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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.


Representative ECG and EP recordings highlighting the changes in quantitative parameters. Note an increased P wave amplitude and duration, increased R amplitude, and prolonged QRS duration in a typical ACF recording. Prolongation of APD50 (right column) is present in the ACF group as whole (compare with the sub-group values in Table 1).
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Figure 1: Representative ECG and EP recordings highlighting the changes in quantitative parameters. Note an increased P wave amplitude and duration, increased R amplitude, and prolonged QRS duration in a typical ACF recording. Prolongation of APD50 (right column) is present in the ACF group as whole (compare with the sub-group values in Table 1).

Mentions: Rats were anesthetized with an intraperitoneal injection of ketamine/midazolam (50/5 mg/kg). Four ECG leads were attached at the proximal part of the limbs using clips attached to subcutaneous needles. ECG recording was performed using FE 132 Bioamp and Powerlab 8 (ADInstruments, Australia) data acquisition tool with 1 kHz sampling. Recordings were off-line analyzed using LabChart Pro 7 program with ECG module, with built-in algorithm for wave detection specific to rodents. Successive 200 beats were extracted from the LabChart channel from the lead with the best signal to noise ratio (lead aVR). The beats labeled as good by the classifier were averaged using alignment to the QRS maximum to form a single beat for analysis (Figure 1). The R wave was identified by the program as the most positive value in the neighborhood of the Beat Marker. The start and end of the QRS complex were determined by searches on each side of the R wave for regions where the slope (dV/dt) falls to sufficiently low values. Isoelectric level was defined as the median of all data values preceding the QRS complex. Absolute values of Q, R, and S were added to calculated QRS sum voltage. The peak of the P wave was defined as the point of the greatest absolute deviation from the isoelectric line in the interval from pre-P to just before the beginning of QRS. The beginning of P wave was determined by intersection of the isoelectric line and a straight line fitted by least squares to points 15–60% prior of the peak of P wave. T wave was defined as the first significant peak of either sign, starting from the point after the end of QRS. The end of T was defined by the first return to isoelectric level. ST height was arbitrarily measured 15 ms after QRS alignment point. QT interval was corrected for heart rate (QTc) using the Bazett formula.


Changes in Myocardial Composition and Conduction Properties in Rat Heart Failure Model Induced by Chronic Volume Overload
Representative ECG and EP recordings highlighting the changes in quantitative parameters. Note an increased P wave amplitude and duration, increased R amplitude, and prolonged QRS duration in a typical ACF recording. Prolongation of APD50 (right column) is present in the ACF group as whole (compare with the sub-group values in Table 1).
© Copyright Policy
Related In: Results  -  Collection

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

Figure 1: Representative ECG and EP recordings highlighting the changes in quantitative parameters. Note an increased P wave amplitude and duration, increased R amplitude, and prolonged QRS duration in a typical ACF recording. Prolongation of APD50 (right column) is present in the ACF group as whole (compare with the sub-group values in Table 1).
Mentions: Rats were anesthetized with an intraperitoneal injection of ketamine/midazolam (50/5 mg/kg). Four ECG leads were attached at the proximal part of the limbs using clips attached to subcutaneous needles. ECG recording was performed using FE 132 Bioamp and Powerlab 8 (ADInstruments, Australia) data acquisition tool with 1 kHz sampling. Recordings were off-line analyzed using LabChart Pro 7 program with ECG module, with built-in algorithm for wave detection specific to rodents. Successive 200 beats were extracted from the LabChart channel from the lead with the best signal to noise ratio (lead aVR). The beats labeled as good by the classifier were averaged using alignment to the QRS maximum to form a single beat for analysis (Figure 1). The R wave was identified by the program as the most positive value in the neighborhood of the Beat Marker. The start and end of the QRS complex were determined by searches on each side of the R wave for regions where the slope (dV/dt) falls to sufficiently low values. Isoelectric level was defined as the median of all data values preceding the QRS complex. Absolute values of Q, R, and S were added to calculated QRS sum voltage. The peak of the P wave was defined as the point of the greatest absolute deviation from the isoelectric line in the interval from pre-P to just before the beginning of QRS. The beginning of P wave was determined by intersection of the isoelectric line and a straight line fitted by least squares to points 15–60% prior of the peak of P wave. T wave was defined as the first significant peak of either sign, starting from the point after the end of QRS. The end of T was defined by the first return to isoelectric level. ST height was arbitrarily measured 15 ms after QRS alignment point. QT interval was corrected for heart rate (QTc) using the Bazett formula.

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.