Central beta-adrenergic mechanisms may modulate ischemic ventricular fibrillation in pigs.

Abstract

A central noradrenergic process may permit expression of the stress-related increase in cardiac vulnerability to ventricular fibrillation (VF). Thus, the effect of central j8-adrenergic receptor blockade with L-propranolol (0.01 The high dose of L-propranolol also reduced the incidence of VF (7/15 fibrillated) compared with Ringer's solution (12/12 fibrillated) and D-propranolol (6/7 fibrillated). The lower dose of L-propranolol was without effect on VF vulnerability (7/9 fibrillated). The plasma concentration resulting from central administration of 0.05 mg/kg L-propranolol was found to be 9.05+±3.25 ng/ml, which is significantly below therapeutic antiarrhythmic blood levels. We conclude that the reduced vulnerability to ischemia-induced VF after intracerebroventricular administration of propranolol is due to alteration of a central P-adrenergic receptor-mediated phenomenon as opposed to an effect on the heart directly or to nonspecific membrane stabilization. (Circulation Research 1990;66:259-270) V arious psychological risk factors have been related epidemiologically to cardiac rhythm disturbances in the presence and absence of coronary artery disease.1-6 These rhythm disturbances include ventricular tachycardia and ventricular fibrillation (VF), the underlying mechanisms of sudden cardiac death. Although some of the psychological stressors are clearly related to acute phasic stress and imminent emotional distress accompanied by hemodynamic alterations consistent with autonomic imbalance, many are related to more tonic From the section of Cardiovascular Sciences (G.W.P., L.H.M.,

Beta-Blockade Restores Muscle Sympathetic Rhythmicity in Human Heart Failure

“…18 Experimental evidence suggests that this reduction in sudden death can be attributed primarily to central, rather than peripheral β-adrenoceptor antagonism. 39 Importantly, in the present series the average dose of carvedilol was well above the threshold demonstrated previously to reduce transcardiac NE spillover and improve survival. 40 Restoration of MSNA spectral power may represent a novel, additional mechanism by which CHF treatment with these 2 β-adrenoceptor antagonists could improve survival in general, and reduce the incidence of sudden death in particular.…”

Selective β1-Blockade Improves Cardiac Bioenergetics and Function and Decreases Neuroendocrine Activation in Rats during Early Postinfarct Remodeling

“…In this study, however, selective ␤ 1 -blockade with metoprolol inhibited significantly sympathetic activation. Suppression of sympathetic activation directly at the level of the central nervous system (33) and/or indirectly due to functional improvement acts in synergy with blockade of ␤ 1 -receptors in myocardium. This synergism is important in cardioprotection from catecholamine toxicity (31) and may directly contribute to the maintenance of integrity of the cellular energetic system.…”

Neuro-cardiac interaction in malignant ventricular arrhythmia and sudden cardiac death

“…Acute ischaemia with coronary artery occlusion is associated with a surge in sympathetic discharge and has been shown to reduce the threshold for VF (i.e. increased susceptibility to VF), an effect which is prevented by pre-treatment with β-adrenergic blockers (Parker et al 1990). In contrast, it has been known for over 100 years since the work of Einbrodt and his 'inductorium' that vagal stimulation increases the threshold for VF, i.e.…”