Theofilos M Kolettis | University of Ioannina/Greece (original) (raw)

Papers by Theofilos M Kolettis

Life

Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurrin... more Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth understanding of the underlying mechanisms. Sympathetic activation has long been known to play a key role in the pathophysiology of ischemia-induced arrhythmias, but the regulating factors remain under investigation. Several lines of evidence implicate the endothelin system (a family of three isopeptides and two specific receptors) as an important modulator of sympathetic activation in the setting of acute coronary syndromes. Such interaction is present in the heart and in the adrenal medulla, whereas less is known on the effects of the endothelin system on the central autonomic network. This article summarizes the current state-of-the-art, placing emphasis on early-phase arrhythmogenesis, and highlights potential areas of future research.

Journal of Cardiovascular Development and Disease, May 21, 2021

Journal of Cardiovascular Development and Disease, 2021

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous corona... more Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden.

Journal of Cardiovascular Development and Disease, 2021

Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of ... more Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of β-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, cu...

Journal of Cardiovascular Development and Disease, 2021

Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of exce... more Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of excessive sympathetic activation is established in this process, concurrent vagal responses have not been adequately described. Moreover, it remains unclear whether autonomic activity depends on the mode of delivery. Here, we explored the hypothesis that the different management of cesarean and vaginal delivery may elicit diverse responses affecting both autonomic arms. For this aim, continuous electrocardiographic recording was performed in 20 women during labor, and non-invasive indices of sympathetic and vagal activity were compared between the two modes of delivery. We report sympathetic prevalence during cesarean delivery, caused by marked vagal withdrawal, whereas autonomic activity was rather stable during vaginal delivery. These differences may be attributed to the effects of anesthesia during cesarean delivery, along with the protective effects of oxytocin administration during vagi...

International Journal of Molecular Sciences, 2020

Myocardial infarction remains a major health-related problem with significant acute and long-term... more Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models ha...

Physiological Research, 2019

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis ar... more Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3±8.9 s), when compared to controls (546.2±130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin re...

Journal of basic and clinical physiology and pharmacology, Jan 26, 2018

Background Autonomic responses participate in the pathophysiology of acute myocardial infarction,... more Background Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. Methods The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. Results In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhyt...

Journal of Arrhythmia, 2017

American Heart Journal, Apr 1, 1994

ABSTRACT

Current pharmaceutical design

Frontiers in Cardiovascular Medicine, 2015

Hellenic journal of cardiology : HJC = Hellēnikē kardiologikē epitheōrēsē

Pulmonary hypertension portends an adverse outcome. Animal models have improved current understan... more Pulmonary hypertension portends an adverse outcome. Animal models have improved current understanding of the complex pathophysiology of the disease, but may be technically demanding. Moreover, plexiform vascular lesions are rarely observed, limiting the extrapolation to human pathophysiology. The aim of the present study was first, to assess the feasibility of closed-chest pressure recordings, and mainly, to further characterise a new model of endothelin receptor-B deficient rats. Jugular venous catheterisation was assessed in 15 Wistar rats. Pressure recordings via a left lateral thoracotomy and histological findings were compared in three rat groups (age 20 +/- 1 weeks, weight 200-250 g): (a) wild type (n = 10, group A); (b) wild type after monocrotaline injection (n=10, group B); and (c) endothelin receptor-B deficient rats (n = 10, group C) after monocrotaline injection. Pressure recordings via the jugular approach were feasible in only 3 (20%) rats. Compared to group A, there w...

International journal of clinical and experimental medicine, Jan 23, 2010

The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension i... more The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the effects of T9429, an antibody against transforming growth factor-β receptors, on hemodynamic, histological and functional parameters in the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats (268±10g) via an osmotic mini-pump for 7 days. One week thereafter, right ventricular systolic pressure, pulmonary vascular remodeling and exercise tolerance were evaluated. Compared to the monocrotaline group (25.5±1.9mmHg), right ventricular systolic pressure was lower (p=0.0014) in the monocrotaline+antibody group (18.4±0.8mmHg). This was translated into attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155) exercise duration (2.08±0.29min versus 6.19±1.02min). Pulmonary arterial wall thickness (in vessels 5...

