Evolution and Resolution of Long-term Cardiac Memory

Shvilkin, Alexei; Danilo, Peter; Wang, Jie; Burkhoff, Daniel; Anyukhovsky, Evgeny P.; Sosunov, Eugene A.; Hara, Motoki; Rosen, Michael R.

doi:10.1161/01.cir.97.18.1810

Cited by 109 publications

(106 citation statements)

References 29 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, we have previously shown that the statistically insignificant variations in sinus rate occurring before and after pacing cannot be the cause of these T-wave changes. 21 The action potentials we recorded are entirely consistent with results from earlier isolated tissue studies in that the notch of the epicardial action potential in T-wave memory is smaller than in controls. 6 In short-term pacing, however, the epicardial APD did not manifest the prolongation seen with long-term pacing and cardiac memory in our present or previous study.…”

Section: Discussionsupporting

confidence: 89%

“…unassociated with cardiac failure 21 or hypertrophy (cell capacitance, reflecting cell size, is unchanged) provides longterm T-wave changes that render the study of disaggregated myocytes practicable. Moreover, we have previously shown that the statistically insignificant variations in sinus rate occurring before and after pacing cannot be the cause of these T-wave changes.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory

et al. 1999

Self Cite

View full text Add to dashboard Cite

Background-Cardiac memory refers to an altered T-wave morphology induced by ventricular pacing or arrhythmias that persist for variable intervals after resumption of sinus rhythm. Methods and Results-We induced long-term cardiac memory (LTM) in conscious dogs by pacing the ventricles at 120 bpm for 3 weeks. ECGs were recorded daily for 1 hour, during which time pacing was discontinued. At terminal study, the heart was removed and the electrophysiology of left ventricular epicardial myocytes was investigated. Control (C) and LTM ECG did not differ, except for T-wave amplitude, which decreased from 0.12Ϯ0.18 to Ϫ0.34Ϯ0.21 mV (ϮSEM, PϽ0.05), and T-wave vector, which shifted from Ϫ37Ϯ12°to Ϫ143Ϯ4°(PϽ0.05). Epicardial action potentials revealed loss of the notch and lengthening of duration at 20 days (both PϽ0.05). Calcium-insensitive transient outward current (I to ) was investigated by whole-cell patch clamp. No difference in capacitance was seen in C and LTM myocytes. I to activated on membrane depolarization to Ϫ25Ϯ1 mV in C and Ϫ7Ϯ1 mV (PϽ0.05) in LTM myocytes, indicating a positive voltage shift of activation. I to density was reduced in LTM myocytes, and a decreased mRNA level for Kv4.3 was observed. Recovery of I to from inactivation was significantly prolonged: it was 531Ϯ80 ms (nϭ10) in LTM and 27Ϯ6 ms (nϭ9) in C (PϽ0.05) at Ϫ65 mV. Conclusions-I to changes are associated with and can provide at least a partial explanation for action-potential and T-wave changes occurring with LTM. (Circulation. 1999;99:1898-1905.)

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory

et al. 1999

Self Cite

View full text Add to dashboard Cite

show abstract

“…These results suggest that other ionic currents play an important role in electrical remodeling. 60 Rubart et al 56 reported a prolonged APD and a reduced notch after one hour of ventricular pacing in dogs. They found a reduction in I to as well as an increase in peak I Ca,L .…”

Section: What Triggers Electrical Remodeling?mentioning

confidence: 99%

“…Kä a¨b et al 27 hypothesized that downregulation of I to is at least partially responsible for the prolongation of the APD. Shvilkin et al 60 observed APD prolongation in both epicardium (which has large I to ) and endocardium (which has small I to ), and no change in APD in midmyocardium (which has prominent I to ). These results suggest that other ionic currents play an important role in electrical remodeling.…”

Section: What Triggers Electrical Remodeling?mentioning

confidence: 99%

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

et al. 2008

View full text Add to dashboard Cite

Abstract-Regional variation in ionic membrane currents causes differences in action potential duration (APD) and is proarrhythmic. After several weeks of ventricular pacing, AP morphology and duration are changed due to electrical remodeling of the transient outward potassium current (I to ) and the L-type calcium current (I Ca,L ). It is not clear what mechanism drives electrical remodeling. By modeling the cardiac muscle as a string of segments that are electrically and mechanically coupled, we investigate the hypothesis that electrical remodeling is triggered by changes in mechanical load. Contractile force generated by the sarcomeres depends on the calcium transient and on the sarcomere length. Stroke work is determined for each segment by simulating the cardiac cycle. Electrical remodeling is simulated by adapting I Ca,L kinetics such that a homogeneous distribution of stroke work is obtained. With electrical remodeling, a more homogeneous shortening of the fiber is obtained, while heterogeneity in APD increases and the repolarization wave reverses. Our results are in agreement with experimentally observed homogeneity in mechanics and heterogeneity in electrophysiology. In conclusion, electrical remodeling is a possible mechanism to reduce heterogeneity in cardiomechanics induced by ventricular pacing.

show abstract

“…6 In an additional parallel, cardiac memory also appears to exhibit both short-term and long-term forms, with the latter being directly dependent on protein synthesis. 10 This distinction between short and long-term memory is potentially useful when considering the underlying mechanisms.…”

Section: Cardiac Memorymentioning

confidence: 99%

Mechanisms linking short- and long-term electrical remodeling in the heart .....is it a stretch?

Marrus

Nerbonne²

2008

Channels

View full text Add to dashboard Cite

Ion channels play a central role in the normal electro-mechanical functioning of the heart and are implicated in a variety of disease processes. In response to electrical or mechanical perturbations, cardiac myocytes exhibit remarkable changes in the expression and/or the function of sarcolemmal ion channels, a process that is broadly described as electrical remodeling. This remodeling has beneficial, as well as adverse, effects on myocardial function, including increased risk of fatal arrhythmias. One specific example of cardiac electrical remodeling is cardiac memory, a phenomenon induced in the heart following abnormal myocardial activation patterns produced by artificial pacemakers. Recent studies have shed new light on the molecular mechanisms underlying cardiac memory and suggest intriguing parallels between cardiac memory and heart failure. In both situations, abnormal mechanical stretch of the myocardium results in direct alterations in ion channel properties, as well as in the activation of angiotensin-dependent signaling cascades. With time, altered gene transcription and protein synthesis lead to persistent changes in ion channel levels and activities, changes that can significantly impact normal cardiac function and increase arrhythmia susceptibility.

show abstract

Evolution and Resolution of Long-term Cardiac Memory

Cited by 109 publications

References 29 publications

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

Mechanisms linking short- and long-term electrical remodeling in the heart .....is it a stretch?

Contact Info

Product

Resources

About

Evolution and Resolution of Long-term Cardiac Memory

Cited by 109 publications

References 29 publications

Transient Outward Current, I to1 , Is Altered in Cardiac Memory

Transient Outward Current, I to1 , Is Altered in Cardiac Memory

Mechanoelectric Feedback as a Trigger Mechanism for Cardiac Electrical Remodeling: A Model Study

Mechanisms linking short- and long-term electrical remodeling in the heart .....is it a stretch?

Contact Info

Product

Resources

About

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory

Transient Outward Current, I _to1 , Is Altered in Cardiac Memory