Heart-rate reduction and -blockade in early post-infarction cardiac remodelling

Abstract

Soon after acute myocardial infarction, the heart may experience extensive changes in function, structure, tissue architecture, and biochemical properties collectively known as cardiac remodelling. Many of the deleterious changes can be attenuated by treatment with β-adrenergic blocking agents1–3 or with alternative drugs that reduce post-infarction heart rate without interrupting β-adrenergic signalling.4,5 In a study appearing in this issue of Cardiovascular Research ,6 Mączewski and Mackiewicz employed a rat model to elucidate the benefits of post-infarction β-blockade by comparing effects of heart-rate reduction without β-blockade (using ivabradine) and effects observed when the same reduction in heart rate was combined with β-blocking action (using metoprolol). Drug treatment was begun 24 h after coronary ligation and halted 48 h before final measurements. Thus, outcomes reflected drug manipulation of early remodelling after the acute ischaemic insult, and measurements identified effects persisting after drug washout and dissipation of immediate drug actions on heart rate and β-receptors. Heart-rate reduction appeared impressively beneficial for haemodynamic function, even in the absence of concomitant β-blockade: improvement in contractility (ejection fraction and +d P /d t ) and filling pressures (left ventricular end-diastolic pressures and lung congestion) were equivalent in rats receiving ivabradine and those receiving metoprolol. … *Corresponding author. Tel: +1 301 295 3601; fax: +1 301 295 3557. E-mail address : rgoldstein{at}usuhs.mil