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

Abstract

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. b-Blockade improves both flow and function along this relationship. When the heart rate reduction associated with b-blockade is prevented by pacing, a-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 a-adrenergic coronary vasoconstriction or negative inotropic action.

Arrhythmogenic Effect of Sympathetic Histamine in Mouse Hearts Subjected to Acute Ischemia

“…One possible reason for this is that NE, which is released simultaneously, plays an important role in triggering the rise of cardiac cAMP levels, via postsynaptic β 1 adrenoreceptors and in inducing positive chronotropic and in- otropic effects. This is the basis for the clinical use of β adrenoreceptor antagonists in the treatment of ischemia-induced arrhythmias (37). The finding that the selective β 1 adrenoreceptor antagonist atenolol used independently exhibited a similar antiarrhythmic effect to famotidine but when used in combination, a stronger antiarrhythmic effect was observed, confirms the hypothesis that cardiac sympathetic HA facilitates the arrhythmogenic effect of NE.…”

Role of heart rate in mechanisms of compensation and decompensation in patients with CHF and sinus rhythm or atrial fibrillation and methods for safe and effective control of the heart rhythm. Part 1. Sinus rhythm

“…При этом укорачивается время диастолического наполнения желудочков сердца, что по закону Франка-Старлинга сопровождается допол-нительным уменьшением УО [21]. Одновременно падает вклад сократимости предсердий в эффектив-ную работу сердца, особенно при развивающейся фибрилляции предсердий [22,23]; • в-третьих, вследствие короткой диастолы уменьша-ется время коронарной перфузии и кровоснабжения миокарда желудочков [24], что особенно неблагопри-ятно для пациентов с ишемической этиологией ХСН (около 70 % больных ХСН с низкой ФВ ЛЖ) [25].…”

Therapy for Angina Pectoris Secondary to Coronary Disease

“…Indeed, heart rate is the major determinant of myocardial oxygen demand and its increase is a precipating factor for ischemia or angina (Andrews et al, 1993;Borer et al, 2003;Daly et al, 2010;Fox et al, 2007;Heusch, 2008;Tardif et al, 2005). Heart rate also predicts outcome in epidemiologic studies of patients with CAD, as well as those with heart failure, hypertension, and, indeed, in unselected free living populations without apparent heart disease (Daly et al, 2010;Diaz et al, 2005;Fox et al, 2007;Tardif et al, 2009).…”

“…Indeed, the United States Food and Drug Administration will not approve a therapy for angina unless both the symptoms and the underlying ischemia are relieved in pre-approval testing because of concerns for patient safety if this symptomatic warning of ischemia is masked and the inciting activity continues. The major determinants of myocardial oxygen demand are heart rate (Fox et al, 2007;Heusch, 2008), systolic blood pressure and contractility. Indeed, experimentally, a twofold increase in any of these determinants of oxygen consumption requires approximately 50% increase in coronary blood flow if ischemia is to be avoided (Libby et al, 2008).…”