Life

Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurrin... more Despite the contemporary treatment of acute coronary syndromes, arrhythmic complications occurring prior to medical attendance remain significant, mandating in-depth understanding of the underlying mechanisms. Sympathetic activation has long been known to play a key role in the pathophysiology of ischemia-induced arrhythmias, but the regulating factors remain under investigation. Several lines of evidence implicate the endothelin system (a family of three isopeptides and two specific receptors) as an important modulator of sympathetic activation in the setting of acute coronary syndromes. Such interaction is present in the heart and in the adrenal medulla, whereas less is known on the effects of the endothelin system on the central autonomic network. This article summarizes the current state-of-the-art, placing emphasis on early-phase arrhythmogenesis, and highlights potential areas of future research.

Journal of Cardiovascular Development and Disease, May 21, 2021

Journal of Cardiovascular Development and Disease, 2021

Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous corona... more Patients with ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI) may demonstrate distal microvascular embolization of thrombotic materials. We retrospectively examined 20 cases displaying extensive thrombus in the infarct-related artery (IRA), treated either with a two-step procedure, with interim tirofiban infusion, or immediate stent implantation. Distal embolization tended to be more common in the latter strategy, but, overall, the outcome was comparable. Thus, a two-staged procedure may be considered in selected cases of primary PCI associated with high thrombus burden.

Journal of Cardiovascular Development and Disease, 2021

Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of ... more Myocardial infarction often leads to progressive structural and electrophysiologic remodeling of the left ventricle. Despite the widespread use of β-adrenergic blockade and implantable defibrillators, morbidity and mortality from chronic-phase ventricular tachyarrhythmias remains high, calling for further investigation on the underlying pathophysiology. Histological and functional studies have demonstrated extensive alterations of sympathetic nerve endings at the peri-infarct area and flow-innervation mismatches that create a highly arrhythmogenic milieu. Such accumulated evidence, along with the previously well-documented autonomic dysfunction as an important contributing factor, has stirred intense research interest for pharmacologic and non-pharmacologic neuromodulation in post-infarction heart failure. In this regard, aldosterone inhibitors, sacubitril/valsartan and sodium-glucose cotransporter type 2 inhibitors have shown antiarrhythmic effects. Non-pharmacologic modalities, cu...

Journal of Cardiovascular Development and Disease, 2021

Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of exce... more Takotsubo syndrome is a serious complication of labor. Although the pathophysiologic role of excessive sympathetic activation is established in this process, concurrent vagal responses have not been adequately described. Moreover, it remains unclear whether autonomic activity depends on the mode of delivery. Here, we explored the hypothesis that the different management of cesarean and vaginal delivery may elicit diverse responses affecting both autonomic arms. For this aim, continuous electrocardiographic recording was performed in 20 women during labor, and non-invasive indices of sympathetic and vagal activity were compared between the two modes of delivery. We report sympathetic prevalence during cesarean delivery, caused by marked vagal withdrawal, whereas autonomic activity was rather stable during vaginal delivery. These differences may be attributed to the effects of anesthesia during cesarean delivery, along with the protective effects of oxytocin administration during vagi...

International Journal of Molecular Sciences, 2020

Myocardial infarction remains a major health-related problem with significant acute and long-term... more Myocardial infarction remains a major health-related problem with significant acute and long-term consequences. Acute coronary occlusion results in marked electrophysiologic alterations that can induce ventricular tachyarrhythmias such as ventricular tachycardia or ventricular fibrillation, often heralding sudden cardiac death. During the infarct-healing stage, hemodynamic and structural changes can lead to left ventricular dilatation and dysfunction, whereas the accompanying fibrosis forms the substrate for re-entrant circuits that can sustain ventricular tachyarrhythmias. A substantial proportion of such patients present clinically with overt heart failure, a common disease-entity associated with high morbidity and mortality. Several lines of evidence point toward a key role of the growth hormone/insulin-like growth factor-1 axis in the pathophysiology of post-infarction structural and electrophysiologic remodeling. Based on this rationale, experimental studies in animal models ha...

