Impaired β-adrenergic receptor signalling in post-resuscitation myocardial dysfunction

Objective: Post-resuscitation myocardial dysfunction is a major cause of fatality in patients receiving successful cardiopulmonary resuscitation. The mechanism of post-resuscitation myocardial dysfunction is largely unknown, although is generally considered related to ischaemia occurring during cardiac arrest and resuscitation and/or reperfusion injury after restoration of circulation. A key mechanism responsible for reduced contractile reserves in chronic heart failure is impaired beta-adrenergic receptor signalling. Thus, we hypothesised that beta-adrenergic receptor signalling is markedly abnormal in the post-resuscitation period following cardiopulmonary resuscitation. Methods: Male landrace domestic pigs were randomised into a sham group (anaesthetised and instrumented, no ventricular fibrillation) or cardiopulmonary resuscitation (CPR) group (ventricular fibrillation) (n = 8 per group). Haemodynamic and echocardiographic data were recorded. beta-Adrenergic receptor signalling was assessed at 6 h after the operation by measuring myocardial adenylate cyclase activity, beta-adrenergic receptor density and beta-adrenergic receptor kinase expression. Results: Left ventricular function in the CPR group was significantly decreased at 6 h after restoration of spontaneous circulation. Basal and isoproterenol-stimulated adenylate cyclase activity was blunted in the CPR group compared with the sham group. Total beta-AR density was significantly decreased in CPR group compared with the sham group. Myocardial beta-adrenergic receptor kinase expression was 2.03-fold greater in the CPR group than in the sham group. Conclusions: beta-Adrenergic receptor signalling is markedly impaired in the post-resuscitation period, which may be a mechanism of post-resuscitation myocardial dysfunction. (c) 2011 Elsevier Ireland Ltd. All rights reserved.