia.edu (original) (raw)
Papers by Isaac Aidonidis
Your article is protected by copyright and all rights are held exclusively by Springer Science+Bu... more Your article is protected by copyright and all rights are held exclusively by Springer Science+Business Media, LLC, part of Springer Nature. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to selfarchive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation ... more Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation in intact animals; however, its efficacy in the setting of atrial tachycardia (AT) is unknown. The purpose of this study was to investigate the effects of RAN alone or in combination with amiodarone (AMIO) on rapid pacing-evoked right AT in rabbit hearts. Right atrial monophasic action potentials (MAPs) were recorded in 11 anesthetized rabbits, using combination MAP pacing catheters. Vulnerability to AT was tested by employing consecutive trains of rapid burst pacing prior to and after 2.4 mg/kg of RAN alone delivered intravenously and then in combination with 3 mg/kg of AMIO as a 15-minute infusion. Primary endpoints were postdrug AT reproducibility as well as cycle length (CL) and tachycardia duration. MAP duration at 75% repolarization and the effective refractory period (ERP) were assessed during programmed pacing to calculate the atrial postrepolarization refractoriness (aPRR = ERP-MAPD 75%). AT was elicited in eight out of 11 rabbits; only these animals were included for further investigation. RAN did not abolish the inducibility of AT in any experiment; however, it prolonged its CL (baseline vs. RAN: 120 ± 16 ms vs. 138 ± 18 ms; p = 0.053). Supplemental AMIO further increased the AT CL (baseline vs. RAN + AMIO: 120 ± 16 ms vs. 152 ± 23 ms; p = 0.006), without affecting arrhythmia reinducibility. Slowing of the tachycardia after RAN or RAN + AMIO was associated with spontaneous termination of the arrhythmia. RAN prolonged the aPRR significantly, while AMIO in addition to RAN potentiated this effect. Neither RAN alone nor its combination with AMIO abolished the elicitation of AT in this model. However, both agents synergistically prolonged the aPRR, resulting in the slowing of AT and promoting spontaneous termination of the arrhythmia.
The involvement of the autonomic nervous system in the pathogenesis of ventricular arrhythmias ha... more The involvement of the autonomic nervous system in the pathogenesis of ventricular arrhythmias has stimulated interest in studying alterations of the cardiac innervation in experimental models of myocardial infarction. Enhanced sympathetic activation can occasionally trigger ventricular tachycardias in subjects having normal hearts [17, 27]; however, such arrhythmias are frequently provoked under myocardial ischaemia [32]. The arrhythmogenic potential of sympathetic hyperactivity was shown to be mediated by left-sided nerves or ganglia; their stimulation during acute myocardial ischaemia led to malignant arrhythmias including ventricular fibrillation [26, 29, 30].
PubMed, Feb 28, 2014
The impact of ranolazine, an anti-ishemic agent with antiarrhythmic properties, on paroxysmal atr... more The impact of ranolazine, an anti-ishemic agent with antiarrhythmic properties, on paroxysmal atrial fibrillation (PAF) in patients with coronary artery disease (CAD) remains unclear. Pacing devices can be useful tools for disclosing even asymptomatic PAF. Purpose of this study is to assess the effect of ranolazine on atrial fibrillation (AF), in patients with CAD, PAF and a dual-chamber pacemaker. We studied 74 patients with CAD, PAF, and sick sinus syndrome or atrio-ventricular block, treated with pacemakers capable to detect PAF episodes. The total time in AF, AF burden, and the number of PAF episodes within the last 6 months before enrolment in the study, mean AF duration per episode, and the QTc interval were initially assessed. Subsequently, patients were randomized into additional treatment with ranolazine (375 mg twice daily) or placebo. Following six months of treatment, all parameters were reassessed and compared to those before treatment. Ranolazine was associated with shorter total AF duration (81.56±45.24 hours versus 68.71±34.84 hours, p=0.002), decreased AF burden (1.89±1.05% versus 1.59±0.81%, p=0.002), and shortened mean AF duration (1.15±0.41 hours versus 0.92±0.35 hours, p=0.01). In the placebo group no such differences were observed. In both groups, no significant differences in the number of PAF episodes and QTc duration were observed. We conclude that in patients with CAD and PAF, ranolazine reduces the total time in AF, AF burden, and mean AF duration. These findings may imply additional antiarrhythmic properties of ranolazine on atrial myocardium and might indicate the necessity of its use in ischemic patients with PAF.