Physiological Research, 2019

Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis ar... more Endothelin alters central sympathetic responses, but the resultant effects on arrhythmogenesis are unknown. We examined ventricular tachyarrhythmias after endothelin receptor-A blockade in the brain of Wistar rats with acute myocardial infarction. For this aim, BQ-123 (n=6) or phosphate-buffered saline (n=6) were injected intracerebroventricularly. After 10 min, the left coronary artery was ligated, followed by implantation of telemetry transmitters. Electrocardiography and voluntary activity (as a surrogate of acute left ventricular failure) were continuously monitored for 24 h. Infarct-size was similar in the two groups. There were fewer episodes of ventricular tachyarrhythmias of shorter average duration in treated rats, leading to markedly shorter total duration (12.3±8.9 s), when compared to controls (546.2±130.3 s). Voluntary activity increased in treated rats during the last hours of recording, but bradyarrhythmic episodes were comparable between the two groups. Endothelin re...

Journal of basic and clinical physiology and pharmacology, Jan 26, 2018

Background Autonomic responses participate in the pathophysiology of acute myocardial infarction,... more Background Autonomic responses participate in the pathophysiology of acute myocardial infarction, but their precise time course remains unclear. Here, we investigated the autonomic activity and ventricular tachyarrhythmias in conscious, unrestrained rats post-infarction. Methods The left coronary artery was ligated in 12 Wistar rats, and six rats were sham operated, followed by 24-h electrocardiographic recording via implanted telemetry transmitters. Sympathetic activity was assessed by detrended fluctuation analysis and vagal activity by time- and frequency-domain analysis of heart rate variability. The duration of the ventricular tachyarrhythmias was measured, and voluntary motion served as a marker of heart failure. Results In sham-operated rats, heart rate and sympathetic activity remained low, whereas vagal activity rose progressively after the fourth hour. Post-ligation, medium-sized antero-septal necrosis was observed, reaching ~20% of the left ventricular volume; tachyarrhyt...

Journal of Arrhythmia, 2017

American Heart Journal, Apr 1, 1994

ABSTRACT

Current pharmaceutical design

Frontiers in Cardiovascular Medicine, 2015

Hellenic journal of cardiology : HJC = Hellēnikē kardiologikē epitheōrēsē

Pulmonary hypertension portends an adverse outcome. Animal models have improved current understan... more Pulmonary hypertension portends an adverse outcome. Animal models have improved current understanding of the complex pathophysiology of the disease, but may be technically demanding. Moreover, plexiform vascular lesions are rarely observed, limiting the extrapolation to human pathophysiology. The aim of the present study was first, to assess the feasibility of closed-chest pressure recordings, and mainly, to further characterise a new model of endothelin receptor-B deficient rats. Jugular venous catheterisation was assessed in 15 Wistar rats. Pressure recordings via a left lateral thoracotomy and histological findings were compared in three rat groups (age 20 +/- 1 weeks, weight 200-250 g): (a) wild type (n = 10, group A); (b) wild type after monocrotaline injection (n=10, group B); and (c) endothelin receptor-B deficient rats (n = 10, group C) after monocrotaline injection. Pressure recordings via the jugular approach were feasible in only 3 (20%) rats. Compared to group A, there w...

International journal of clinical and experimental medicine, Jan 23, 2010

The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension i... more The role of transforming growth factor-β in the pathogenesis of pulmonary arterial hypertension is unclear. We examined the effects of T9429, an antibody against transforming growth factor-β receptors, on hemodynamic, histological and functional parameters in the rat model of monocrotaline-induced pulmonary hypertension. One week after monocrotaline injection (60 mg/kg) in 28 Wistar rats, T9429 (0.1mg/kg daily) was administered intraperito-neally in 19 rats (268±10g) via an osmotic mini-pump for 7 days. One week thereafter, right ventricular systolic pressure, pulmonary vascular remodeling and exercise tolerance were evaluated. Compared to the monocrotaline group (25.5±1.9mmHg), right ventricular systolic pressure was lower (p=0.0014) in the monocrotaline+antibody group (18.4±0.8mmHg). This was translated into attenuated right ventricular hypertrophy (p=0.0063) and longer (p=0.0155) exercise duration (2.08±0.29min versus 6.19±1.02min). Pulmonary arterial wall thickness (in vessels 5...