Acute restraint stress provokes sudden cardiac death in normotensive rats and enhances susceptibility to arrhythmogenic effects of adrenaline in spontaneously hypertensive rats

• The mechanisms of acute-restraint-stress-induced sudden cardiac death are disclosed.
• Sympathetic activity and gap junction are related to sudden cardiac death.
• The diagnostic markers for sudden cardiac death are proposed.

BackgroundA high incidence of cardiovascular events and sudden cardiac death (SCD) has been reported following unexpected acute psychosocial stress. The possible pathways by which acute restraint stress (ARS), a kind of acute psychosocial stress, leads to SCD were determined.MethodsUsing 16-week-old male normotensive Wistar Kyoto rats (WKY, n = 24) as controls and spontaneously hypertensive rats (SHR, n = 24) as the hypertensive subjects with left ventricular hypertrophy (LVH), we assessed ARS-related incidence of SCD, cardiac and myocardial autonomic nervous system dysfunction, gap junction connexin-43 (Cx43) channel remodeling, and ventricular repolarization abnormality, based on electrocardiography, an adrenaline test, heart rate variability (HRV), and reverse transcriptase polymerase chain reaction analyses. Rats with ARS were introduced into restrainers that allowed head, limb, and tail movement.ResultsIn normotensive hearts without LVH, ARS induced a higher incidence of SCD attributed to lethal bradycardia, increased cardiac and myocardial sympathetic activation, and gap junction Cx43 channel remodeling, as evidenced by the increases in the ratio of low-frequency and high-frequency powers in HRV, the ratio of myocardial neuropeptide Y (NPY) and acetylcholinesterase (AChE) mRNA expressions, and the up-regulation of LV Cx43 mRNA expression; in hypertensive hearts with LVH, ARS enhanced susceptibility to the malignant arrhythmogenic effects of the adrenaline test (a kind of sympathetic stimuli) accompanied by abnormal ventricular repolarization, as evidenced by increased incidence of ventricular tachycardia and/or ventricular fibrillation during the adrenaline test and prolonged QTc immediately after ARS.ConclusionsARS may trigger cardiac and myocardial sympathetic predominance, and then induce gap junction Cx43 channel remodeling, finally leading to lethal bradycardia in normotensive WKY. ARS-induced abnormal ventricular repolarization may be responsible for ARS-enhanced susceptibility to sympathetic stimulation in SHR with LVH. Expressions of myocardial NPY, AChE, and Cx43 genes, HRV, QTc and LVH measures showed diagnostic and prognostic potential for predicting ARS-induced SCD.

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