Cariporide (HOE642) attenuates lactic acidosis induced pulmonary vein arrhythmogenesis

Ameya R. Udyavar, Yao Chang Chen, Chen Chuan Cheng, Satoshi Higa, Yi J. Chen, Shih A. Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Aims: Lactic acidosis causes atrial fibrillation (AF), and pulmonary veins (PVs) are the most important focus for the generation of AF. Cariporide (HOE642), a Na+/H+ blocker, can prevent atrial tachycardia-induced electrical remodeling. The purpose of this study was to investigate whether cariporide can prevent lactic acidosis-induced PV arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs) before and after the administration of lactic acid (10 and 20 mM) in the absence and presence of cariporide (10 μM) pretreatment in isolated rabbit PV and atrial tissue preparations. Key findings: Lactic acidosis of 10 mM (pH 7.0 ± 0.1) and 20 mM (pH 6.7 ± 0.1) reduced PV (n = 6) spontaneous rates from 2.5 ± 0.3 to 1.6 ± 0.4 (by 36 ± 1%) and 1.1 ± 0.4 Hz (by 56 ± 2%), respectively, but lactic acidosis (10 and 20 mM) induced 12 episodes (3.9 ± 0.2 Hz) and 23 episodes (4.0 ± 0.3 Hz) of non-sustained burst firings in 4 PV specimens. Lactic acidosis (10 and 20 mM) decreased the AP amplitude (APA) and velocity of depolarization (Vmax), but increased the resting membrane potential (RMP), AP duration, and strength-response interval (SRI) in the PV and atrium. In the presence of cariporide (10 μM), lactic acidosis (10 and 20 mM) only reduced PV spontaneous rates from 2.4 ± 0.2 to 1.8 ± 0.4 (by 25 ± 1%) and 1.6 ± 0.4 Hz (by 33 ± 1%), respectively, and prevented lactic acidosis-induced PV burst firings. Cariporide also reduced the effects of lactic acidosis on the RMP, AP duration, APA, Vmax, and SRI. Significance: Lactic acidosis has significant arrhythmogenic effects on PVs, which may be attenuated by Na+/H+ blockers.

Original languageEnglish
Pages (from-to)19-25
Number of pages7
JournalLife Sciences
Volume85
Issue number1-2
DOIs
Publication statusPublished - Jul 1 2009

Fingerprint

Lactic Acidosis
Pulmonary Veins
Action Potentials
Membrane Potentials
Atrial Fibrillation
Atrial Remodeling
Membranes
cariporide
Milk
Microelectrodes
Depolarization
Tachycardia
Lactic Acid
Tissue
Rabbits

Keywords

  • Cariporide
  • Lactic acidosis
  • Pulmonary veins

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

Cariporide (HOE642) attenuates lactic acidosis induced pulmonary vein arrhythmogenesis. / Udyavar, Ameya R.; Chen, Yao Chang; Cheng, Chen Chuan; Higa, Satoshi; Chen, Yi J.; Chen, Shih A.

In: Life Sciences, Vol. 85, No. 1-2, 01.07.2009, p. 19-25.

Research output: Contribution to journalArticle

Udyavar, Ameya R. ; Chen, Yao Chang ; Cheng, Chen Chuan ; Higa, Satoshi ; Chen, Yi J. ; Chen, Shih A. / Cariporide (HOE642) attenuates lactic acidosis induced pulmonary vein arrhythmogenesis. In: Life Sciences. 2009 ; Vol. 85, No. 1-2. pp. 19-25.
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abstract = "Aims: Lactic acidosis causes atrial fibrillation (AF), and pulmonary veins (PVs) are the most important focus for the generation of AF. Cariporide (HOE642), a Na+/H+ blocker, can prevent atrial tachycardia-induced electrical remodeling. The purpose of this study was to investigate whether cariporide can prevent lactic acidosis-induced PV arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs) before and after the administration of lactic acid (10 and 20 mM) in the absence and presence of cariporide (10 μM) pretreatment in isolated rabbit PV and atrial tissue preparations. Key findings: Lactic acidosis of 10 mM (pH 7.0 ± 0.1) and 20 mM (pH 6.7 ± 0.1) reduced PV (n = 6) spontaneous rates from 2.5 ± 0.3 to 1.6 ± 0.4 (by 36 ± 1{\%}) and 1.1 ± 0.4 Hz (by 56 ± 2{\%}), respectively, but lactic acidosis (10 and 20 mM) induced 12 episodes (3.9 ± 0.2 Hz) and 23 episodes (4.0 ± 0.3 Hz) of non-sustained burst firings in 4 PV specimens. Lactic acidosis (10 and 20 mM) decreased the AP amplitude (APA) and velocity of depolarization (Vmax), but increased the resting membrane potential (RMP), AP duration, and strength-response interval (SRI) in the PV and atrium. In the presence of cariporide (10 μM), lactic acidosis (10 and 20 mM) only reduced PV spontaneous rates from 2.4 ± 0.2 to 1.8 ± 0.4 (by 25 ± 1{\%}) and 1.6 ± 0.4 Hz (by 33 ± 1{\%}), respectively, and prevented lactic acidosis-induced PV burst firings. Cariporide also reduced the effects of lactic acidosis on the RMP, AP duration, APA, Vmax, and SRI. Significance: Lactic acidosis has significant arrhythmogenic effects on PVs, which may be attenuated by Na+/H+ blockers.",
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AU - Chen, Yao Chang

