Limits...
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.


Longitudinal changes in MAO expression in the ACF model. Western blot was performed with samples from left ventricles of animals with ACF and sham-operated animals (animals sacrificed 8, 16, 24, and 51 weeks after creation of ACF). Each sample represents a pooled tissue homogenate from five animals from the individual group. Samples were loaded in duplicates on the 10% minigels. As a primary antibody rabbit anti-monoamine oxidase A was used (MAO-A, 1:333, Sigma-Aldrich, MO, USA).
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4997968&req=5

Figure 5: Longitudinal changes in MAO expression in the ACF model. Western blot was performed with samples from left ventricles of animals with ACF and sham-operated animals (animals sacrificed 8, 16, 24, and 51 weeks after creation of ACF). Each sample represents a pooled tissue homogenate from five animals from the individual group. Samples were loaded in duplicates on the 10% minigels. As a primary antibody rabbit anti-monoamine oxidase A was used (MAO-A, 1:333, Sigma-Aldrich, MO, USA).

Mentions: Since the role of adrenergic stimulation is well established in heart failure, we investigated separately the time course of adrenergic signaling in a parallel longitudinal study, using the catecholamine degradation enzyme monoamine oxidase (MAO) expression as a proxy (Figure 5). During the course of development of eccentric hypertrophy after creation of ACF, there was a steady increase in the adrenergic activity, evidenced by increased levels of MAO detected by Western blotting. These changes reached a plateau at 24 weeks, suggesting that near maximal adaptation was already in place during our sampling. Increased adrenergic stimulation can be viewed as an adaptive measure to increase myocardial performance during increased functional demands, despite blunting of the beta-adrenergic signaling reported in heart failure (Aiba and Tomaselli, 2010).


Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
Longitudinal changes in MAO expression in the ACF model. Western blot was performed with samples from left ventricles of animals with ACF and sham-operated animals (animals sacrificed 8, 16, 24, and 51 weeks after creation of ACF). Each sample represents a pooled tissue homogenate from five animals from the individual group. Samples were loaded in duplicates on the 10% minigels. As a primary antibody rabbit anti-monoamine oxidase A was used (MAO-A, 1:333, Sigma-Aldrich, MO, USA).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 5: Longitudinal changes in MAO expression in the ACF model. Western blot was performed with samples from left ventricles of animals with ACF and sham-operated animals (animals sacrificed 8, 16, 24, and 51 weeks after creation of ACF). Each sample represents a pooled tissue homogenate from five animals from the individual group. Samples were loaded in duplicates on the 10% minigels. As a primary antibody rabbit anti-monoamine oxidase A was used (MAO-A, 1:333, Sigma-Aldrich, MO, USA).
Mentions: Since the role of adrenergic stimulation is well established in heart failure, we investigated separately the time course of adrenergic signaling in a parallel longitudinal study, using the catecholamine degradation enzyme monoamine oxidase (MAO) expression as a proxy (Figure 5). During the course of development of eccentric hypertrophy after creation of ACF, there was a steady increase in the adrenergic activity, evidenced by increased levels of MAO detected by Western blotting. These changes reached a plateau at 24 weeks, suggesting that near maximal adaptation was already in place during our sampling. Increased adrenergic stimulation can be viewed as an adaptive measure to increase myocardial performance during increased functional demands, despite blunting of the beta-adrenergic signaling reported in heart failure (Aiba and Tomaselli, 2010).

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.