Journal of surgery and research, 2020
Objectives: Aortic valve replacement (AVR) is often associated with intraoperative ventricular fi... more Objectives: Aortic valve replacement (AVR) is often associated with intraoperative ventricular fibrillation (VF) complicating early postoperative outcomes. Ca 2+ triggering mechanisms induced by ischemia-reperfusion injury have been implicated as possible causes of this arrhythmia, however, the exact mechanisms remain unclear. The aim of this study was to investigate the role of late sodium current inhibition by ranolazine (RAN) in preventing VF in these patients. Methods: We retrospectively examined 53 patients with aortic stenosis or insufficiency, receiving either
BENTHAM SCIENCE PUBLISHERS eBooks, Nov 16, 2016
European Heart Journal, Aug 1, 2017
Drug treatment 575 verse outcomes was also confirmed by a propensity score-matched analysis, and ... more Drug treatment 575 verse outcomes was also confirmed by a propensity score-matched analysis, and consistent results were obtained in relevant subgroups, with no significant interactions observed between digoxin and sex, history of HF, or valvular heart disease, or concomitant treatment of warfarin in the risk of all-cause death. Conclusions: In Chinese patients with AF, digoxin use was not related to a significantly increased risk of all-cause mortality and cardiovascular death.
Acta Cardiologica, Feb 28, 2009
Progressive electrical alternans followed by conduction block and fibrillatory conduction have be... more Progressive electrical alternans followed by conduction block and fibrillatory conduction have been suggested to precede disorganization of atrial flutter (Afl) to atrial fibrillation (AF). The purpose of the present study was to investigate patterns of local repolarization in the high and low right atrium to determine the site with pronounced propensity to action potential disorganization during Afl and AF. Combination pacing/recording contact monophasic action potential (MAP) catheters were utilized to evaluate repolarization from the upper and low atrial endocardium in 16 pigs. To induce sustained atrial flutter (Afl) or fibrillation (AF), programmed atrial stimulation was carried out prior to and during intravenous acetylcholine (ACh) infusion at a dosage rate of 2.7 mg/min. Atrial repolarization was measured at 30, 50, and 90% of total MAP duration. Two main types of atrial MAPs were distinguished: MAPs originated from high atrial regions showing a prominent notch and longer duration and MAPs recorded from the lower atrium displaying a much slower slope of phase I repolarization and shorter duration. Control stimulation did not elicit any significant atrial tachyarrhythmias. After ACh all animals developed reproducibly induced sustained and non-sustained whole Afl or AF during programmed stimulation. A total of 40 sustained arrhythmia episodes were selected for evaluation: fourteen episodes of primary AF and 26 episodes of Afl. Whole Afl and AF in all animals were associated with MAPs of almost regular morphology in lower parts of atrium and disorganized activation in higher atrial regions. ACh significantly reduced (P < 0.001) both high and low atrial effective refractory periods as well as MAP duration determined at 30, 50, and 90% repolarization. ACh facilitated the induction of Afl more than AF in this experimental model. MAPs recorded from high atrial regions revealed discordant repolarization during Afl or AF, whereas low atrial MAPs maintained their baseline regular morphology. These findings may help expand knowledge about mechanisms underlying instability and perpetuation of these arrhythmias.
Cardiology, 1994
The effects of i.v. diltiazem (0.25 mg/kg) and i.v. verapamil (0.15 mg/kg) were studied in 18 pat... more The effects of i.v. diltiazem (0.25 mg/kg) and i.v. verapamil (0.15 mg/kg) were studied in 18 patients with recurrent paroxysmal supraventricular tachycardia (SVT) who underwent serial electrophysiological studies. In 10 of 18 patients with extranodal accessory pathways the effects of diltiazem and verapamil were similar in comparable plasma concentrations. SVT was prevented in 10/10 cases after diltiazem and 9/10 cases after verapamil, furthermore there as an increase in antegrade refractoriness of the normal AV nodal pathway of 22 and 27%, respectively; accessory pathway refractoriness and conduction remained unchanged in both drugs. In 8 of 18 patients with dual AV nodal pathways diltiazem was significantly less effective as compared to verapamil (p < 0.02) regarding prevention ov SVT (3/8 vs. 8/8 cases) and increase in the antegrade refractoriness of the slow AV nodal pathway (+21 vs. +34%). However, both drugs produced equivalent slowing of antegrade AV nodal conduction and a similar increase in antegrade refractoriness of the fast AV nodal pathway. In all 18 patients, the site of action of both drugs was the antegrade limb, regardless of SVT mechanism. The data suggest that the two calcium antagonists are equipotent in AV reentrance but verapamil may offer greater benefit in AV nodal reentrance than diltiazem.
