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Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload

View Article: PubMed Central - PubMed

ABSTRACT

Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis.

No MeSH data available.


Related in: MedlinePlus

Epicardial activation patterns of the left ventricle during electrical pacing. Representative activation maps constructed at 2 ms intervals from the LV mid-portion lateral wall (field of view 8 × 8 mm) are shown for each group. Pacing cycle length is 300 ms in all cases. Asterisk indicates the site or pacing, bidirectional arrows the direction of maximal and minimal conduction velocity. Scale bar 5 mm. The graph below shows correlation between the maximal and minimal conduction velocity and phenotype severity. r, Pearson's correlation coefficient. Line represents linear regression.
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Figure 2: Epicardial activation patterns of the left ventricle during electrical pacing. Representative activation maps constructed at 2 ms intervals from the LV mid-portion lateral wall (field of view 8 × 8 mm) are shown for each group. Pacing cycle length is 300 ms in all cases. Asterisk indicates the site or pacing, bidirectional arrows the direction of maximal and minimal conduction velocity. Scale bar 5 mm. The graph below shows correlation between the maximal and minimal conduction velocity and phenotype severity. r, Pearson's correlation coefficient. Line represents linear regression.

Mentions: The data was band-pass filtered and processed using a 3 × 3 median filter to reduce noise. Action potential duration at 50 and 90% of amplitude was then measured from the recordings in several representative subregions of each heart. The first derivative was then numerically calculated, and its peak was used to detect pixel activation time. Spatio-temporal activation maps (Figure 2) were then constructed in the BV_Ana software (SciMedia, Japan). Using this software, longitudinal (maximal) and transverse (minimal) conduction velocity was measured, along the prevailing long and short axis of subepicardial myocytes as defined in rodents (Morley and Vaidya, 2001). Anisotropy was defined as the ratio between the transverse (CVmin) and longitudinal (CVmax) conduction velocity.


Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
Epicardial activation patterns of the left ventricle during electrical pacing. Representative activation maps constructed at 2 ms intervals from the LV mid-portion lateral wall (field of view 8 × 8 mm) are shown for each group. Pacing cycle length is 300 ms in all cases. Asterisk indicates the site or pacing, bidirectional arrows the direction of maximal and minimal conduction velocity. Scale bar 5 mm. The graph below shows correlation between the maximal and minimal conduction velocity and phenotype severity. r, Pearson's correlation coefficient. Line represents linear regression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4997968&req=5

Figure 2: Epicardial activation patterns of the left ventricle during electrical pacing. Representative activation maps constructed at 2 ms intervals from the LV mid-portion lateral wall (field of view 8 × 8 mm) are shown for each group. Pacing cycle length is 300 ms in all cases. Asterisk indicates the site or pacing, bidirectional arrows the direction of maximal and minimal conduction velocity. Scale bar 5 mm. The graph below shows correlation between the maximal and minimal conduction velocity and phenotype severity. r, Pearson's correlation coefficient. Line represents linear regression.
Mentions: The data was band-pass filtered and processed using a 3 × 3 median filter to reduce noise. Action potential duration at 50 and 90% of amplitude was then measured from the recordings in several representative subregions of each heart. The first derivative was then numerically calculated, and its peak was used to detect pixel activation time. Spatio-temporal activation maps (Figure 2) were then constructed in the BV_Ana software (SciMedia, Japan). Using this software, longitudinal (maximal) and transverse (minimal) conduction velocity was measured, along the prevailing long and short axis of subepicardial myocytes as defined in rodents (Morley and Vaidya, 2001). Anisotropy was defined as the ratio between the transverse (CVmin) and longitudinal (CVmax) conduction velocity.

View Article: PubMed Central - PubMed

ABSTRACT

Volume overload leads to development of eccentric cardiac hypertrophy and heart failure. In our previous report, we have shown myocyte hypertrophy with no fibrosis and decrease in gap junctional coupling via connexin43 in a rat model of aorto-caval fistula at 21 weeks. Here we set to analyze the electrophysiological and protein expression changes in the left ventricle and correlate them with phenotypic severity based upon ventricles to body weight ratio. ECG analysis showed increased amplitude and duration of the P wave, prolongation of PR and QRS interval, ST segment elevation and decreased T wave amplitude in the fistula group. Optical mapping showed a prolongation of action potential duration in the hypertrophied hearts. Minimal conduction velocity (CV) showed a bell-shaped curve, with a significant increase in the mild cases and there was a negative correlation of both minimal and maximal CV with heart to body weight ratio. Since the CV is influenced by gap junctional coupling as well as the autonomic nervous system, we measured the amounts of tyrosine hydroxylase (TH) and choline acetyl transferase (ChAT) as a proxy for sympathetic and parasympathetic innervation, respectively. At the protein level, we confirmed a significant decrease in total and phosphorylated connexin43 that was proportional to the level of hypertrophy, and similarly decreased levels of TH and ChAT. Even at a single time-point, severity of morphological phenotype correlates with progression of molecular and electrophysiological changes, with the most hypertrophied hearts showing the most severe changes that might be related to arrhythmogenesis.

No MeSH data available.


Related in: MedlinePlus