Pathophysiology of arrhythmias: Clinical electrophysiology

Zipes, Douglas P.; Heger, James J.; Prystowsky, Eric N.

doi:10.1016/0002-8703(83)90004-2

Cited by 9 publications

(3 citation statements)

References 75 publications

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“…30,31 Both electrophysiological and anatomical characteristics such as slow conduction, unstable APD, fibrosis, and compact scar are known to facilitate reentry. [32][33][34][35][36][37] Risks for reentry become higher when any nonspecific action of pharmacological intervention alters these parameters. Therefore, these engineered cardiac tissues showing reentry (Fig.…”

Section: Discussionmentioning

confidence: 99%

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues

Munarin

Kaiser

Kim

et al. 2017

Tissue Engineering Part C: Methods

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Rapid prototyping and fabrication of elastomeric molds for sterile culture of engineered tissues allow for the development of tissue geometries that can be tailored to different in vitro applications and customized as implantable scaffolds for regenerative medicine. Commercially available molds offer minimal capabilities for adaptation to unique conditions or applications versus those for which they are specifically designed. Here we describe a replica molding method for the design and fabrication of poly(dimethylsiloxane) (PDMS) molds from laser-etched acrylic negative masters with ∼0.2 mm resolution. Examples of the variety of mold shapes, sizes, and patterns obtained from laser-etched designs are provided. We use the patterned PDMS molds for producing and culturing engineered cardiac tissues with cardiomyocytes derived from human-induced pluripotent stem cells. We demonstrate that tight control over tissue morphology and anisotropy results in modulation of cell alignment and tissue-level conduction properties, including the appearance and elimination of reentrant arrhythmias, or circular electrical activation patterns. Techniques for handling engineered cardiac tissues during implantation in vivo in a rat model of myocardial infarction have been developed and are presented herein to facilitate development and adoption of surgical techniques for use with hydrogel-based engineered tissues. In summary, the method presented herein for engineered tissue mold generation is straightforward and low cost, enabling rapid design iteration and adaptation to a variety of applications in tissue engineering. Furthermore, the burden of equipment and expertise is low, allowing the technique to be accessible to all.

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Section: Discussionmentioning

confidence: 99%

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues

Munarin

Kaiser

Kim

et al. 2017

Tissue Engineering Part C: Methods

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show abstract

“…In the transition phase, this rapid activation impinges upon differential refractory periods in atrioventricular nodal tissue, and leading to unidirectional block [13]. AVNRT then enters the maintenance phase, characterized by classical reentry [14]. Clinically, catheter-based therapies for AVNRT target the maintenance phase of the arrhythmia via ablation of the slow pathway, resulting in excellent long-term success [15].…”

Section: Temporal Evolution Of Af Mechanismsmentioning

confidence: 99%

Mechanisms Underlying AF: Triggers, Rotors, Other?

Krummen

Hebsur

Salcedo

et al. 2015

Curr Treat Options Cardio Med

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Opinion statement There is ongoing debate regarding the precise mechanisms underlying atrial fibrillation (AF). An improved understanding of these mechanisms is urgently needed to improve interventional strategies to suppress and eliminate AF, since the success of current strategies is suboptimal. At present, guidelines for AF ablation focus on pulmonary vein (PV) isolation for the prevention of arrhythmia. Additional targets are presently unclear, and include additional linear ablation and electrogram-guided substrate modification, without clear mechanistic relevance. PV and non-PV triggers are likely central in the first few seconds of AF initiation. Rapid activation from such triggers interacts with transitional mechanisms including conduction velocity slowing, action potential duration (APD) alternans, and steep APD restitution to cause conduction block and initiate functional reentry. However, complete suppression of potential triggers has proven elusive, and the intra-procedural mapping and targeting of transitional mechanisms has not been reported. A growing body of research implicates electrical rotors and focal sources as central mechanisms for the maintenance of AF. In several recent series, they were observed in nearly all patients with sustained arrhythmia. Ablation of rotor and focal source sites, prior to pulmonary vein isolation, substantially modulated atrial fibrillation in a high proportion of patients, and improved ablation outcomes versus pulmonary vein isolation alone. These results have subsequently been confirmed in multicenter series, and the improved outcomes have been found to persist to a mean follow-up of 3 years. Recently, rotors have been observed by multiple groups using diverse technologies. These findings represent a paradigm shift in AF, focusing on sustaining mechanisms, as is currently done with other arrhythmias such as atrioventricular node reentrant tachycardia. Studies are currently underway to assess the optimal strategy for the application of rotor-based ablation in AF management, including clinical trials on the relative efficacy of rotor-only ablation versus PVI-only ablation, which will inform future practice guidelines.

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“…[18][19][20] A significant relationship has been reported in many pathophysiological conditions between autonomic nervous system imbalance and cardiovascular mortality, including sudden cardiac death. [21][22][23] Some studies have shown that cardiac autonomic tone could be altered in patients with myocardial infarction 24,25 and heart failure 26 undergoing percutaneous transluminal coronary angioplasty. 27 Sympathovagal imbalance is also a common finding in diabetes and the usefulness of standard cardiovascular tests in assessment of cardiac autonomic neuropathy in diabetes is well documented.…”

Section: Research Papermentioning

confidence: 99%

Autonomic nervous system and cardiovascular risk assessment during one year of growth hormone (GH) replacement therapy in adults with GH deficiency

Boschetti¹,

Casu²,

Moretti³

et al. 2014

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oBJecTIve: This prospective study aimed to evaluate the impact of growth hormone deficiency (gHd) on cardiac autonomic tone and on cardiovascular risk and the changes after 12 months of gH replacement therapy (gHrT). gHd is associated with increased cardiovascular morbidity and mortality. This has been attributed to increased markers of cardiovascular risk and to abnormalities of both the cardiac and peripheral autonomic nervous systems. The autonomic cardiac nervous system (AcNs) can be indirectly evaluated by analysis of heart rate variability (Hrv) in clinostatism and orthostatism. desIgN: We compared 14 gHd patients at baseline and after 12 months of gHrT and 17 healthy controls. We analyzed a number of cardiovascular risk factors and we used analysis of Hrv during the Tilt Test that identified high frequency (HF) and low frequency (lF), representing parasympathetic and sympathetic activity, respectively. resUlTs: compared with the control group, in either clinostatism or in orthostatism our patients showed a significantly lower value of lF (P=0.047; P=0.004, respectively), whereas HF was significantly reduced in orthostatism (P=0.037), and indicatively in clinostatism (P=0.065). These values remained unchanged after 12 months of gHrT. No statistically significant differences were found between the lF/HF ratio in untreated and treated patients. In gHd patients, there was a significant reduction of cardiovascular risk in 12 months of replacement therapy (P=0.002). coNclUsIoNs: our study highlights the absence of sympathovagal imbalance in gHd patients; gHrT does not change AcNs during the first year of gH treatment but it reduces the absolute cardiovascular risk in these patients.

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Pathophysiology of arrhythmias: Clinical electrophysiology

Cited by 9 publications

References 75 publications

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues

Laser-Etched Designs for Molding Hydrogel-Based Engineered Tissues

Mechanisms Underlying AF: Triggers, Rotors, Other?

Autonomic nervous system and cardiovascular risk assessment during one year of growth hormone (GH) replacement therapy in adults with GH deficiency

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