Michael F. O’Rourke

Time domain analysis of the arterial pulse in clinical medicine

The arterial pulse at any site is created by an impulse generated by the left ventricle as it ejects blood into the aorta, together with multiple impulses travelling in the opposite direction from reflecting sites in the peripheral circulation. The compound wave at any site depends on the pattern of ventricular ejection, the properties of large arteries, particularly their stiffness (which determines rate of propagation) and the distance to and impedance mismatch at reflecting sites. Physicians are familiar with waveform analysis in the time domain, as in the electrocardiogram (ECG) where the principal features are explicable on the basis of atrial depolarisation followed by ventricular depolarisation, then repolarisation. Effects of cardiac functional and structural disease can be inferred from the ECG. It is more difficult to make similar interpretations from the pulse waveform and clinicians usually use this only to count heart rate, extremes of the pressure pulse to express systolic and diastolic pressure, and (sometimes) time from wave foot to incisural notch to measure time of systole and diastole. More information can be gleaned from the shape of the arterial pressure wave through consideration of the factors which create it—on stiffening of large arteries with age, effects of drugs on smallest arteries, and changes in such arterial properties on left ventricular load and function. Such is a major challenge to future physicians. It is aided by better and more accurate methods for measuring flow and diameter as well as pressure waveforms, and by appropriate use of other analytic techniques such as analysis of the pulse in the frequency domain.

Arterial Stiffening in Perspective: Advances in Physical and Physiological Science Over Centuries

Arterial stiffening is not a new issue in medicine or research but was the prime concern of Richard Bright in the early 19th century and of the prominent London physicians and pathologists who tried to unscramble the relationship between kidney, heart, and cerebrovascular disease and hardness of the pulse in the late 19th century. It was of major concern to medical educators including Osler and Mackenzie who were still active in practice 100 years ago. It is all too easy (when dependent on the Internet) to consider arterial stiffness to be a new issue. The terms arterial stiffness, aortic stiffness, or wave reflection do not appear as categories for articles such as this in respectable journals, nor in categories for meetings of specialized physicians. Yet as described in this article, the subject was of interest to clinicians, to investigators such as Harvey in the 17th century, and to physicists who developed laws and principles of elasticity from the study of biological materials including ligaments and arteries. This paper provides a perspective on arterial stiffness from the time of William Harvey and Isaac Newton to the present, with a glance into the future.

Timing and Amplitude of Wave Reflection

To the Editor: Dr Mitchell is to be complemented on a perceptive, articulate editorial on detection and interpretation of wave reflection in the human arterial system.1 While we have differed in the past, modification of 2 points would bring his views into line with ours. First, we see no specific implication of “impedance matching” (increasing proximal aortic stiffness with age and unchanged peripheral muscular artery stiffness). Although this could alter amplitude and apparent location of reflection …

Arterial Stiffness, Wave Reflection, Wave Amplification: Basic Concepts, Principles of Measurement and Analysis in Humans

The arterial system has two functions – as a conduit to deliver blood at high pressure to the organs and tissues of the body according to need, and as a cushion, to reduce pulsations generated by the intermittently-pumping left ventricle, so that blood flow through peripheral high and low resistance vascular beds is steady with little residual pulsation (O’Rourke, Chapter 1: Principles and definitions of arterial stiffness, wave reflections and pulse pressure amplification. In: Safar ME, O’Rourke MF (eds) Arterial stiffness in hypertension. Handbook of hypertension, vol 23. Elsevier, Amsterdam, 2006; Nichols et al., McDonald’s blood flow in arteries, 6th edn. Arnold Hodder, London, 2011). The arterial system in man is beautifully suited to serve these functions, at least through childhood, adolescence and young adulthood (Taylor, Gastroenterology 52:358–363, 1967). By mid-life, effects of pulsatile strain on non-living elastic fibres in the highly pulsatile aorta lead to their fracture and to progressive passive aortic dilation, with transfer of stress to more rigid collagen fibres in the media (Nichols et al., McDonald’s blood flow in arteries, 6th edn. Arnold Hodder, London, 2011). Such changes have adverse effects on arterial function and ideal timing of vascular/ventricular interaction (O’Rourke and Nichols, Hypertension 45:652–658, 2005; Laurent et al., Eur Heart J 27:2588–2605, 2006; O’Rourke and Hashimoto, J Am Coll Cardiol 50:1–13, 2007). As later years pass, impaired arterial function plays an important role in morbidity and mortality, becoming a key factor in development of Isolated Systolic Hypertension of the Elderly (ISHE), and cardiac failure (Chirinos et al. 2012; Weber et al. 2013) and of cerebral micro-infarcts and hemorrhage with cognitive impairment and dementia (O’Rourke and Safar ME, Hypertension 46:200–204, 2005; Stone, Med Hypotheses 71:347–359, 2008; Gorelick, Stroke 42:2672–2713, 2011). This introductory chapter discusses mechanisms and introduces strategies for treatment and prevention.