AU - Cheng, Chen Chuan

AU - Higa, Satoshi

AU - Chen, Yi J.

AU - Chen, Shih A.

PY - 2009/7/1

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N2 - Aims: Lactic acidosis causes atrial fibrillation (AF), and pulmonary veins (PVs) are the most important focus for the generation of AF. Cariporide (HOE642), a Na+/H+ blocker, can prevent atrial tachycardia-induced electrical remodeling. The purpose of this study was to investigate whether cariporide can prevent lactic acidosis-induced PV arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs) before and after the administration of lactic acid (10 and 20 mM) in the absence and presence of cariporide (10 μM) pretreatment in isolated rabbit PV and atrial tissue preparations. Key findings: Lactic acidosis of 10 mM (pH 7.0 ± 0.1) and 20 mM (pH 6.7 ± 0.1) reduced PV (n = 6) spontaneous rates from 2.5 ± 0.3 to 1.6 ± 0.4 (by 36 ± 1%) and 1.1 ± 0.4 Hz (by 56 ± 2%), respectively, but lactic acidosis (10 and 20 mM) induced 12 episodes (3.9 ± 0.2 Hz) and 23 episodes (4.0 ± 0.3 Hz) of non-sustained burst firings in 4 PV specimens. Lactic acidosis (10 and 20 mM) decreased the AP amplitude (APA) and velocity of depolarization (Vmax), but increased the resting membrane potential (RMP), AP duration, and strength-response interval (SRI) in the PV and atrium. In the presence of cariporide (10 μM), lactic acidosis (10 and 20 mM) only reduced PV spontaneous rates from 2.4 ± 0.2 to 1.8 ± 0.4 (by 25 ± 1%) and 1.6 ± 0.4 Hz (by 33 ± 1%), respectively, and prevented lactic acidosis-induced PV burst firings. Cariporide also reduced the effects of lactic acidosis on the RMP, AP duration, APA, Vmax, and SRI. Significance: Lactic acidosis has significant arrhythmogenic effects on PVs, which may be attenuated by Na+/H+ blockers.

AB - Aims: Lactic acidosis causes atrial fibrillation (AF), and pulmonary veins (PVs) are the most important focus for the generation of AF. Cariporide (HOE642), a Na+/H+ blocker, can prevent atrial tachycardia-induced electrical remodeling. The purpose of this study was to investigate whether cariporide can prevent lactic acidosis-induced PV arrhythmogenesis. Main methods: Conventional microelectrodes were used to record the action potentials (APs) before and after the administration of lactic acid (10 and 20 mM) in the absence and presence of cariporide (10 μM) pretreatment in isolated rabbit PV and atrial tissue preparations. Key findings: Lactic acidosis of 10 mM (pH 7.0 ± 0.1) and 20 mM (pH 6.7 ± 0.1) reduced PV (n = 6) spontaneous rates from 2.5 ± 0.3 to 1.6 ± 0.4 (by 36 ± 1%) and 1.1 ± 0.4 Hz (by 56 ± 2%), respectively, but lactic acidosis (10 and 20 mM) induced 12 episodes (3.9 ± 0.2 Hz) and 23 episodes (4.0 ± 0.3 Hz) of non-sustained burst firings in 4 PV specimens. Lactic acidosis (10 and 20 mM) decreased the AP amplitude (APA) and velocity of depolarization (Vmax), but increased the resting membrane potential (RMP), AP duration, and strength-response interval (SRI) in the PV and atrium. In the presence of cariporide (10 μM), lactic acidosis (10 and 20 mM) only reduced PV spontaneous rates from 2.4 ± 0.2 to 1.8 ± 0.4 (by 25 ± 1%) and 1.6 ± 0.4 Hz (by 33 ± 1%), respectively, and prevented lactic acidosis-induced PV burst firings. Cariporide also reduced the effects of lactic acidosis on the RMP, AP duration, APA, Vmax, and SRI. Significance: Lactic acidosis has significant arrhythmogenic effects on PVs, which may be attenuated by Na+/H+ blockers.

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