Heart rate in the pathophysiology of coronary blood flow and myocardial ischaemia: benefit from selective bradycardic agents

Starting out from a brief description of the determinants of coronary blood flow (perfusion, pressure, extravascular compression, autoregulation, metabolic regulation, endothelium‐mediated regulation and neurohumoral regulation) the present review highlights the overwhelming importance of metabolic regulation such that coronary blood flow is increased at increased heart rate under physiological circumstances and the overwhelming importance of extravascular compression such that coronary blood flow is decreased at increased heart rate through reduction of diastolic duration in the presence of severe coronary stenoses. The review goes on to characterize the role of heart rate in the redistribution of regional myocardial blood flow between a normal coronary vascular tree with preserved autoregulation and a poststenotic vasculature with exhausted coronary reserve. When flow is normalized by heart rate, there is a consistent close relationship of regional myocardial blood flow and contractile function for each single cardiac cycle no matter whether or not there is a coronary stenosis and what the actual blood flow is. β‐Blockade improves both flow and function along this relationship. When the heart rate reduction associated with β‐blockade is prevented by pacing, α‐adrenergic coronary vasoconstriction is unmasked and both flow and function are deteriorated. Selective heart rate reduction, however, improves both flow and function without any residual negative effect such as unmasked α‐adrenergic coronary vasoconstriction or negative inotropic action. British Journal of Pharmacology (2008) 153 , 1589–1601; doi: 10.1038/sj.bjp.0707673 ; published online 28 January 2008