scholarly journals Effect of activation sequence on transmural patterns of repolarization and action potential duration in rabbit ventricular myocardium

2010 ◽  
Vol 299 (6) ◽  
pp. H1812-H1822 ◽  
Author(s):  
Rachel C. Myles ◽  
Olivier Bernus ◽  
Francis L. Burton ◽  
Stuart M. Cobbe ◽  
Godfrey L. Smith
Keyword(s):  
Action Potential ◽  
Action Potential Duration ◽  
Single Cells ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Isolated Cells ◽  
Electrophysiological Properties ◽  
Relative Contribution ◽  
Rabbit Ventricular Myocardium ◽  
Transmural Heterogeneity

Although transmural heterogeneity of action potential duration (APD) is established in single cells isolated from different tissue layers, the extent to which it produces transmural gradients of repolarization in electrotonically coupled ventricular myocardium remains controversial. The purpose of this study was to examine the relative contribution of intrinsic cellular gradients of APD and electrotonic influences to transmural repolarization in rabbit ventricular myocardium. Transmural optical mapping was performed in left ventricular wedge preparations from eight rabbits. Transmural patterns of activation, repolarization, and APD were recorded during endocardial and epicardial stimulation. Experimental results were compared with modeled data during variations in electrotonic coupling. A transmural gradient of APD was evident during endocardial stimulation, which reflected differences previously seen in isolated cells, with the longest APD at the endocardium and the shortest at the epicardium (endo: 165 ± 5 vs. epi: 147 ± 4 ms; P < 0.05). During epicardial stimulation, this gradient reversed (epi: 162 ± 4 vs. endo: 148 ± 6 ms; P < 0.05). In both activation sequences, transmural repolarization followed activation and APD shortened along the activation path such that significant transmural gradients of repolarization did not occur. This correlation between transmural activation time and APD was recapitulated in simulations and varied with changes in intercellular coupling, confirming that it is mediated by electrotonic current flow between cells. These data suggest that electrotonic influences are important in determining the transmural repolarization sequence in rabbit ventricular myocardium and that they are sufficient to overcome intrinsic differences in the electrophysiological properties of the cells across the ventricular wall.

Rate-dependent shortening of action potential duration increases ventricular vulnerability in failing rabbit heart

2011 ◽  
Vol 300 (2) ◽  
pp. H565-H573 ◽  
Author(s):  
Masahide Harada ◽  
Yukiomi Tsuji ◽  
Yuko S. Ishiguro ◽  
Hiroki Takanari ◽  
Yusuke Okuno ◽  
...  
Keyword(s):  
Action Potential ◽  
High Frequency ◽  
Rabbit Heart ◽  
Left Ventricular ◽  
High Frequency Stimulation ◽  
Electrophysiological Properties ◽  
Rate Dependent ◽  
Frequency Stimulation ◽  
And Control

Congestive heart failure (CHF) predisposes to ventricular fibrillation (VF) in association with electrical remodeling of the ventricle. However, much remains unknown about the rate-dependent electrophysiological properties in a failing heart. Action potential properties in the left ventricular subepicardial muscles during dynamic pacing were examined with optical mapping in pacing-induced CHF ( n = 18) and control ( n = 17) rabbit hearts perfused in vitro. Action potential durations (APDs) in CHF were significantly longer than those observed for controls at basic cycle lengths (BCLs) >1,000 ms but significantly shorter at BCLs <400 ms. Spatial APD dispersions were significantly increased in CHF versus control (by 17–81%), and conduction velocity was significantly decreased in CHF (by 6–20%). In both groups, high-frequency stimulation (BCLs <150 ms) always caused spatial APD alternans; spatially concordant alternans and spatially discordant alternans (SDA) were induced at 60% and 40% in control, respectively, whereas 18% and 82% in CHF. SDA in CHF caused wavebreaks followed by reentrant excitations, giving rise to VF. Incidence of ventricular tachycardia/VFs elicited by high-frequency dynamic pacing (BCLs <150 ms) was significantly higher in CHF versus control (93% vs. 20%). In CHF, left ventricular subepicardial muscles show significant APD shortenings at short BCLs favoring reentry formations following wavebreaks in association with SDA. High-frequency excitation itself may increase the vulnerability to VF in CHF.

Hypertensive-diabetic cardiomyopathy in rats

1990 ◽  
Vol 258 (3) ◽  
pp. H793-H805 ◽  
Author(s):  
F. S. Fein ◽  
B. E. Zola ◽  
A. Malhotra ◽  
S. Cho ◽  
S. M. Factor ◽  
...  
Keyword(s):  
Action Potential ◽  
Right Ventricular ◽  
Action Potential Duration ◽  
Stimulus Frequency ◽  
Negative Inotropic Effect ◽  
Left Ventricular ◽  
Resting Membrane Potential ◽  
Contraction And Relaxation ◽  
And Control ◽  
Myocardial Pathology

