PMID- 34483832
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20220426
IS  - 1662-4548 (Print)
IS  - 1662-453X (Electronic)
IS  - 1662-453X (Linking)
VI  - 15
DP  - 2021
TI  - Reduced Cell Excitability of Cardiac Postganglionic Parasympathetic Neurons 
      Correlates With Myocardial Infarction-Induced Fatal Ventricular Arrhythmias in 
      Type 2 Diabetes Mellitus.
PG  - 721364
LID - 10.3389/fnins.2021.721364 [doi]
LID - 721364
AB  - OBJECTIVE: Withdrawal of cardiac vagal activity is considered as one of the 
      important triggers for acute myocardial infarction (MI)-induced ventricular 
      arrhythmias in type 2 diabetes mellitus (T2DM). Our previous study demonstrated 
      that cell excitability of cardiac parasympathetic postganglionic (CPP) neurons 
      was reduced in T2DM rats. This study investigated whether cell excitability of 
      CPP neurons is associated with cardiac vagal activity and MI-induced ventricular 
      arrhythmias in T2DM rats. METHODS: Rat T2DM was induced by a high-fat diet plus 
      streptozotocin injection. MI-evoked ventricular arrhythmia was achieved by 
      surgical ligation of the left anterior descending coronary artery. 
      Twenty-four-hour, continuous ECG recording was used to quantify ventricular 
      arrhythmic events and heart rate variability (HRV) in conscious rats. The power 
      spectral analysis of HRV was used to evaluate autonomic function. Cell 
      excitability of CPP neurons was measured by the whole-cell patch-clamp technique. 
      RESULTS: Twenty-four-hour ECG data demonstrated that MI-evoked fatal ventricular 
      arrhythmias are more severe in T2DM rats than that in sham rats. In addition, the 
      Kaplan-Meier analysis demonstrated that the survival rate over 2 weeks after MI 
      is significantly lower in T2DM rats (15% in T2DM+MI) compared to sham rats (75% 
      in sham+MI). The susceptibility to ventricular tachyarrhythmia elicited by 
      programmed electrical stimulation was higher in anesthetized T2DM+MI rats than 
      that in rats with MI or T2DM alone (7.0 +/- 0.58 in T2DM+MI group vs. 3.5 +/- 0.76 in 
      sham+MI). Moreover, as an index for vagal control of ventricular function, 
      changes of left ventricular systolic pressure (LVSP) and the maximum rate of 
      increase of left ventricular pressure (LV dP/dt(max)) in response to vagal 
      efferent nerve stimulation were blunted in T2DM rats. Furthermore, T2DM increased 
      heterogeneity of ventricular electrical activities and reduced cardiac 
      parasympathetic activity and cell excitability of CPP neurons (current 
      threshold-inducing action potentials being 62 +/- 3.3 pA in T2DM rats without MI 
      vs. 27 +/- 1.9 pA in sham rats without MI). However, MI did not alter vagal control 
      of the ventricular function and CPP neuronal excitability, although it also 
      induced cardiac autonomic dysfunction and enhanced heterogeneity of ventricular 
      electrical activities. CONCLUSION: The reduction of CPP neuron excitability is 
      involved in decreased cardiac vagal function, including cardiac parasympathetic 
      activity and vagal control of ventricular function, which is associated with 
      MI-induced high mortality and malignant ventricular arrhythmias in T2DM.
CI  - Copyright (c) 2021 Hu, Zhang, Tu and Li.
FAU - Hu, Wenfeng
AU  - Hu W
AD  - Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, 
      NE, United States.
FAU - Zhang, Dongze
AU  - Zhang D
AD  - Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, 
      NE, United States.
FAU - Tu, Huiyin
AU  - Tu H
AD  - Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, 
      NE, United States.
FAU - Li, Yu-Long
AU  - Li YL
AD  - Department of Emergency Medicine, University of Nebraska Medical Center, Omaha, 
      NE, United States.
AD  - Department of Cellular & Integrative Physiology, University of Nebraska Medical 
      Center, Omaha, NE, United States.
LA  - eng
GR  - R01 HL137832/HL/NHLBI NIH HHS/United States
GR  - R01 HL144146/HL/NHLBI NIH HHS/United States
PT  - Journal Article
DEP - 20210818
PL  - Switzerland
TA  - Front Neurosci
JT  - Frontiers in neuroscience
JID - 101478481
PMC - PMC8416412
OTO - NOTNLM
OT  - action potential
OT  - cardiac autonomic neuropathy
OT  - cardiac vagal neuron
OT  - diabetes mellitus
OT  - heart rate variability
OT  - myocardial infarction
OT  - ventricular arrhythmias
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2021/09/07 06:00
MHDA- 2021/09/07 06:01
PMCR- 2021/01/01
CRDT- 2021/09/06 05:53
PHST- 2021/06/06 00:00 [received]
PHST- 2021/07/30 00:00 [accepted]
PHST- 2021/09/06 05:53 [entrez]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2021/09/07 06:01 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - 10.3389/fnins.2021.721364 [doi]
PST - epublish
SO  - Front Neurosci. 2021 Aug 18;15:721364. doi: 10.3389/fnins.2021.721364. 
      eCollection 2021.