Autoregulation of Chronotropic Response of the Heart Through Pacemaker Stretch

Pathak, C. L.

doi:10.1159/000169618

Cited by 54 publications

(12 citation statements)

References 24 publications

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“…In 1915, Francis Arthur Bainbridge observed that intravenous fluid injection in anaesthetised dogs resulted in right-atrial distension and an increase in BR (Bainbridge, 1915). He described this as an “ Acceleration of heart rate […] caused by impulses arising within the heart .” Similar effects have since been observed in various vertebrate phyla, including Amphibia , Reptilia , Aves , and Mammals (Pathak, 1973). Confirming this finding in humans proved difficult, initially, as most non-invasive interventions that raise central venous pressure in human (such as tilt-table studies) also increase arterial pressure.…”

Section: Direct Mechanical Effects On Cardiac Pacemaker Activitysupporting

confidence: 67%

Mechano-sensitivity of cardiac pacemaker function: Pathophysiological relevance, experimental implications, and conceptual integration with other mechanisms of rhythmicity

Quinn

Kohl

2012

Progress in Biophysics and Molecular Biology

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Cardiac pacemaker cells exhibit spontaneous, rhythmic electrical excitation, termed automaticity. This automatic initiation of action potentials requires spontaneous diastolic depolarisation, whose rate determines normal rhythm generation in the heart. Pacemaker mechanisms have been split recently into: (i) cyclic changes in trans-sarcolemmal ion flows (termed the ‘membrane-clock’), and (ii) rhythmic intracellular calcium cycling (the ‘calcium-clock’). These two ‘clocks’ undoubtedly interact, as trans-sarcolemmal currents involved in pacemaking include calcium-carrying mechanisms, while intracellular calcium cycling requires trans-sarcolemmal ion flux as the mechanism by which it affects membrane potential. The split into separate ‘clocks’ is, therefore, somewhat arbitrary. Nonetheless, the ‘clock’ metaphor has been conceptually stimulating, in particular since there is evidence to support the view that either ‘clock’ could be sufficient in principle to set the rate of pacemaker activation.Of course, the same has also been shown for sub-sets of ‘membrane-clock’ ion currents, illustrating the redundancy of mechanisms involved in maintaining such basic functionality as the heartbeat, a theme that is common for vital physiological systems.Following the conceptual path of identifying individual groups of sub-mechanisms, it is important to remember that the heart is able to adapt pacemaker rate to changes in haemodynamic load, even after isolation or transplantation, and on a beat-by-beat basis. Neither the ‘membrane-’ nor the ‘calcium-clock’ do, as such, inherently account for this rapid adaptation to circulatory demand (cellular Ca2+ balance changes over multiple beats, while variation of sarcolemmal ion channel presence takes even longer). This suggests that a third set of mechanisms must be involved in setting the pace. These mechanisms are characterised by their sensitivity to the cyclically changing mechanical environment, and – in analogy to the above terminology – this might be considered a ‘mechanics-clock’.In this review, we discuss possible roles of mechano-sensitive mechanisms for the entrainment of membrane current dynamics and calcium-handling. This can occur directly via stretch-activation of mechano-sensitive ion channels in the sarcolemma and/or in intracellular membrane compartments, as well as by modulation of ‘standard’ components of the ‘membrane-’ or ‘calcium-clock’. Together, these mechanisms allow rapid adaptation to changes in haemodynamic load, on a beat-by-beat basis.Additional relevance arises from the fact that mechano-sensitivity of pacemaking may help to explain pacemaker dysfunction in mechanically over- or under-loaded tissue. As the combined contributions of the various underlying oscillatory mechanisms are integrated at the pacemaker cell level into a single output – a train of pacemaker action potentials – we will not adhere to a metaphor that implies separate time-keeping units (‘clocks’), and rather focus on cardiac pacemaking as the result of interactions of a set of coupled osci...

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Section: Direct Mechanical Effects On Cardiac Pacemaker Activitysupporting

confidence: 67%

Mechano-sensitivity of cardiac pacemaker function: Pathophysiological relevance, experimental implications, and conceptual integration with other mechanisms of rhythmicity

Quinn

Kohl

2012

Progress in Biophysics and Molecular Biology

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“…Mechanical effects on the sinus node might explain the responses to tilting and Valsalva's maneuver. 4 Exercise to the maximum levels possible in our patient increased heart rate by 11 beats per minute. In the transplanted human heart the rate is barely affected by mild exercise, but during prolonged exercise the rate may increase almost as much as in the normal heart.…”

Section: Discussionmentioning

confidence: 51%

Total Cardiac Denervation in Diabetic Autonomic Neuropathy

Lloyd‐Mostyn

Watkins

1976

Diabetes

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“…9,29) This result was confirmed in a largescale trial conducted by Cole, et al 6) Several mechanisms have been proposed for the attenuation of HRR in coronary artery disease patients, such as an imbalance between sympathetic withdrawal and parasympathetic activation, the alteration of venous return, or stretch in the atrial wall. [1][2][3][4][5] The mechanism underlying the attenuation of HRR in heart failure patients may be much more complicated. The decreased resting vagal tonus, increased resting and exercise sympathetic tonus, and attenuation of autonomic regulatory mechanisms by increasing age are possible mechanisms proposed for the attenuation of HRR in heart failure patients.…”

Section: Discussionmentioning

confidence: 99%

Decreased Heart Rate Recovery in Patients With Heart Failure Effect of Fluvastatin Therapy

et al. 2005

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SUMMARYHeart rate recovery is the difference in heart rate at peak exercise and at a specific time interval following the onset of recovery. Attenuated heart rate recovery is an independent predictor of mortality in patients with a history of coronary artery disease. The aim of the present study was to evaluate the effect of a statin on heart rate recovery, particularly in patients with ischemic heart failure and hyperlipidemia. Twenty-nine consecutive hyperlipidemic, stable coronary artery disease patients with heart failure and 19 healthy subjects were enrolled. Heart rate recovery values at the 1st and 3rd minutes and lipid profiles of the patients were evaluated at baseline and following 3 months of treatment with fluvastatin. Compared with healthy subjects, the heart rate recovery values were significantly lower in the heart failure patients in both the 1st and 3rd minutes, respectively (31 ± 6 versus 19 ± 7, P < 0.0001; 66 ± 7 versus 47 ± 8, P < 0.0001). Heart rate recovery in the 1st and 3rd minutes increased from 19 ± 7 to 24 ± 9 and 47 ± 8 to 57 ± 11, respectively, following treatment (P < 0.001, P < 0.001). There were no significant correlations among the changes in lipid parameters or HRR in the first and third minutes in the recovery period. The results revealed an improvement in heart rate recovery in heart failure patients by fluvastatin treatment. If this association can be confirmed by other studies, it would be interesting to perform further studies into the mechanism underlying this finding. (Int Heart J 2005; 46: 845-854)

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Autoregulation of Chronotropic Response of the Heart Through Pacemaker Stretch

Cited by 54 publications

References 24 publications

Mechano-sensitivity of cardiac pacemaker function: Pathophysiological relevance, experimental implications, and conceptual integration with other mechanisms of rhythmicity

Mechano-sensitivity of cardiac pacemaker function: Pathophysiological relevance, experimental implications, and conceptual integration with other mechanisms of rhythmicity

Total Cardiac Denervation in Diabetic Autonomic Neuropathy

Decreased Heart Rate Recovery in Patients With Heart Failure Effect of Fluvastatin Therapy

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