Unique Properties of Cardiac Action Potentials Recorded with Voltage‐Sensitive Dyes

Girouard, Steven D.; Laurita., R Kenneth; Rosenbaum, David S.

doi:10.1111/j.1540-8167.1996.tb00478.x

Cited by 189 publications

(181 citation statements)

References 39 publications

Supporting

Mentioning

173

Contrasting

Order By: Relevance

“…Conduction velocity was measured by averaging local velocity vectors from contiguous sites transverse and longitudinal to cardiac fibers. Action potential duration (APD) was measured as the time of activation to 70% repolarization, and action potential rise time was corrected for optical blurring as described previously (32).…”

Section: Methodsmentioning

confidence: 99%

Targeted Activation of c-Jun N-terminal Kinase in Vivo Induces Restrictive Cardiomyopathy and Conduction Defects

Petrich

Eloff

Lerner

et al. 2004

Journal of Biological Chemistry

Self Cite

105

View full text Add to dashboard Cite

The stress-activated protein kinase, c-Jun N-terminal kinase (JNK), has been implicated in the process of cardiac hypertrophy and apoptosis, yet the specific roles of JNK in heart failure are unclear. To determine the effects of JNK activation in intact heart, we established transgenic animals using a Cre/loxP-mediated gene switch approach to achieve targeted expression of an upstream activator, mitogen-activated protein kinase kinase 7 (D) (MKK7D), in ventricular myocytes. MKK7D expression led to significant JNK activation, robust induction of the fetal gene program, and contractile dysfunction. The animals died ϳ7 weeks after birth with signs of congestive heart failure. Doppler mode echocardiography revealed a marked stiffening of JNK-activated hearts that was associated with the remodeling of specific extracellular matrix components. Gene expression analysis of MKK7D hearts revealed up-regulation of transforming growth factor ␤ signaling, offering a potential molecular mechanism underlying changes in extracellular matrix composition. In addition, we demonstrated that JNK activation led to specific loss of connexin 43 protein and gap junctions without affecting the expression or localization of other key intercalated disc proteins. This specific and localized gap junction remodeling resulted in significant slowing of ventricular electrical conduction in JNK-activated hearts. These results represent the first characterization of JNK-mediated cardiac pathology in vivo and support an important role for JNK signaling in specific aspects of cardiac remodeling in the pathogenesis of cardiac disease.

show abstract

Section: Methodsmentioning

confidence: 99%

Targeted Activation of c-Jun N-terminal Kinase in Vivo Induces Restrictive Cardiomyopathy and Conduction Defects

Petrich

Eloff

Lerner

et al. 2004

Journal of Biological Chemistry

Self Cite

105

View full text Add to dashboard Cite

show abstract

“…17,19,24 Briefly, to make quantitative measurements of action potential characteristics, including depolarization and repolarization, our optical mapping system was designed to record high-fidelity action potentials simultaneously from 128 sites on the intact heart. In the present study, an optical magnification of 1.8ϫ was used, corresponding to a mapping field of 1 cm 2 and 0.83-mm spatial resolution between recording sites.…”

Section: Optical Mapping Systemmentioning

confidence: 99%

Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart

et al. 1998

Self Cite

View full text Add to dashboard Cite

Background-Previously, we have shown that a premature stimulus can significantly modulate spatial gradients of ventricular repolarization (ie, modulated dispersion), which result from heterogeneous electrophysiological properties between cells. The role modulated dispersion may play in determining electrical instability in the heart is unknown. Methods and Results-To determine if premature stimulus-induced changes in repolarization are a mechanism that governs susceptibility to cardiac arrhythmias, optical action potentials were recorded simultaneously from 128 ventricular sites (1 cm 2 ) in 8 Langendorff-perfused guinea pig hearts. After baseline pacing (S 1 ), a single premature stimulus (S 2 ) was introduced over a range of S 1 S 2 coupling intervals. Arrhythmia vulnerability after each premature stimulus was determined by measurement of a modified ventricular fibrillation threshold (VFT) during the T wave of each S 2 beat (ie, S 2 -VFT). As the S 1 S 2 interval was shortened to an intermediate value, spatial gradients of repolarization and vulnerability to fibrillation decreased by 51Ϯ9% (meanϮSEM) and 73Ϯ45%, respectively, compared with baseline levels. As the S 1 S 2 interval was further shortened, repolarization gradients increased above baseline levels by 54Ϯ30%, which was paralleled by a corresponding increase (37Ϯ8%) in vulnerability.Conclusions-These data demonstrate that modulation of repolarization gradients by a single premature stimulus significantly influences vulnerability to ventricular fibrillation. This may represent a novel mechanism for the formation of arrhythmogenic substrates during premature stimulation of the heart. (Circulation. 1998;98:2774-2780.)