Left ventricular papillary muscle function, transmembrane action potentials, myosin adenosinetriphosphatase (ATPase) and isoenzyme distribution, and myocardial pathology were studied in hypertensive (H), diabetic (D), hypertensive-diabetic (HD), and control (C) rats. There was approximately 50% relative left ventricular hypertrophy in H and HD rats. Relative lung and liver weights were greater in HD rats. Peak velocity of shortening tended to decrease progressively in H, D, and HD rats. The duration of contraction and relaxation was markedly prolonged in Ds and HDs. The length-developed tension relation was blunted in HDs. The negative inotropic effect of verapamil was similar in all groups. Resting membrane potential and amplitude were decreased in D and HD rats. Action potential duration was increased in H, D, and especially HD rats. The shortening of action potential duration with increased stimulus frequency was greater in H, D, and especially HD rats than in Cs. Left ventricular myosin ATPase and V1 isoenzyme content decreased progressively in H, D, and HD rats. Right ventricular V1 isoenzyme content was not affected in H rats but was markedly decreased in D and HD rats. Left (and right) ventricular pathology was unchanged in rats with diabetes but was increased in rats with hypertension. These data suggest that the combination of myocardial pathology (due to hypertension) and cellular dysfunction (caused mainly by diabetes) may result in cardiomyopathy and congestive heart failure in the HD rat.

Regression of LV hypertrophy with captopril normalizes membrane currents in rabbits

1998 ◽  
Vol 275 (4) ◽  
pp. H1216-H1224 ◽  
Author(s):  
Seth J. Rials ◽  
Xiaoping Xu ◽  
Ying Wu ◽  
Roger A. Marinchak ◽  
Peter R. Kowey
Keyword(s):  
Cell Membrane ◽  
Action Potential ◽  
Renal Artery ◽  
Current Density ◽  
Action Potential Duration ◽  
Left Ventricular ◽  
Membrane Current ◽  
Membrane Capacitance ◽  
Membrane Currents ◽  
Cell Membrane Capacitance

Recent studies indicate that regression of left ventricular hypertrophy (LVH) normalizes the in situ electrophysiological abnormalities of the left ventricle. This study was designed to determine whether regression of LVH also normalizes the abnormalities of individual membrane currents. LVH was induced in rabbits by renal artery banding. Single ventricular myocytes from rabbits with LVH at 3 mo after renal artery banding demonstrated increased cell membrane capacitance, prolonged action potential duration, decreased inward rectifier K+ current density, and increased transient outward K+ current density compared with myocytes from age-matched controls. Additional rabbits were randomized at 3 mo after banding to treatment with either vehicle or captopril for an additional 3 mo. Myocytes from LVH rabbits treated with vehicle showed persistent membrane current abnormalities. However, myocytes isolated from LVH rabbits treated with captopril had normal cell membrane capacitance, action potential duration, and membrane current densities. Captopril had no direct effect on membrane currents of either control or LVH myocytes. These data support the hypothesis that the action potential prolongation and membrane current abnormalities of LVH are reversed by regression. Normalization of membrane currents probably explains the reduced vulnerability to ventricular arrhythmia observed in this LVH model after treatment with captopril.

scholarly journals Key pathways associated with heart failure development revealed by gene networks correlated with cardiac remodeling

2008 ◽  
Vol 35 (3) ◽  
pp. 222-230 ◽  
Author(s):  
Zhong Gao ◽  
Andreas S. Barth ◽  
Deborah DiSilvestre ◽  
Fadi G. Akar ◽  
Yanli Tian ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Action Potential ◽  
Action Potential Duration ◽  
Expression Patterns ◽  
Left Ventricular ◽  
Ventricular Pacing ◽  
Extracellular Matrix Components ◽  
Transcriptional Changes ◽  
Rapid Ventricular Pacing

Heart failure (HF) is the leading cause of morbidity and mortality in the industrialized world. While the transcriptomic changes in end-stage failing myocardium have received much attention, no information is available on the gene expression patterns associated with the development of HF in large mammals. Therefore, we used a well-controlled canine model of tachycardia-induced HF to examine global gene expression in left ventricular myocardium with Affymetrix canine oligonucleotide arrays at various stages after initiation of rapid ventricular pacing ( days 3, 7, 14, and 21). The gene expression data were complemented with measurements of action potential duration, conduction velocity, and left ventricular end diastolic pressure, and dP/d t(max) over the time course of rapid ventricular pacing. As a result, we present a phenotype-centered gene association network, defining molecular systems that correspond temporally to hemodynamic and electrical remodeling processes. Gene Ontology analysis revealed an orchestrated regulation of oxidative phosphorylation, ATP synthesis, cell signaling pathways, and extracellular matrix components, which occurred as early as 3 days after the initiation of ventricular pacing, coinciding with the early decline in left ventricular pump function and prolongation of action potential duration. The development of clinically overt left ventricular dysfunction was associated with few additional changes in the myocardial transcriptome. We conclude that the majority of tachypacing-induced transcriptional changes occur early after initiation of rapid ventricular pacing. As the transition to overt HF is characterized by few additional transcriptional changes, posttranscriptional modifications may be more critical in regulating myocardial structure and function during later stages of HF.

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