Intrapericardial β-Adrenergic Blockade with Esmolol Exerts a Potent Antitachycardic Effect Without Depressing Contractility

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Abstract
Hyperadrenergic states of various etiologies can contribute to tachycardias. Systemic beta-adrenergic blockade suppresses sinus tachycardia but may adversely affect arterial blood pressure and contractility, because the drug gains access to myocardial cells as well as to the sinoatrial node. We examined whether intrapericardial beta-adrenergic blockade with esmolol could suppress tachycardia without reducing contractility as a result of limited drug diffusion, which would be sufficient to penetrate the superficial sinoatrial node but not the deeper myocardial layers. In five anesthetized pigs, we provoked a reflex heart rate increase of 50 beats/min with hemorrhage. The rapidly acting beta-adrenergic blocking agent esmolol (1 mg/kg) was administered intrapericardially using a new percutaneous transatrial access method and a catheter system that can be rapidly and safely introduced. Esmolol equivalently suppressed hemorrhage-induced sinus tachycardia when administered intrapericardially (from 192 to 158 beats/min at 5 min, p < 0.05) or intravenously (from 177 to 151 beats/min at 1 min, p < 0.05). The antitachycardic effect of intrapericardial esmolol was prolonged compared with intravenous esmolol (10 min vs. 3 min, p < 0.05). Intrapericardial esmolol did not affect blood pressure or left ventricular dP/dt max, an index of contractility, whereas intravenous esmolol decreased blood pressure at 1 min for 2 min (p < 0.05) and simultaneously decreased left ventricular dP/dt max at 1 min for < 2 min (p < 0.05). Intrapericardial esmolol suppresses adrenergically induced sinus tachycardia without decreasing contractility or blood pressure. The transatrial approach for intrapericardial delivery of certain 1-adrenergic blocking agents could be employed to control tachycardias in emergency care and surgical settings in patients with impaired cardiac contractility and propensity to hypotension.

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