8th CONFERENCE OF THE EUROPEAN STUDY GROUP ON CARDIOVASCULAR OSCILLATIONS (ESGCO 2014)

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Abstract — Variability in arterial pressure and cerebral blood flow has traditionally been interpreted as a marker of cardiovascular decompensation, and has been associated with negative clinical outcomes across varying time scales, from impending orthostatic syncope to an increased risk of stroke. Emerging evidence, however, suggests that increased hemodynamic variability may, in fact, be protective in the face of acute challenges to perfusion, including significant central hypovolemia and hypotension (including hemorrhage), and during cardiac bypass surgery. We present the dichotomous views on the role of hemodynamic variability on clinical outcome, including the physiological mechanisms underlying these patterns, and the potential impact of increased and decreased variability on cerebral perfusion and oxygenation. We suggest that reconciliation of these two apparently discrepant views may lie in the time scale of hemodynamic variability; short time scale variability appears to be cerebroprotective, while mid to longer term fluctuations are associated with primary and secondary end-organ dysfunction.

I. INTRODUCTION Traditionally, clinicians have assessed the cardiovascular

status of their patients with static “snapshot” techniques, such as radial pulse for heart rate, brachial sphygmomanometry for arterial pressure, and chest excursions for respiration rate. Subsequently, clinical judgment about health status and identification of potential risk factors was based on average values, without consideration of the inherent dynamic nature of these variables. There is now growing recognition that assessment of hemodynamic variability (e.g., heart rate and arterial pressure) across multiple time scales may provide important insight into acute and long-term clinical outcomes, such as risk of stroke [1], myocardial infarction [2], and end organ damage from hypertension [3]. With advances both in monitoring technologies and data analysis capabilities, we now have the capacity to capture dynamic changes in patient status by recording and analyzing non-invasive, high frequency hemodynamic waveform data, including ECG, arterial pressure, and most recently, cerebral blood flow (via transcranial Doppler (TCD) ultrasound) and oxygenation (via near infra-red spectroscopy, NIRS). These high fidelity recordings have advanced assessment of hemodynamic

Research supported, in part, by the US Army Medical and Materiel

Command (CAR), and the New Zealand Health Research Council (YCT). C. A. Rickards is with the University of North Texas Health Science

Center, USA (*corresponding author e-mail: caroline.rickards@unthsc.edu).

Y-C. Tzeng is with the University of Otago, New Zealand.

variability from intermittent day-to-day or visit-to-visit measures, to a beat-to-beat time scale.

Consequently, cerebral blood flow variability has been extensively examined in the research setting in an effort to understand underlying regulatory mechanisms, particularly the role of adrenergic, cholinergic, and myogenic modulation of the cerebral vasculature with changes in arterial pressure. Assessment of cerebral blood flow variability in the clinical setting, however, has lagged the abundance of studies investigating the role of blood pressure variability (BPV), despite clear implications for the subsequent integrity of cerebral tissues [4]. Furthermore, the potential role of increased variability in arterial pressure and cerebral blood flow on clinical outcome is somewhat disparate, with studies suggesting both protective and detrimental effects.

II. METHODS We present data from the literature briefly describing the

harmful (fig. 1) versus potentially protective effects (fig. 2 & 3) of variability in arterial pressure and cerebral blood flow.

III. RESULTS

Fig. 1 Relationship between the severity of organ damage and 24 h systolic blood pressure (SBP) (a) and, its variability (SBPV) in the short (b) and long term (c) in spontaneously hypertensive rats at 60 weeks of age. [Data from Su et al. [5], with permission].

Fig. 2 Mean middle cerebral artery velocity (MCAv), and MCAv low frequency (LF) power during progressive central hypovolemia induced by lower body negative pressure (LBNP) while breathing through a sham or active inspiratory threshold device (ITD). Breathing through an ITD further decreases intra-thoracic pressure upon inspiration, subsequently increasing venous return and stroke volume. [Data modified from Rickards et al. [6]]. *, p<0.05 compared with baseline; †, p<0.05 compared with sham ITD condition.

Blood Pressure and Cerebral Blood Flow Oscillations: Friend or Foe?

Caroline A. Rickards*, and Yu-Chieh Tzeng

8th CONFERENCE OF THE EUROPEAN STUDY GROUP ON CARDIOVASCULAR OSCILLATIONS (ESGCO 2014)

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Fig. 3 Low frequency (LF) power in mean arterial pressure (MAP; top), and mean middle cerebral artery velocity (MCAv; bottom) as a function of progressive hypovolemia via application of lower body negative pressure (LBNP). Dashed line represents the separation of low tolerant (LT) and high tolerant (HT) subjects. [Data modified from Rickards et al., [7]].

IV. DISCUSSION “Foe” As the brain has a high metabolic demand for

oxygen, any process that increases perfusion variability has the potential to destabilize tissue oxygenation, leading to ischemic injury. The case for exaggerated hemodynamic variability being a negative predictor for organ dysfunction is primarily built on studies of BPV, particularly mid- to longer-term variations (fig. 1). These effects include enhanced propensity for atherosclerosis progression [8], increased arterial stiffness [9], left ventricular hypertrophy [10], cognitive dysfunction in the elderly [11], and increased presence of cerebral micro-bleeds and white matter hyper-intensities on MRI [12]. While there are limited studies investigating the role of BPV on cerebral blood flow variability, and the subsequent effect on cerebral tissue integrity and perfusion dysfunction, this is a burgeoning area of research interest.

“Friend” In contrast, pulsatile cerebral blood flow at or around the cardiac frequency (≥ 1 Hz) has been associated with decreased neuronal damage following prolonged cardiac arrest in dogs [13], improved cerebral oxygen uptake following cerebral ischemia in pigs [14], and increased microcirculatory perfusion and increased oxygen consumption in patients undergoing coronary artery bypass surgery [15]. Furthermore, low frequency (LF, ~0.1 Hz) pulsatile cerebral blood flow has recently been associated with increased tolerance to experimentally induced central hypovolemia (i.e., simulated hemorrhage) in healthy human subjects, despite ≥30% reductions in absolute cerebral blood flow [6, 7], both with (fig. 2) and without (fig. 3) an inspiratory resistance breathing intervention.

In this brief review we have contrasted evidence that supports hemodynamic variability as a protective feature of physiology against evidence suggesting that hemodynamic variability heralds expansive damage to organ function. Our review suggests that reconciliation of these two apparently discrepant views may lie in the time scale of hemodynamic variability; short time scale variability appears to be cerebroprotective, while mid-to-longer term fluctuations are associated with primary and secondary end-organ dysfunction. The extent to which knowledge of the positive and deleterious influences of hemodynamic variability will

lead to improve health outcomes are presently unknown, but the case is mounting against classical approaches to hemodynamic assessment that focuses narrowly on absolute blood pressure and/or cerebral blood flow.

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