Reducing the Cyclic Variations of Ultrasonic Integrated Backscatters and Myocardial Electrical Synchronism by Reversibly Blocking Intercellular Communications with Heptanol

Lung Chun Lin, Chau Chung Wu, Mao Shin Lin, Shien Fong Lin, Yen Bin Liu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

The purpose of this study is to provide direct evidence for the role of intercellular communications in electrical synchronization and mechanical function of myocardium. We used heptanol, a reversible inhibitor of gap junctions, at low (0.16 mM) and high (0.5 mM) concentration as perfusate for 18 Langendorff-perfused rabbit hearts to study its effects on myocardial electrical and mechanical functions. Optical mapping was performed to measure conduction velocity (CV) and action potential duration (APD). Ultrasonic integrated backscatter and Doppler tissue imaging (DTI) were used to evaluate the intrinsic and global myocardial contractile performance. The CV decreased during low-dose heptanol infusion and became much slower at high dose (high dose vs. baseline, 50.8 ± 10.2 cm/s vs. 69.3 ± 8.8 cm/s, p < 0.001). After washout of heptanol, CV completely recovered. The alterations of APD by heptanol infusion were similar to CV. The APD dispersion, standard deviation of APD80, was increased after heptanol infusion (low dose vs. baseline, 5.9 ± 1.1 ms vs. 4.3 ± 1.1 ms, p = 0.004; high dose, 6.0 ± 1.3 ms, vs. baseline, p = 0.035). However, washout did not restore the APD dispersion which became even larger after washout (13.6 ± 1.9 ms vs. high dose and baseline, both p < 0.001). Regarding contractile function, heptanol treatment resulted in a progressive decrease of cardiac cycle-dependent variations of integrated backscatter (CVIBS; low dose vs. baseline, 6.1 ± 1.7 dB vs. 7.2 ± 1.8 dB, p = 0.007; high dose 1.7 ± 0.3 dB vs. baseline, p < 0.001) and peak systolic strain rate (low dose vs. baseline, -1.5 ± 0.6 1/s vs. -1.9 ± 0.6 1/s, p = 0.014; high dose -0.4 ± 0.2 1/s; vs. baseline, p < 0.001). That both CVIBS and strain rate incompletely recovered after heptanol washout may be attributed to the increased APD dispersion. In conclusion, uncoupling of gap junctions resulted in slowing CV, increased repolarization heterogeneity, reduced CVIBS and impaired myocardial contractility. There was a reversible dose-response relationship between the myocardial electromechanical functions and gap junction coupling. (E-mail: yenbin@ntu.edu.tw).

Original languageEnglish (US)
Pages (from-to)209-218
Number of pages10
JournalUltrasound in Medicine and Biology
Volume35
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Heptanol
Ultrasonics
synchronism
ultrasonics
communication
Action Potentials
dosage
Gap Junctions
fallout
conduction
strain rate
Myocardium
myocardium
rabbits
Rabbits
inhibitors
standard deviation

Keywords

  • Connexin
  • Heptanol
  • Optical mapping
  • Strain rate imaging
  • Ultrasonic integrated backscatters

ASJC Scopus subject areas

  • Radiology Nuclear Medicine and imaging
  • Radiological and Ultrasound Technology
  • Biophysics

Cite this

Reducing the Cyclic Variations of Ultrasonic Integrated Backscatters and Myocardial Electrical Synchronism by Reversibly Blocking Intercellular Communications with Heptanol. / Lin, Lung Chun; Wu, Chau Chung; Lin, Mao Shin; Lin, Shien Fong; Liu, Yen Bin.

In: Ultrasound in Medicine and Biology, Vol. 35, No. 2, 01.02.2009, p. 209-218.