Cardiovascular Research, Apr 1, 2018
Funding Acknowledgements: The study is supported by Russian Foundation for Basic Research (@ 17-0... more Funding Acknowledgements: The study is supported by Russian Foundation for Basic Research (@ 17-04-00070). Several physiologic substances were identified to potentiate platelet activation induced by primary agonists. Thrombopoietin (TPO) is not only a growth and development factor for the platelet precursor cell, but also can potentiate platelet response to ADP, collagen, thrombin, epinephrine, serotonin, and vasopressin. Nowadays an increasing number of patients may be chronically treated with aspirin alone or in combination with P2Y12 receptor inhibitors prior to acute coronary syndrome manifestation. Surprisingly, several studies identified aspirin pretreatment as an independent risk factor for adverse thrombotic events. Purpose: of the study was to evaluate the impact of antiplatelet pretreatment on platelet priming in patients with ST segment elevation myocardial infarction (STEMI). Materials and methods. We enrolled 40 male patients admitted to ICU due to STEMI. Levels of TPO, stromal cell derived factor 1 (SCD1) and myeloproliferative leukemia virus oncogene (MPL) were measured in plasma samples obtained at admission, on the 2nd and the 7th days since STEMI manifestation with commercially available ELISA kits. Platelet functional testing was performed at admission and on the 7th day by impedance and lumiaggregometry. Results: 33.3% of patients received antiplatelet therapy (23.3% aspirin only) before STEMI manifestation. Those patients with aspirin pretreatment were older (p ¼ 0.049), more likely to be hypertensive. There was no difference in platelet count, PCT or MPV in pretreated and non-pretreated groups. ADP induced platelet aggregation at admission was significantly suppressed by prior aspirin treatment: 0.0 (0.0 ;4.0) vs 2.0 (1.0; 7.0) Ohm, p ¼ 0.031. All patients revealed moderately to significantly elevated TPO levels at admission with no differences in those with and without pretreatment: 264.82 (153.32; 337.64) vs 256.49 (161.17; 299.41) pg/mL, p ¼ 0.869. In aspirin naïve patients TPO dynamics was of U-shape with significant reduction on the 2nd day, compared to aspirin pretreated patients (p ¼ 0.047). "Monotonous" profiles of TPO were associated with significantly higher levels of secreted ATP in ADP stimulated platelets: 0.42 (0.2; 0.8) vs 0.16 (0.0; 0.33) nmole, p ¼ 0.03. Moderate to strong negative correlations between TPO, SCD1, MPL and collagen, but not ADP induced platelet aggregation and secretion were detected. Conclusion. Aspirin pretreatment significantly modifies thrombopoietin profiles in STEMI patients. Platelet functional heterogeneity in patients with STEMI is deepened through unequal exposure to platelet primers.
The Journal of innovations in cardiac rhythm management, Mar 1, 2021
Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation ... more Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation in intact animals; however, its efficacy in the setting of atrial tachycardia (AT) is unknown. The purpose of this study was to investigate the effects of RAN alone or in combination with amiodarone (AMIO) on rapid pacing-evoked right AT in rabbit hearts. Right atrial monophasic action potentials (MAPs) were recorded in 11 anesthetized rabbits, using combination MAP pacing catheters. Vulnerability to AT was tested by employing consecutive trains of rapid burst pacing prior to and after 2.4 mg/kg of RAN alone delivered intravenously and then in combination with 3 mg/kg of AMIO as a 15-minute infusion. Primary endpoints were postdrug AT reproducibility as well as cycle length (CL) and tachycardia duration. MAP duration at 75% repolarization and the effective refractory period (ERP) were assessed during programmed pacing to calculate the atrial postrepolarization refractoriness (aPRR = ERP-MAPD 75%). AT was elicited in eight out of 11 rabbits; only these animals were included for further investigation. RAN did not abolish the inducibility of AT in any experiment; however, it prolonged its CL (baseline vs. RAN: 120 ± 16 ms vs. 138 ± 18 ms; p = 0.053). Supplemental AMIO further increased the AT CL (baseline vs. RAN + AMIO: 120 ± 16 ms vs. 152 ± 23 ms; p = 0.006), without affecting arrhythmia reinducibility. Slowing of the tachycardia after RAN or RAN + AMIO was associated with spontaneous termination of the arrhythmia. RAN prolonged the aPRR significantly, while AMIO in addition to RAN potentiated this effect. Neither RAN alone nor its combination with AMIO abolished the elicitation of AT in this model. However, both agents synergistically prolonged the aPRR, resulting in the slowing of AT and promoting spontaneous termination of the arrhythmia.
Journal of surgery and research, 2020
Objectives: Cardiac surgery has been reported to be associated, albeit rarely, with postoperative... more Objectives: Cardiac surgery has been reported to be associated, albeit rarely, with postoperative vision alterations up to vision loss. In this study, we sought to examine if patients undergoing on-pump cardiac surgery are at higher risk for developing deranged vision based on analysis of standard visual parameters. Methods: A total of 88 patients, who underwent coronary artery bypass graft (CABG, n=56) or aortic valve replacement (AVR, n=32) surgery were initially enrolled in our study in order to assess their visual function, right before and one month after surgery. The following examinations were performed: Visual Acquity (VA), Intraocular Pressure (IOP), Fundus
Journal of Molecular and Cellular Cardiology, 1986
In these studies, wfi have used K+-sensitive plunge electrode (0.25 mm dia) measurements to exami... more In these studies, wfi have used K+-sensitive plunge electrode (0.25 mm dia) measurements to examine the influence of extracellular K + concentration gradients on the incidence of vent~icular fibrillation (VF) in coronary ]igated rat hearts. The results (see table) revealed that as the perfusate K + was decreased, there was a progressive increase in the incidence and rate of appearance of VF.
