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Sympathetic β‐Adrenergic Stimulation Evokes Less Positive Inotropic Response But More Ventricular Arrhythmias in Heart Failure
Author(s) -
Greco Lisa V.,
Li Ying,
Zhang Youhua
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.02439
Subject(s) - dobutamine , medicine , inotrope , cardiology , heart failure , stimulation , ventricular fibrillation , ventricular tachycardia , adrenergic , hemodynamics , receptor
It is well‐known that heart failure (HF) results in impaired sympathetic autonomic signaling in the heart, known as “β‐adrenergic receptor downregulation or desensitization”. This results in reduced positive inotropic effect under β‐adrenergic stimulation in HF. Our recent data indicate that HF significantly alters sympathetic stimulation induced atrial fibrillation (AF) inducibility. In contrast to normal hearts, failing hears are more vulnerable to sympathetic stimulation induced AF. This study is to investigate whether ventricular arrhythmia inducibility is altered in HF by sympathetic β‐adrenergic stimulation. Methods HF was induced in 7 rats 2 months after myocardial infarction surgery with left coronary artery ligation, and 6 animals with sham surgery served as normal controls. Left ventricular pressure was recorded and the adrenergic β1‐agonist dobutamine (25μg/kg, iv) was administered to evoke positive inotropic effect. Ventricular arrhythmia inducibility test was performed with caffeine plus dobutamine challenge (caffeine 50mg/kg, ip, followed by dobutamine 25μg/kg, ip) and surface ECG as well as intracardiac right atrial electrocardiograms were recorded. Results Dobutamine induced positive inotropic effects were significantly less in HF rats than in sham‐controls (+dp/dt increased 49±13% in control versus 14±6% in HF, P<0.001). Caffeine and dobutamine challenge induced severe ventricular tachyarrhythmias (frequent premature ventricular contractions and ventricular tachycardia, figure) in 6/7 HF rats while no ventricular arrhythmia was induced in the controls (p<0.01). Conclusion Compared with normal hearts, failing hearts are much more vulnerable to develop severe ventricular tachyarrhythmia during sympathetic β‐adrenergic stimulation with dobutamine and caffeine challenge, despite β‐adrenergic receptor downregulation in HF, as reflected by the less positive inotropic effects induced by β‐adrenergic stimulation.Example of induced premature ventricular contractions (PVC) and ventricular tachycardia (VT)