Research output: Contribution to journalArticle

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AU - Lin, Shien Fong

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N2 - The purpose of this study is to provide direct evidence for the role of intercellular communications in electrical synchronization and mechanical function of myocardium. We used heptanol, a reversible inhibitor of gap junctions, at low (0.16 mM) and high (0.5 mM) concentration as perfusate for 18 Langendorff-perfused rabbit hearts to study its effects on myocardial electrical and mechanical functions. Optical mapping was performed to measure conduction velocity (CV) and action potential duration (APD). Ultrasonic integrated backscatter and Doppler tissue imaging (DTI) were used to evaluate the intrinsic and global myocardial contractile performance. The CV decreased during low-dose heptanol infusion and became much slower at high dose (high dose vs. baseline, 50.8 ± 10.2 cm/s vs. 69.3 ± 8.8 cm/s, p < 0.001). After washout of heptanol, CV completely recovered. The alterations of APD by heptanol infusion were similar to CV. The APD dispersion, standard deviation of APD80, was increased after heptanol infusion (low dose vs. baseline, 5.9 ± 1.1 ms vs. 4.3 ± 1.1 ms, p = 0.004; high dose, 6.0 ± 1.3 ms, vs. baseline, p = 0.035). However, washout did not restore the APD dispersion which became even larger after washout (13.6 ± 1.9 ms vs. high dose and baseline, both p < 0.001). Regarding contractile function, heptanol treatment resulted in a progressive decrease of cardiac cycle-dependent variations of integrated backscatter (CVIBS; low dose vs. baseline, 6.1 ± 1.7 dB vs. 7.2 ± 1.8 dB, p = 0.007; high dose 1.7 ± 0.3 dB vs. baseline, p < 0.001) and peak systolic strain rate (low dose vs. baseline, -1.5 ± 0.6 1/s vs. -1.9 ± 0.6 1/s, p = 0.014; high dose -0.4 ± 0.2 1/s; vs. baseline, p < 0.001). That both CVIBS and strain rate incompletely recovered after heptanol washout may be attributed to the increased APD dispersion. In conclusion, uncoupling of gap junctions resulted in slowing CV, increased repolarization heterogeneity, reduced CVIBS and impaired myocardial contractility. There was a reversible dose-response relationship between the myocardial electromechanical functions and gap junction coupling. (E-mail: yenbin@ntu.edu.tw).

AB - The purpose of this study is to provide direct evidence for the role of intercellular communications in electrical synchronization and mechanical function of myocardium. We used heptanol, a reversible inhibitor of gap junctions, at low (0.16 mM) and high (0.5 mM) concentration as perfusate for 18 Langendorff-perfused rabbit hearts to study its effects on myocardial electrical and mechanical functions. Optical mapping was performed to measure conduction velocity (CV) and action potential duration (APD). Ultrasonic integrated backscatter and Doppler tissue imaging (DTI) were used to evaluate the intrinsic and global myocardial contractile performance. The CV decreased during low-dose heptanol infusion and became much slower at high dose (high dose vs. baseline, 50.8 ± 10.2 cm/s vs. 69.3 ± 8.8 cm/s, p < 0.001). After washout of heptanol, CV completely recovered. The alterations of APD by heptanol infusion were similar to CV. The APD dispersion, standard deviation of APD80, was increased after heptanol infusion (low dose vs. baseline, 5.9 ± 1.1 ms vs. 4.3 ± 1.1 ms, p = 0.004; high dose, 6.0 ± 1.3 ms, vs. baseline, p = 0.035). However, washout did not restore the APD dispersion which became even larger after washout (13.6 ± 1.9 ms vs. high dose and baseline, both p < 0.001). Regarding contractile function, heptanol treatment resulted in a progressive decrease of cardiac cycle-dependent variations of integrated backscatter (CVIBS; low dose vs. baseline, 6.1 ± 1.7 dB vs. 7.2 ± 1.8 dB, p = 0.007; high dose 1.7 ± 0.3 dB vs. baseline, p < 0.001) and peak systolic strain rate (low dose vs. baseline, -1.5 ± 0.6 1/s vs. -1.9 ± 0.6 1/s, p = 0.014; high dose -0.4 ± 0.2 1/s; vs. baseline, p < 0.001). That both CVIBS and strain rate incompletely recovered after heptanol washout may be attributed to the increased APD dispersion. In conclusion, uncoupling of gap junctions resulted in slowing CV, increased repolarization heterogeneity, reduced CVIBS and impaired myocardial contractility. There was a reversible dose-response relationship between the myocardial electromechanical functions and gap junction coupling. (E-mail: yenbin@ntu.edu.tw).

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