Cardiology, 1989
The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyar... more The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyarrhythmias were studied by programmed electrical stimulation in 15 dogs, 4-8 days after myocardial infarction. Recordings from the infarcted and normal anterior wall of the left ventricle were obtained with an epicardial implanted 'composite' electrode. Bepridil (5 mg/kg) or nifedipine (0.025 mg/kg) were administered i.v. on different days and testing was repeated. Sustained ventricular tachycardia was prevented or significantly slowed by bepridil in 11/12 experiments compared with none of 9 experiments with nifedipine. Paradoxically, in 10/15 dogs nifedipine accelerated arrhythmias or even provoked ventricular fibrillation. Bepridil prolonged refractoriness of infarcted myocardium by 15 +/- 4% (mean +/- SD, p less than 0.01), which was greater than the increase it produced in the effective refractory period of normal tissue (9.0 +/- 3.8%) or QTc interval (11 +/- 5.5%). In contrast, nifedipine significantly shortened these parameters. Both drugs did not influence conduction in infarcted and normal zones as indicated by unchanged late potentials, QRS duration and normal-zone electrograms, respectively. The data indicate that the antiarrhythmic action of bepridil was predominantly related to the prolongation of ventricular refractoriness and repolarization (class III effects).
European Heart Journal, Mar 1, 1988
Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and,... more Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and, therefore, allow the scintigraphic detection of myocardial infarction. In order to provide a constant supply of myosin-specific antibodies, the somatic cell fusion technique was used for the selection and propagation of AM Ab. Out of 126 antibody producing cell lines, nine were selected for further subcloning, due to their high affinity for purified myosin. For the in vivo imaging, two IgG-antibody molecules appeared particularly useful based on their antigenic specificity as assessed by immunoblotting and indirect immunofluorescence technique. After radiolabelling with iodine-123, undigested antibody molecules or their Fab fragments were injected into 10 dogs with experimental myocardial infarction. The accumulation of radioactivity in myocardial infarction was assessed by in vivo imaging and in vitro scintigraphy of ventricular slices stained by tetrazolium. The use of undigested AM Ab resulted in a high uptake ratio of radioactivity in the infarcted as compared to normal myocardium (20:1). In vivo infarct imaging, however, was not possible due to sustained labelling of the blood pool. The uptake ratio of iodine-123 labelled Fab fragments was only 9:1, but due to a faster plasma clearance of the Fab fragments, uptake in the heart could be visualized 5 h after intravenous injection. Clear differentiation between infarcted and noninfarcted myocardium, however, was limited by accumulation of radioactivity in the thoracotomy wound, in the liver, and in the stomach.
Cardiovascular Drugs and Therapy, Aug 1, 1995
Myocardial infarction was produced in 27 anesthetized dogs by ligating the left anterior descendi... more Myocardial infarction was produced in 27 anesthetized dogs by ligating the left anterior descending (LAD) coronary artery proximal to the septal branch. Nineteen of these animals survived the operation and were studied by programmed stimulation in a random sequence between the third and seventh days after the infarct. Complete electrophysiologic testing was implemented in each animal prior to and after single doses of either alinidine (1 mg/kg IV) or zatebradine (0.5 mg/kg IV). Alinidine prevented reinduction of sustained ventricular tachycardia (SVT) in only 2 of 9 dogs and zatebradine in 1 of 8 dogs. The SVT cycle length was not significantly changed in all cases in which it was still inducible despite drug administration (p > 0.05). Alinidine lengthened the effective refractory period (ERP) in the AV node (p < 0.01), whereas zatebradine did not induce a statistically significant prolongation. Conversely, zatebradine increased the left ventricular ERP, while alinidine left it almost unchanged. The rate-corrected QT interval (QTc) did not significantly differ from control values after the administration of either agents. Also, the duration and the ERP of infarctzone potentials, defined as late potentials, remained unaltered. The results indicate that the bradycardic agents alinidine and zatebradine do not exert antiarrhythmic efficacy against SVT induced during subacute myocardial infarction in conscious dogs. None of these drugs substantially changed ventricular electrophysiology or showed a drug-specific proarrhythmic effect.
Cardiology, 1992
In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after ... more In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs.
Your article is protected by copyright and all rights are held exclusively by Springer Science+Bu... more Your article is protected by copyright and all rights are held exclusively by Springer Science+Business Media, LLC, part of Springer Nature. This e-offprint is for personal use only and shall not be self-archived in electronic repositories. If you wish to selfarchive your article, please use the accepted manuscript version for posting on your own website. You may further deposit the accepted manuscript version in any repository, provided it is only made publicly available 12 months after official publication or later and provided acknowledgement is given to the original source of publication and a link is inserted to the published article on Springer's website. The link must be accompanied by the following text: "The final publication is available at link.springer.com".
Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation ... more Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation in intact animals; however, its efficacy in the setting of atrial tachycardia (AT) is unknown. The purpose of this study was to investigate the effects of RAN alone or in combination with amiodarone (AMIO) on rapid pacing-evoked right AT in rabbit hearts. Right atrial monophasic action potentials (MAPs) were recorded in 11 anesthetized rabbits, using combination MAP pacing catheters. Vulnerability to AT was tested by employing consecutive trains of rapid burst pacing prior to and after 2.4 mg/kg of RAN alone delivered intravenously and then in combination with 3 mg/kg of AMIO as a 15-minute infusion. Primary endpoints were postdrug AT reproducibility as well as cycle length (CL) and tachycardia duration. MAP duration at 75% repolarization and the effective refractory period (ERP) were assessed during programmed pacing to calculate the atrial postrepolarization refractoriness (aPRR = ERP-MAPD 75%). AT was elicited in eight out of 11 rabbits; only these animals were included for further investigation. RAN did not abolish the inducibility of AT in any experiment; however, it prolonged its CL (baseline vs. RAN: 120 ± 16 ms vs. 138 ± 18 ms; p = 0.053). Supplemental AMIO further increased the AT CL (baseline vs. RAN + AMIO: 120 ± 16 ms vs. 152 ± 23 ms; p = 0.006), without affecting arrhythmia reinducibility. Slowing of the tachycardia after RAN or RAN + AMIO was associated with spontaneous termination of the arrhythmia. RAN prolonged the aPRR significantly, while AMIO in addition to RAN potentiated this effect. Neither RAN alone nor its combination with AMIO abolished the elicitation of AT in this model. However, both agents synergistically prolonged the aPRR, resulting in the slowing of AT and promoting spontaneous termination of the arrhythmia.
The involvement of the autonomic nervous system in the pathogenesis of ventricular arrhythmias ha... more The involvement of the autonomic nervous system in the pathogenesis of ventricular arrhythmias has stimulated interest in studying alterations of the cardiac innervation in experimental models of myocardial infarction. Enhanced sympathetic activation can occasionally trigger ventricular tachycardias in subjects having normal hearts [17, 27]; however, such arrhythmias are frequently provoked under myocardial ischaemia [32]. The arrhythmogenic potential of sympathetic hyperactivity was shown to be mediated by left-sided nerves or ganglia; their stimulation during acute myocardial ischaemia led to malignant arrhythmias including ventricular fibrillation [26, 29, 30].
PubMed, Feb 28, 2014
The impact of ranolazine, an anti-ishemic agent with antiarrhythmic properties, on paroxysmal atr... more The impact of ranolazine, an anti-ishemic agent with antiarrhythmic properties, on paroxysmal atrial fibrillation (PAF) in patients with coronary artery disease (CAD) remains unclear. Pacing devices can be useful tools for disclosing even asymptomatic PAF. Purpose of this study is to assess the effect of ranolazine on atrial fibrillation (AF), in patients with CAD, PAF and a dual-chamber pacemaker. We studied 74 patients with CAD, PAF, and sick sinus syndrome or atrio-ventricular block, treated with pacemakers capable to detect PAF episodes. The total time in AF, AF burden, and the number of PAF episodes within the last 6 months before enrolment in the study, mean AF duration per episode, and the QTc interval were initially assessed. Subsequently, patients were randomized into additional treatment with ranolazine (375 mg twice daily) or placebo. Following six months of treatment, all parameters were reassessed and compared to those before treatment. Ranolazine was associated with shorter total AF duration (81.56±45.24 hours versus 68.71±34.84 hours, p=0.002), decreased AF burden (1.89±1.05% versus 1.59±0.81%, p=0.002), and shortened mean AF duration (1.15±0.41 hours versus 0.92±0.35 hours, p=0.01). In the placebo group no such differences were observed. In both groups, no significant differences in the number of PAF episodes and QTc duration were observed. We conclude that in patients with CAD and PAF, ranolazine reduces the total time in AF, AF burden, and mean AF duration. These findings may imply additional antiarrhythmic properties of ranolazine on atrial myocardium and might indicate the necessity of its use in ischemic patients with PAF.
Journal of surgery and research, 2020
Objectives: Aortic valve replacement (AVR) is often associated with intraoperative ventricular fi... more Objectives: Aortic valve replacement (AVR) is often associated with intraoperative ventricular fibrillation (VF) complicating early postoperative outcomes. Ca 2+ triggering mechanisms induced by ischemia-reperfusion injury have been implicated as possible causes of this arrhythmia, however, the exact mechanisms remain unclear. The aim of this study was to investigate the role of late sodium current inhibition by ranolazine (RAN) in preventing VF in these patients. Methods: We retrospectively examined 53 patients with aortic stenosis or insufficiency, receiving either
BENTHAM SCIENCE PUBLISHERS eBooks, Nov 16, 2016
European Heart Journal, Aug 1, 2017
Drug treatment 575 verse outcomes was also confirmed by a propensity score-matched analysis, and ... more Drug treatment 575 verse outcomes was also confirmed by a propensity score-matched analysis, and consistent results were obtained in relevant subgroups, with no significant interactions observed between digoxin and sex, history of HF, or valvular heart disease, or concomitant treatment of warfarin in the risk of all-cause death. Conclusions: In Chinese patients with AF, digoxin use was not related to a significantly increased risk of all-cause mortality and cardiovascular death.