show abstract

“…As previously described, action potential activation time was defined as the point of maximum positive first derivative for the action potential upstroke, and repolarization time was defined as the point of maximum positive second derivative of the repolarization phase. 25, 30 Action potential duration (APD) was measured as the time between activation time and repolarization time.…”

Section: Discussionmentioning

confidence: 99%

Arrhythmogenic Delayed Afterdepolarizations Are Promoted by Severe Hypothermia But Not Therapeutic Hypothermia

Fukaya

Piktel

Wan

et al. 2018

Circ J

View full text Add to dashboard Cite

ryanodine receptor (RyR) dysfunction. 16-18 Given clinical observations of increased ventricular ectopy and irritability during SH, frequent triggered arrhythmias would be predicted. 10,19,20 Moreover, although repolarization abnormalities induced by hypothermia are known to promote substrates for re-entrant VF, 21 the effect of hypothermia on VF triggers is poorly understood.Despite the contrast in arrhythmia susceptibility associated with TH vs. SH, there have been very few systematic studies that have investigated the underlying arrhythmia mechanisms. Existing data on the effect of hypothermia on Ca dysregulation and triggered activity is difficult to interpret because many studies have been performed at temperatures even colder than those observed during SH (e.g., room temperature) and in varied species. 22,23 Moreover, the effect of hypothermia on cellular Ca regulation is complex, such that the net impact on susceptibility to arrhythmias is difficult to predict. Therefore, we aimed to investigate the effects of clinically relevant temperatures on Ca dysregulation and triggered arrhythmias in a single animal model at the tissue, cellular and subcellular level. We hypothesized T herapeutic hypothermia (TH) improves neurologic outcomes and survival in patients with return of spontaneous circulation (ROSC) after cardiac arrest. 1,2 Current cardiopulmonary resuscitation guidelines recommend that all comatose patients with ROSC should be cooled to have temperature maintained between 32 and 36°C for 24 h. 3-6 In addition to improving neurological outcomes, several recent experimental and clinical studies 7-9 suggest that TH decreases infarct size in acute myocardial infarction. Importantly, the incidence of lethal arrhythmias in post-resuscitated patients treated with TH is relatively low, 1,4,10 suggesting that temperatures used in clinical TH may be antiarrhythmic, although this is controversial. 11- 13 Unlike TH, severe hypothermia (SH, less than 30°C), is well known to be pro-arrhythmic. Arrhythmias in patients with accidental SH are common and include ventricular fibrillation (VF), which can be refractory to standard therapy. 14,15 Experimental studies have shown that hypothermia causes dysregulation of cellular calcium (Ca), which has been associated with intracellular Ca overload and Background: Severe hypothermia (SH) is known to be arrhythmogenic, but the effect of therapeutic hypothermia (TH) on arrhythmias is unclear. It is hypothesized that susceptibility to Ca-mediated arrhythmia triggers would be increased only by SH.

show abstract

Unique Properties of Cardiac Action Potentials Recorded with Voltage‐Sensitive Dyes

Cited by 189 publications

References 39 publications

Targeted Activation of c-Jun N-terminal Kinase in Vivo Induces Restrictive Cardiomyopathy and Conduction Defects

Targeted Activation of c-Jun N-terminal Kinase in Vivo Induces Restrictive Cardiomyopathy and Conduction Defects

Modulated Dispersion Explains Changes in Arrhythmia Vulnerability During Premature Stimulation of the Heart

Arrhythmogenic Delayed Afterdepolarizations Are Promoted by Severe Hypothermia But Not Therapeutic Hypothermia

Contact Info

Product

Resources

About