COMMENTARY The roles of a- and b-adrenoceptor stimulation in myocardial ischaemia K. J. Broadley & P. E. Penson Division of Pharmacology, Welsh School of Pharmacy, Cardiff University, King Edward VII Avenue, Cardiff CF10 3XF, UK Summary 1 b-Adrenoceptor (AR) ligands have been the mainstay of cardiovascular therapy for decades, with b-AR antagonist being used for hypertension, angina and myocardial infarction and adrenaline in use for cardiopulmonary resuscitation for nearly 100 years. 2 Ischaemia of the heart through coronary artery occlusion causes cell injury and death through necrosis and apoptosis. Reperfusion of the ischaemic myocardium results in cardiac dysfunction and infarction. 3 Stimulation of a- and b-ARs in the ischaemic heart have variable and inconsistent effects depending on when the agonist is applied. This review describes the different effects of stimulation of the three established b-AR subtypes (b 1 -, b 2 - and b 3 -ARs) either before ischaemia (preconditioning) or during ischaemia and reperfusion of the heart (postconditioning). 4 Brief periods of ischaemia preceding a major ischaemic episode can have a protective effect against post-ischaemia–reperfusion damage, known as ischaemic preconditioning. This review considers the role of endogenous catecholamines released during preconditioning and the nature of the adrenoceptor subtypes that mediate these effects. The clinical significance of this to the use of b-AR antagonists is considered. 5 The transduction pathways and effects on apoptosis of the cardioprotective and deleterious effects of AR activation are considered. 6 This commentary reviews the literature and attempts to bring together a unified synopsis of the effects of adrenoceptor stimulation in myocardial ischaemia and the potential clinical relevance. Keywords: b-adrenoceptor, a-adrenoceptor, myocardial ischaemia, myocardial infarction, preconditioning, cardiopulmonary resuscitation Introduction This paper serves as a mini-review on the roles of adrenoceptors (AR) in the ischaemic heart. Adreno- ceptor agonists and antagonists have been used since the beginning of the 20th century for the treatment and alleviation of cardiovascular disor- ders. Agonists have been used to stimulate the heart as a means of cardiopulmonary resuscitation (CPR) in acute cardiac arrest and to improve contractile function following a myocardial infarction. Antag- onists are widely used in cardiovascular disease to treat hypertension and coronary vascular disease including angina pectoris and myocardial infarc- tion, and more recently they have been advocated for the treatment of congestive cardiac failure. Here we review the literature on cardiac a- and b-adrenoceptors and the effects of their stimulation before, during and after ischaemia. This article presents a commentary on whether they exert protective or detrimental effects on post-ischaemic myocardial function, including cardiac contractil- ity, dysrhythmias and the extent of infarct damage. Cardiopulmonary resuscitation Cardiac arrest associated with ventricular fibrilla- tion and asystole requires immediate CPR of the 87 Autonomic & Autacoid Pharmacology, 24, 87–93 Ó 2004 Blackwell Publishing Ltd Correspondence: K. J. Broadley