Acta Cardiologica, Feb 28, 2009
Progressive electrical alternans followed by conduction block and fibrillatory conduction have be... more Progressive electrical alternans followed by conduction block and fibrillatory conduction have been suggested to precede disorganization of atrial flutter (Afl) to atrial fibrillation (AF). The purpose of the present study was to investigate patterns of local repolarization in the high and low right atrium to determine the site with pronounced propensity to action potential disorganization during Afl and AF. Combination pacing/recording contact monophasic action potential (MAP) catheters were utilized to evaluate repolarization from the upper and low atrial endocardium in 16 pigs. To induce sustained atrial flutter (Afl) or fibrillation (AF), programmed atrial stimulation was carried out prior to and during intravenous acetylcholine (ACh) infusion at a dosage rate of 2.7 mg/min. Atrial repolarization was measured at 30, 50, and 90% of total MAP duration. Two main types of atrial MAPs were distinguished: MAPs originated from high atrial regions showing a prominent notch and longer duration and MAPs recorded from the lower atrium displaying a much slower slope of phase I repolarization and shorter duration. Control stimulation did not elicit any significant atrial tachyarrhythmias. After ACh all animals developed reproducibly induced sustained and non-sustained whole Afl or AF during programmed stimulation. A total of 40 sustained arrhythmia episodes were selected for evaluation: fourteen episodes of primary AF and 26 episodes of Afl. Whole Afl and AF in all animals were associated with MAPs of almost regular morphology in lower parts of atrium and disorganized activation in higher atrial regions. ACh significantly reduced (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) both high and low atrial effective refractory periods as well as MAP duration determined at 30, 50, and 90% repolarization. ACh facilitated the induction of Afl more than AF in this experimental model. MAPs recorded from high atrial regions revealed discordant repolarization during Afl or AF, whereas low atrial MAPs maintained their baseline regular morphology. These findings may help expand knowledge about mechanisms underlying instability and perpetuation of these arrhythmias.
Cardiology, 1994
The effects of i.v. diltiazem (0.25 mg/kg) and i.v. verapamil (0.15 mg/kg) were studied in 18 pat... more The effects of i.v. diltiazem (0.25 mg/kg) and i.v. verapamil (0.15 mg/kg) were studied in 18 patients with recurrent paroxysmal supraventricular tachycardia (SVT) who underwent serial electrophysiological studies. In 10 of 18 patients with extranodal accessory pathways the effects of diltiazem and verapamil were similar in comparable plasma concentrations. SVT was prevented in 10/10 cases after diltiazem and 9/10 cases after verapamil, furthermore there as an increase in antegrade refractoriness of the normal AV nodal pathway of 22 and 27%, respectively; accessory pathway refractoriness and conduction remained unchanged in both drugs. In 8 of 18 patients with dual AV nodal pathways diltiazem was significantly less effective as compared to verapamil (p < 0.02) regarding prevention ov SVT (3/8 vs. 8/8 cases) and increase in the antegrade refractoriness of the slow AV nodal pathway (+21 vs. +34%). However, both drugs produced equivalent slowing of antegrade AV nodal conduction and a similar increase in antegrade refractoriness of the fast AV nodal pathway. In all 18 patients, the site of action of both drugs was the antegrade limb, regardless of SVT mechanism. The data suggest that the two calcium antagonists are equipotent in AV reentrance but verapamil may offer greater benefit in AV nodal reentrance than diltiazem.
