Antioxidant defense and protection against cardiac arrhythmias: Lessons from a mammalian hibernator (the woodchuck)

Zhenghang Zhao, Raymond K. Kudej, Hairuo Wen, Nadezhda Fefelova, Lin Yan, Dorothy Vatner, Stephen Vatner, Lai-Hua Xie

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Hibernating animals show resistance to hypothermia-induced cardiac arrhythmias. However, it is not clear whether and how mammalian hibernators are resistant to ischemia-induced arrhythmias. The goal of this investigation was to determine the susceptibility of woodchucks (Marmota monax) to arrhythmias and their mechanisms after coronary artery occlusion at the same room temperature in both winter, the time for hibernation, and summer, when they do not hibernate. By monitoring telemetric electrocardiograms, we found significantly higher arrhythmia scores, calculated as the severity of arrhythmias, with incidence of ventricular tachycardia, ventricular fibrillation, and thus sudden cardiac death (SCD) in woodchucks in summer than they had in winter. The level of catalase expression in woodchuck hearts was significantly higher, whereas the level of oxidized Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) was lower in winter than it was in summer. Ventricular myocytes isolated from woodchucks in winter were more resistant to H 2 O 2 -induced early afterdepolarizations (EADs) compared with myocytes isolated from woodchucks in summer. The EADs were eliminated by inhibiting CaMKII (with KN-93), L-type Ca current (with nifedipine), or late Na + current (with ranolazine). In woodchucks, in the summer, the arrhythmia score was significantly reduced by overexpression of catalase (via adenoviral vectors) or the inhibition of CaMKII (with KN-93) in the heart. This study suggests that the heart of the mammalian hibernator is more resistant to ischemia-induced arrhythmias and SCD in winter. Increased antioxidative capacity and reduced CaMKII activity may confer resistance in woodchuck hearts against EADs and arrhythmias during winter. The profound protection conferred by catalase overexpression or CaMKII inhibition in this novel natural animal model may provide insights into clinical directions for therapy of arrhythmias.

Original languageEnglish (US)
Pages (from-to)4229-4240
Number of pages12
JournalFASEB Journal
Volume32
Issue number8
DOIs
StatePublished - Aug 1 2018

Fingerprint

Marmota
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Cardiac Arrhythmias
Antioxidants
Catalase
Animals
Hypothermia
Sudden Cardiac Death
Calcium-Calmodulin-Dependent Protein Kinases
Nifedipine
Muscle Cells
Electrocardiography
Ischemia
Induced Hypothermia
Hibernation
Coronary Occlusion
Ventricular Fibrillation
Ventricular Tachycardia
Monitoring
Coronary Vessels

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Keywords

  • CaMKII
  • Hibernating animals
  • Ischemia
  • Oxidative stress
  • Triggered activity

Cite this

Zhao, Zhenghang ; Kudej, Raymond K. ; Wen, Hairuo ; Fefelova, Nadezhda ; Yan, Lin ; Vatner, Dorothy ; Vatner, Stephen ; Xie, Lai-Hua. / Antioxidant defense and protection against cardiac arrhythmias : Lessons from a mammalian hibernator (the woodchuck). In: FASEB Journal. 2018 ; Vol. 32, No. 8. pp. 4229-4240.
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Antioxidant defense and protection against cardiac arrhythmias : Lessons from a mammalian hibernator (the woodchuck). / Zhao, Zhenghang; Kudej, Raymond K.; Wen, Hairuo; Fefelova, Nadezhda; Yan, Lin; Vatner, Dorothy; Vatner, Stephen; Xie, Lai-Hua.

In: FASEB Journal, Vol. 32, No. 8, 01.08.2018, p. 4229-4240.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Antioxidant defense and protection against cardiac arrhythmias

T2 - Lessons from a mammalian hibernator (the woodchuck)

AU - Zhao, Zhenghang

AU - Kudej, Raymond K.

AU - Wen, Hairuo

AU - Fefelova, Nadezhda

AU - Yan, Lin

AU - Vatner, Dorothy

AU - Vatner, Stephen

AU - Xie, Lai-Hua

PY - 2018/8/1

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N2 - Hibernating animals show resistance to hypothermia-induced cardiac arrhythmias. However, it is not clear whether and how mammalian hibernators are resistant to ischemia-induced arrhythmias. The goal of this investigation was to determine the susceptibility of woodchucks (Marmota monax) to arrhythmias and their mechanisms after coronary artery occlusion at the same room temperature in both winter, the time for hibernation, and summer, when they do not hibernate. By monitoring telemetric electrocardiograms, we found significantly higher arrhythmia scores, calculated as the severity of arrhythmias, with incidence of ventricular tachycardia, ventricular fibrillation, and thus sudden cardiac death (SCD) in woodchucks in summer than they had in winter. The level of catalase expression in woodchuck hearts was significantly higher, whereas the level of oxidized Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) was lower in winter than it was in summer. Ventricular myocytes isolated from woodchucks in winter were more resistant to H 2 O 2 -induced early afterdepolarizations (EADs) compared with myocytes isolated from woodchucks in summer. The EADs were eliminated by inhibiting CaMKII (with KN-93), L-type Ca current (with nifedipine), or late Na + current (with ranolazine). In woodchucks, in the summer, the arrhythmia score was significantly reduced by overexpression of catalase (via adenoviral vectors) or the inhibition of CaMKII (with KN-93) in the heart. This study suggests that the heart of the mammalian hibernator is more resistant to ischemia-induced arrhythmias and SCD in winter. Increased antioxidative capacity and reduced CaMKII activity may confer resistance in woodchuck hearts against EADs and arrhythmias during winter. The profound protection conferred by catalase overexpression or CaMKII inhibition in this novel natural animal model may provide insights into clinical directions for therapy of arrhythmias.

AB - Hibernating animals show resistance to hypothermia-induced cardiac arrhythmias. However, it is not clear whether and how mammalian hibernators are resistant to ischemia-induced arrhythmias. The goal of this investigation was to determine the susceptibility of woodchucks (Marmota monax) to arrhythmias and their mechanisms after coronary artery occlusion at the same room temperature in both winter, the time for hibernation, and summer, when they do not hibernate. By monitoring telemetric electrocardiograms, we found significantly higher arrhythmia scores, calculated as the severity of arrhythmias, with incidence of ventricular tachycardia, ventricular fibrillation, and thus sudden cardiac death (SCD) in woodchucks in summer than they had in winter. The level of catalase expression in woodchuck hearts was significantly higher, whereas the level of oxidized Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) was lower in winter than it was in summer. Ventricular myocytes isolated from woodchucks in winter were more resistant to H 2 O 2 -induced early afterdepolarizations (EADs) compared with myocytes isolated from woodchucks in summer. The EADs were eliminated by inhibiting CaMKII (with KN-93), L-type Ca current (with nifedipine), or late Na + current (with ranolazine). In woodchucks, in the summer, the arrhythmia score was significantly reduced by overexpression of catalase (via adenoviral vectors) or the inhibition of CaMKII (with KN-93) in the heart. This study suggests that the heart of the mammalian hibernator is more resistant to ischemia-induced arrhythmias and SCD in winter. Increased antioxidative capacity and reduced CaMKII activity may confer resistance in woodchuck hearts against EADs and arrhythmias during winter. The profound protection conferred by catalase overexpression or CaMKII inhibition in this novel natural animal model may provide insights into clinical directions for therapy of arrhythmias.

KW - CaMKII

KW - Hibernating animals

KW - Ischemia

KW - Oxidative stress

KW - Triggered activity

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