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Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo.

Yaniv Y, Ahmet I, Tsutsui K, Behar J, Moen JM, Okamoto Y, Guiriba TR, Liu J, Bychkov R, Lakatta EG - Aging Cell (2016)

Bottom Line: BIV was quantified in both time and frequency domains using linear and nonlinear indices.In vivo basal BIV indices were found to be reduced with age, but this reduction diminished in the intrinsic state.But this compensation reduces the BIV due to both the imbalance of autonomic neural input to the pacemaker cells and altered pacemaker cell responses to neural input.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering Faculty, Technion-IIT, Haifa, Israel.

No MeSH data available.


Related in: MedlinePlus

Beating interval dynamics in response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in the isolated SAN ex vivo. Representative examples of (A) distribution of beating intervals, (B) regular and (C) normalized Poincaré plots of the beating intervals, and (D) power‐law behavior (log power spectrum density—PSD vs. log frequency) of beating interval response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in isolated SAN ex vivo. Percent of maximal changes in (E) beating rate, (F) coefficient of variance (CV), (G) fractal scaling exponent (β), and (H) approximate entropy in response to different degrees of PDE inhibition by IBMX in the SAN tissue isolated from adult (n = 6) and aged (n = 6) mice.
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acel12483-fig-0005: Beating interval dynamics in response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in the isolated SAN ex vivo. Representative examples of (A) distribution of beating intervals, (B) regular and (C) normalized Poincaré plots of the beating intervals, and (D) power‐law behavior (log power spectrum density—PSD vs. log frequency) of beating interval response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in isolated SAN ex vivo. Percent of maximal changes in (E) beating rate, (F) coefficient of variance (CV), (G) fractal scaling exponent (β), and (H) approximate entropy in response to different degrees of PDE inhibition by IBMX in the SAN tissue isolated from adult (n = 6) and aged (n = 6) mice.

Mentions: Reduced sensitivity to autonomic receptor agonists may, in part, be attributable to the mechanisms affecting the cAMP‐PKA signaling distal to surface membrane receptors. To test whether distal mechanisms to β‐AR lead to the reduced sensitivity, we employed a broad‐spectrum phosphodiesterase (PDE) inhibitor (IBMX) to increase the cAMP/PKA signaling in the isolated SAN tissue (Vinogradova et al., 2008; Liu et al., 2014). Representative examples and the average data of the average BI and BIV responses to PDE inhibition are shown in Fig. 5. Note that the responses to PDE inhibition mimic those to β‐AR stimulation: a reduction in average BI accompanied by a reduction in BIV, illustrated by BI histogram (Fig. 5A) and in the Poincaré plots (Fig. 5B–C), and quantified by linear indices (Table S8), fractal‐like complexity slope (Table S8, Fig. 5D), and system entropy (Table S8). Similar to the response to β‐AR stimulation, the sensitivity of BI and BIV to PDE inhibition was found to be reduced in advanced age compared to adults (Fig. 5E–H).


Deterioration of autonomic neuronal receptor signaling and mechanisms intrinsic to heart pacemaker cells contribute to age-associated alterations in heart rate variability in vivo.

Yaniv Y, Ahmet I, Tsutsui K, Behar J, Moen JM, Okamoto Y, Guiriba TR, Liu J, Bychkov R, Lakatta EG - Aging Cell (2016)

Beating interval dynamics in response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in the isolated SAN ex vivo. Representative examples of (A) distribution of beating intervals, (B) regular and (C) normalized Poincaré plots of the beating intervals, and (D) power‐law behavior (log power spectrum density—PSD vs. log frequency) of beating interval response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in isolated SAN ex vivo. Percent of maximal changes in (E) beating rate, (F) coefficient of variance (CV), (G) fractal scaling exponent (β), and (H) approximate entropy in response to different degrees of PDE inhibition by IBMX in the SAN tissue isolated from adult (n = 6) and aged (n = 6) mice.
© Copyright Policy - creativeCommonsBy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4933656&req=5

acel12483-fig-0005: Beating interval dynamics in response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in the isolated SAN ex vivo. Representative examples of (A) distribution of beating intervals, (B) regular and (C) normalized Poincaré plots of the beating intervals, and (D) power‐law behavior (log power spectrum density—PSD vs. log frequency) of beating interval response to PDE inhibition by 3′‐isobutylmethylxanthine (IBMX) in isolated SAN ex vivo. Percent of maximal changes in (E) beating rate, (F) coefficient of variance (CV), (G) fractal scaling exponent (β), and (H) approximate entropy in response to different degrees of PDE inhibition by IBMX in the SAN tissue isolated from adult (n = 6) and aged (n = 6) mice.
Mentions: Reduced sensitivity to autonomic receptor agonists may, in part, be attributable to the mechanisms affecting the cAMP‐PKA signaling distal to surface membrane receptors. To test whether distal mechanisms to β‐AR lead to the reduced sensitivity, we employed a broad‐spectrum phosphodiesterase (PDE) inhibitor (IBMX) to increase the cAMP/PKA signaling in the isolated SAN tissue (Vinogradova et al., 2008; Liu et al., 2014). Representative examples and the average data of the average BI and BIV responses to PDE inhibition are shown in Fig. 5. Note that the responses to PDE inhibition mimic those to β‐AR stimulation: a reduction in average BI accompanied by a reduction in BIV, illustrated by BI histogram (Fig. 5A) and in the Poincaré plots (Fig. 5B–C), and quantified by linear indices (Table S8), fractal‐like complexity slope (Table S8, Fig. 5D), and system entropy (Table S8). Similar to the response to β‐AR stimulation, the sensitivity of BI and BIV to PDE inhibition was found to be reduced in advanced age compared to adults (Fig. 5E–H).

Bottom Line: BIV was quantified in both time and frequency domains using linear and nonlinear indices.In vivo basal BIV indices were found to be reduced with age, but this reduction diminished in the intrinsic state.But this compensation reduces the BIV due to both the imbalance of autonomic neural input to the pacemaker cells and altered pacemaker cell responses to neural input.

View Article: PubMed Central - PubMed

Affiliation: Biomedical Engineering Faculty, Technion-IIT, Haifa, Israel.

No MeSH data available.


Related in: MedlinePlus