Cardiovascular Research, Apr 1, 2018
Funding Acknowledgements: The study is supported by Russian Foundation for Basic Research (@ 17-0... more Funding Acknowledgements: The study is supported by Russian Foundation for Basic Research (@ 17-04-00070). Several physiologic substances were identified to potentiate platelet activation induced by primary agonists. Thrombopoietin (TPO) is not only a growth and development factor for the platelet precursor cell, but also can potentiate platelet response to ADP, collagen, thrombin, epinephrine, serotonin, and vasopressin. Nowadays an increasing number of patients may be chronically treated with aspirin alone or in combination with P2Y12 receptor inhibitors prior to acute coronary syndrome manifestation. Surprisingly, several studies identified aspirin pretreatment as an independent risk factor for adverse thrombotic events. Purpose: of the study was to evaluate the impact of antiplatelet pretreatment on platelet priming in patients with ST segment elevation myocardial infarction (STEMI). Materials and methods. We enrolled 40 male patients admitted to ICU due to STEMI. Levels of TPO, stromal cell derived factor 1 (SCD1) and myeloproliferative leukemia virus oncogene (MPL) were measured in plasma samples obtained at admission, on the 2nd and the 7th days since STEMI manifestation with commercially available ELISA kits. Platelet functional testing was performed at admission and on the 7th day by impedance and lumiaggregometry. Results: 33.3% of patients received antiplatelet therapy (23.3% aspirin only) before STEMI manifestation. Those patients with aspirin pretreatment were older (p ¼ 0.049), more likely to be hypertensive. There was no difference in platelet count, PCT or MPV in pretreated and non-pretreated groups. ADP induced platelet aggregation at admission was significantly suppressed by prior aspirin treatment: 0.0 (0.0 ;4.0) vs 2.0 (1.0; 7.0) Ohm, p ¼ 0.031. All patients revealed moderately to significantly elevated TPO levels at admission with no differences in those with and without pretreatment: 264.82 (153.32; 337.64) vs 256.49 (161.17; 299.41) pg/mL, p ¼ 0.869. In aspirin naïve patients TPO dynamics was of U-shape with significant reduction on the 2nd day, compared to aspirin pretreated patients (p ¼ 0.047). "Monotonous" profiles of TPO were associated with significantly higher levels of secreted ATP in ADP stimulated platelets: 0.42 (0.2; 0.8) vs 0.16 (0.0; 0.33) nmole, p ¼ 0.03. Moderate to strong negative correlations between TPO, SCD1, MPL and collagen, but not ADP induced platelet aggregation and secretion were detected. Conclusion. Aspirin pretreatment significantly modifies thrombopoietin profiles in STEMI patients. Platelet functional heterogeneity in patients with STEMI is deepened through unequal exposure to platelet primers.
The Journal of innovations in cardiac rhythm management, Mar 1, 2021
Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation ... more Ranolazine (RAN) has previously been shown to lower the onset of cholinergic atrial fibrillation in intact animals; however, its efficacy in the setting of atrial tachycardia (AT) is unknown. The purpose of this study was to investigate the effects of RAN alone or in combination with amiodarone (AMIO) on rapid pacing-evoked right AT in rabbit hearts. Right atrial monophasic action potentials (MAPs) were recorded in 11 anesthetized rabbits, using combination MAP pacing catheters. Vulnerability to AT was tested by employing consecutive trains of rapid burst pacing prior to and after 2.4 mg/kg of RAN alone delivered intravenously and then in combination with 3 mg/kg of AMIO as a 15-minute infusion. Primary endpoints were postdrug AT reproducibility as well as cycle length (CL) and tachycardia duration. MAP duration at 75% repolarization and the effective refractory period (ERP) were assessed during programmed pacing to calculate the atrial postrepolarization refractoriness (aPRR = ERP-MAPD 75%). AT was elicited in eight out of 11 rabbits; only these animals were included for further investigation. RAN did not abolish the inducibility of AT in any experiment; however, it prolonged its CL (baseline vs. RAN: 120 ± 16 ms vs. 138 ± 18 ms; p = 0.053). Supplemental AMIO further increased the AT CL (baseline vs. RAN + AMIO: 120 ± 16 ms vs. 152 ± 23 ms; p = 0.006), without affecting arrhythmia reinducibility. Slowing of the tachycardia after RAN or RAN + AMIO was associated with spontaneous termination of the arrhythmia. RAN prolonged the aPRR significantly, while AMIO in addition to RAN potentiated this effect. Neither RAN alone nor its combination with AMIO abolished the elicitation of AT in this model. However, both agents synergistically prolonged the aPRR, resulting in the slowing of AT and promoting spontaneous termination of the arrhythmia.
Journal of surgery and research, 2020
Objectives: Cardiac surgery has been reported to be associated, albeit rarely, with postoperative... more Objectives: Cardiac surgery has been reported to be associated, albeit rarely, with postoperative vision alterations up to vision loss. In this study, we sought to examine if patients undergoing on-pump cardiac surgery are at higher risk for developing deranged vision based on analysis of standard visual parameters. Methods: A total of 88 patients, who underwent coronary artery bypass graft (CABG, n=56) or aortic valve replacement (AVR, n=32) surgery were initially enrolled in our study in order to assess their visual function, right before and one month after surgery. The following examinations were performed: Visual Acquity (VA), Intraocular Pressure (IOP), Fundus
Journal of Molecular and Cellular Cardiology, 1986
In these studies, wfi have used K+-sensitive plunge electrode (0.25 mm dia) measurements to exami... more In these studies, wfi have used K+-sensitive plunge electrode (0.25 mm dia) measurements to examine the influence of extracellular K + concentration gradients on the incidence of vent~icular fibrillation (VF) in coronary ]igated rat hearts. The results (see table) revealed that as the perfusate K + was decreased, there was a progressive increase in the incidence and rate of appearance of VF.
