The role of heart rate and the benefits of heart rate reduction in acute myocardial ischaemia

In myocardial ischaemia, detailed analyses of experimental data show that regional myocardial blood flow and contractile function are reduced proportionately—this being contrary to the common notion that the underlying pathological mechanism is a supply/demand imbalance. Such perfusion–contraction matching is maintained at an increased heart rate. In the normal myocardium, metabolic regulation prevails and tachycardia results in an increased coronary blood flow. In post-stenotic myocardium that has an exhausted dilator reserve, a reduction in diastolic duration prevails, and coronary blood flow is decreased with tachycardia. In the presence of collaterals, both metabolic vasodilation of the normal microcirculation and reduced diastolic duration act in concert to decrease collateral perfusion pressure and collateral flow into the post-stenotic coronary microcirculation. Tachycardia results from sympathetic activation and activation of beta-adrenoceptors. Accordingly, beta-adrenergic blockers have been used to treat patients with stress-induced myocardial ischaemia. The benefits of heart rate reduction by beta-blockade are in part counterbalanced by unmasked alpha-adrenergic coronary vasoconstriction. Selective heart rate-reducing agents can decrease heart rate without unmasking alpha-adrenergic coronary vasoconstriction. They improve the blood flow distribution into the ischaemic myocardium and, as a consequence, improve regional myocardial function. Ivabradine is the only clinically available selective heart rate-reducing agent, and it exerts anti-ischaemic actions in patients with chronic stable angina.