Heart rate and experimental myocardial ischaemia

Every increase in heart rate represents a poor prognostic factor in cardiology, and multiple arguments have now led to the belief that reducing heart rate is a major therapeutic challenge. A comparison of the pharmacological effects of I-f current inhibitors such as zatebradine, and more recently ivabradine (Procoralan(R)) and beta-blockers, have demonstrated experimentally that reductions in heart rate and myocardial contractile force contribute equally to the reduction in myocardial oxygen consumption in the normal heart. Conversely, at a similar level of reduction in heart rate, the lack of a concomitant negative inotropic effect with ivabradine affords longer diastolic perfusion times than beta-blockers. In other words, a negative inotropic effect is deleterious when an increase in coronary blood flow is required. Hence, if the anti-ischaemic effects afforded by an I-f current inhibitor and a beta-blocker are roughly comparable, the former are clearly of higher benefit than beta-blockers in the treatment of myocardial dysfunction accompanying cardiac ischaemia-reperfusion, especially myocardial stunning.