Cardiology, 1989
The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyar... more The effects of the two calcium antagonists bepridil and nifedipine on induced ventricular tachyarrhythmias were studied by programmed electrical stimulation in 15 dogs, 4-8 days after myocardial infarction. Recordings from the infarcted and normal anterior wall of the left ventricle were obtained with an epicardial implanted 'composite' electrode. Bepridil (5 mg/kg) or nifedipine (0.025 mg/kg) were administered i.v. on different days and testing was repeated. Sustained ventricular tachycardia was prevented or significantly slowed by bepridil in 11/12 experiments compared with none of 9 experiments with nifedipine. Paradoxically, in 10/15 dogs nifedipine accelerated arrhythmias or even provoked ventricular fibrillation. Bepridil prolonged refractoriness of infarcted myocardium by 15 +/- 4% (mean +/- SD, p less than 0.01), which was greater than the increase it produced in the effective refractory period of normal tissue (9.0 +/- 3.8%) or QTc interval (11 +/- 5.5%). In contrast, nifedipine significantly shortened these parameters. Both drugs did not influence conduction in infarcted and normal zones as indicated by unchanged late potentials, QRS duration and normal-zone electrograms, respectively. The data indicate that the antiarrhythmic action of bepridil was predominantly related to the prolongation of ventricular refractoriness and repolarization (class III effects).
European Heart Journal, Mar 1, 1988
Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and,... more Radiolabelled anti-myosin antibodies (AM Ab) specifically accumulate in necrotizing myocytes and, therefore, allow the scintigraphic detection of myocardial infarction. In order to provide a constant supply of myosin-specific antibodies, the somatic cell fusion technique was used for the selection and propagation of AM Ab. Out of 126 antibody producing cell lines, nine were selected for further subcloning, due to their high affinity for purified myosin. For the in vivo imaging, two IgG-antibody molecules appeared particularly useful based on their antigenic specificity as assessed by immunoblotting and indirect immunofluorescence technique. After radiolabelling with iodine-123, undigested antibody molecules or their Fab fragments were injected into 10 dogs with experimental myocardial infarction. The accumulation of radioactivity in myocardial infarction was assessed by in vivo imaging and in vitro scintigraphy of ventricular slices stained by tetrazolium. The use of undigested AM Ab resulted in a high uptake ratio of radioactivity in the infarcted as compared to normal myocardium (20:1). In vivo infarct imaging, however, was not possible due to sustained labelling of the blood pool. The uptake ratio of iodine-123 labelled Fab fragments was only 9:1, but due to a faster plasma clearance of the Fab fragments, uptake in the heart could be visualized 5 h after intravenous injection. Clear differentiation between infarcted and noninfarcted myocardium, however, was limited by accumulation of radioactivity in the thoracotomy wound, in the liver, and in the stomach.
Cardiovascular Drugs and Therapy, Aug 1, 1995
Myocardial infarction was produced in 27 anesthetized dogs by ligating the left anterior descendi... more Myocardial infarction was produced in 27 anesthetized dogs by ligating the left anterior descending (LAD) coronary artery proximal to the septal branch. Nineteen of these animals survived the operation and were studied by programmed stimulation in a random sequence between the third and seventh days after the infarct. Complete electrophysiologic testing was implemented in each animal prior to and after single doses of either alinidine (1 mg/kg IV) or zatebradine (0.5 mg/kg IV). Alinidine prevented reinduction of sustained ventricular tachycardia (SVT) in only 2 of 9 dogs and zatebradine in 1 of 8 dogs. The SVT cycle length was not significantly changed in all cases in which it was still inducible despite drug administration (p > 0.05). Alinidine lengthened the effective refractory period (ERP) in the AV node (p < 0.01), whereas zatebradine did not induce a statistically significant prolongation. Conversely, zatebradine increased the left ventricular ERP, while alinidine left it almost unchanged. The rate-corrected QT interval (QTc) did not significantly differ from control values after the administration of either agents. Also, the duration and the ERP of infarctzone potentials, defined as late potentials, remained unaltered. The results indicate that the bradycardic agents alinidine and zatebradine do not exert antiarrhythmic efficacy against SVT induced during subacute myocardial infarction in conscious dogs. None of these drugs substantially changed ventricular electrophysiology or showed a drug-specific proarrhythmic effect.
Cardiology, 1992
In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after ... more In 12 open-chest dogs, cardiac sympathetic nervous activity (CSNA) was recorded before and after occlusion of the left anterior descending coronary artery as well as during reperfusion and ventricular fibrillation (VF). In 7 control animals, CSNA did not significantly differ from preocclusion levels when determined 20 min after occlusion (+3.5 +/- 1.5%, mean +/- SEM) and up to 15 min following reperfusion (+1.5 +/- 0.6%). However, VF was associated with a potential increase in CSNA by 106 +/- 15.5% (p less than 0.001). The effect of lidocaine (6 mg/kg) on cardiac sympathetic tone was examined in 5 additional animals. Lidocaine reduced control CSNA by 23 +/- 4.7% (p less than 0.001); subsequent ischemia and reperfusion did not substantially change the level of preocclusion activity. CSNA decreased significantly also during VF (52 +/- 4.2%, p less than 0.001). In conclusion, efferent CSNA was slightly altered in the course of acute myocardial ischemia and reperfusion, but significantly increased during VF. Lidocaine produced marked attenuation of CSNA in anesthetized dogs.