The Relationship Between Aortic Stiffness, Microvascular Disease in the Brain and Cognitive Decline: Insights into the Emerging Epidemic of Alzheimer’s Disease

The leading current hypothesis of age-related dementia (Alzheimer’s disease) considers this a consequence of the beta-amyloid peptide or of the intracellular skeletal protein tau, causing breakdown of the cerebral capillary bed. External trauma to the head in boxing and football is known to induce similar dementia ( dementia pugilistica, chronic traumatic encephalopathy), usually showing onset years after the individual’s retirement from active sport. At autopsy in dementia pugilistica, haemorrhage from cerebral vessels is prominent. This presentation reviews evidence that age-related dementia (ARD) is caused by internal trauma to vascular bed of the brain, by the pulse itself. Between the ages of 50 and 80 years, the heart beats ~109 times and, because of the low impedance of the cerebral circulation, each pulse penetrates to the cerebral veins. Further, the stiffness of the walls of the aorta and great arteries increases with age; and the amplitude of the pressure pulse in cerebral vessels (a measure of the cerebral pulse intensity) increases several fold. This pounding of cerebral vessels by the pulse induces (we argue) haemorrhages from cerebral vessels. When the vessel that haemorrhages is large, the patient may display symptoms of stroke and any resulting dementia is designated ‘vascular’. When the vessels that haemorrhage are small (capillaries), the patient may experience no acute symptoms; but the cumulative effect of many such haemorrhages becomes evident as loss of memory and of cognition. The pathologies which Alzheimer described in the demented brain (senile plaques, neurofibrillary tangles and inflammation) occur, we argue, as a result of haemorrhage. The age at which dementia becomes evident is determined by the fragility of cerebral vessels, which may vary between individuals with genetic and lifestyle factors. The hypothesis accounts better than previous proposals for the greatest risk factor for dementia – age.

Nitrate: The Ideal Drug Action for Isolated Systolic Hypertension in Elderly?

Nitrates such as nitroglycerine and isosorbide mononitrate are unique drugs, and at least in theory ideal for treating Isolated Systolic Hypertension in the Elderly (ISHE). Early wave reflection from aortic stiffening increases late systolic pressure in the ascending aorta and left ventricle, and is the cause of ISHE, but diastolic pressure and mean pressure are normal. Nitrates decrease or abolish wave reflection from peripheral arterioles, “trapping” this within the peripheral arterial networks (Yaginuma et al. Cardiovasc Res 20:153–160, 1986).

Long-Term Effects of Calcium Channel Blockers on Central and Peripheral Arteries

Calcium channel blockers (CCBs) are reported to be more effective in reducing cerebrovascular events than other antihypertensive drugs in hypertensive patients. Large artery stiffness could be partly reduced through the reduction of the distending pressure and arterial structural changes by long-term treatment with CCBs. Because CCBs reduce the magnitude of wave reflection by attenuating the vascular tone of peripheral muscular arteries, CCBs cause a greater fall in the central aortic pressure than did β-blockers or diuretics, despite no difference in peripheral (brachial) pressure. The de-stiffening of the large arteries and the dilation of peripheral muscular arteries by CCBs might be underlying mechanisms of the significant reductions in central pressure and blood pressure variability, thus reducing carotid atherosclerosis, cerebral arteriosclerotic damage, and cerebrovascular events in hypertensive patients.

The Proximal Thoracic Aorta : Keystone or Achilles’ Heel?∗

The proximal thoracic aorta—composed of the ascending aorta, aortic arch, and upper descending aorta—plays the major role in accepting blood from the left ventricle (LV), cushioning flow pulsations and passing blood to the body’s tissues and organs with minimal energy loss [(1)][1]. The load