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Ivabradine in heart failure: NICE guidance
  1. Suzanna M C Hardman
  1. Correspondence to Dr Suzanna M C Hardman PhD, FRCP, Clinical and Academic Department of Cardiovascular Medicine (3A), St Mary's Wing, The Whittington Hospital, Magdala Avenue, London N19 5NF, UK; suzanna.hardman{at}whittington.nhs.net

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Heart rate and the funny channel

In the normal heart the sinus node determines the heart rate.1 Sino-atrial myocytes are characterised by a poorly developed contractile system and self-generating repetitive action potentials, a feature not found in the myocytes of cardiac muscle. At the end of the action potential, depolarisation of the membrane voltage continues, during phase four, until this triggers another action potential. While sino-atrial myocytes are heavily innervated by both sympathetic and vagal nerves, the spontaneous activity is independent of innervation. The mechanisms controlling, or modifying, these spontaneous diastolic depolarisations are central to interventions that might be employed to modify heart rate. Early thinking attributed pacemaker activity to the decay of an outward K+ current, but in the late 1970s Brown et al identified, to their surprise, a new likely inward current accordingly described as a ‘funny current or If’.2

Although many questions remain unanswered,3 If is now recognised as an Na/K inward current activated by hyperpolarisation and modulated by the autonomic nervous system. Adrenaline induced rate acceleration in sino-atrial myocytes is almost entirely due to shortening of the diastolic duration with minimal effect on action potential shape and duration2 in contrast to adrenalin-mediated influences on cardiac action potentials elsewhere. Vagal influences are similarly associated with slowing of phase four of the sino-atrial myocytes rather than influencing the morphology elsewhere. There appears to be upregulation of the If channel in cardiac hypertrophy and heart failure (HF).4 ,5

But why might this be of interest?

While there is extensive evidence that a slower heart rate is associated with better outcomes, be that as a marker of overall fitness in the general population,6 ,7 in people with a range of cardiovascular conditions,8–10 in HF specifically,11 ,12 or to the diverse therapeutic effects of β-blockers in HF,13 , …

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