Measuring the rate of change of haemodynamic response at the onset of exercise in normal limbs and those with intermittent claudication

Patients with claudication have an inadequate haemodynamic response to exercise. Blood flow response will not only have a magnitude, but also a rate of change. There is scope for investigating these parameters, as manipulation of the factors which control them may benefit work to improve the treatment for claudication. This work compares the responses for patients with one normal limb and one with intermittent claudication. A custom-built ergometer allows unilateral, infragenicular plantar flexion exercise, whilst common femoral artery blood flow can be measured continuously by Duplex ultrasound. This apparatus was used to measure blood flow before, at the onset of and during a 5 W square-wave exercise stimulus in 15 patients. The claudicant group had a mean steady-state gain that was approximately half that of the normal group at around 170 ml min(-1) (p < 0.001) and a response time that was much shorter (p = 0.006). A mean response time of 21.0 +/- 1.4 s was achieved in claudicant limbs compared to 31.8 +/- 2.9 s in normals. However, the average rate of change of blood flow during this response time was estimated to still be greater for the normal group, at 431.7 +/- 47.1 ml min(-2), than for the claudicant group. The differences in magnitude and rate of change of limb blood flow response to exercise in claudicants were significant and may have implications for the treatment of claudication.     

Effects of physical training in intermittent claudication

Mechanisms for increased claudication distance following physical training were studied in ten patients with peripheral arterial insufficiency. The exercise capacity on a bicycle ergometer increased by an average of 26% after 3--4 months of training (P less than 0.05). Neither maximum lower leg blood flow during the exercise test nor oxygen uptake at exhaustion changed significantly after training (-8% and +5%, respectively), whereas popliteal-venous O2-saturation was lower at exhaustion after the training than before (8.5 +/- 3.2 and 11.4 +/- 4.6, respectively, P less than 0.05). Anaerobic glycolysis, as evidenced by the lactate release, was also lowered after the training (P less than 0.05). In conclusion, the present study shows that the increased exercise capacity following physical training in claudicants is associated with an increased local aerobic working capacity despite a virtually unchanged blood flow. This increased aerobic exercise capacity might partly be explained by an increased O2 extraction in the lower leg during exercise.     

Oxygen uptake-to-delivery relationship: a way to assess adequate flow

Invasive and noninvasive monitoring facilitates clinical evaluation when resuscitating patients with complex haemodynamic disorders. If the macrocirculation is to be stable, then it must adapt to blood flow or blood flow must be optimized. The objective of flow monitoring is to assist with matching observed oxygen consumption (VO2) to pathophysiological needs. If an adequate balance cannot be maintained then dysoxia occurs. In this review we propose a simple schema for global reasoning; we discuss the limitations of VO2 and arterial oxygen delivery (DaO2) assessment; and we address concerns about increasing DaO2 to supranormal values or targeting pre-established levels of DaO2, cardiac output, or mixed venous oxygen saturation. All of these haemodynamic variables are interrelated and limited by physiological and/or pathological processes. A unique global challenge, and one that is of great prognostic interest, is to achieve rapid matching between observed and needed VO2--no more and no less. However, measuring or calculating these two variables at the bedside remains difficult. In practice, we propose a distinction between three situations. Clinical and blood lactate clearance improvements can limit investigations in simple cases. Intermediate cases may be managed by continuous monitoring of VO2-related variables such as DaO2, cardiac output, or mixed venous oxygen saturation. In more complex cases, three methods can help to estimate the needed VO2 level: comparison with expected values from past physiological studies; analysis of the relationship between VO2 and oxygen delivery; and use of computer software to integrate the preceding two methods.     

Evaluation of Doppler ultrasound for blood perfusion measurements.

The need to develop clinical methods for the noninvasive monitoring of regional blood perfusion, i.e., the blood flow through the very fine capillaries in body tissue, has long been felt. Hitherto existing methods exhibit limitations, such as insufficient measurement depth and poor time- or space-resolution, which restrict the measurements that can be performed. Dymling (1982) introduced a new CW Doppler ultrasound method for noninvasive blood perfusion measurement which might be one possible solution to this problem. Preliminary experiments indicated a correlation between blood flow and measured perfusion value. Unexpectedly large variations in the recorded perfusion values lead to further investigation of the method, both in vitro using a specially designed flow phantom and in vivo. This study indicates that at least some of the large variations recorded are the result of measurement errors caused by movement artifacts or ultrasonic signal interferences. Methods to diminish the effects of these artifacts are discussed.     

Application of a portable microscopic cell counter for the counting of residual leukocytes in leukoreduced apheresis platelet concentrates in a hospital blood bank

While a portable microscopic cell counter has been evaluated to enumerate residual white blood cells (WBCs) in red blood cells and platelet concentrates at blood centers, it has not yet been assessed in a hospital blood bank. We investigated the performance of this device and evaluated its accuracy, along with its benefits in time management.Residual WBCs from each of 100 apheresis platelet specimens were measured manually using a Nageotte chamber, along with flow cytometry methods and an ADAM-rWBC automated instrument (NanoEnTek, Seoul, South Korea). The efficiency was calculated by measuring the time required for the analysis of one specimen ten times consecutively.Flow cytometry and the ADAM-rWBC were able to detect four sporadic cases that had residual WBCs exceeding 1/μL that were not detected by the manual method. Analysis time was the shortest with the ADAM-rWBC, followed by flow cytometry and the manual method.Our data suggest that hospital blood banks require quality control of residual WBCs; among the methods evaluated in this study, the portable microscopic cell counter offers the best time efficiency.     

Vascular flow limitations affecting the cervico-cranial region: Understanding ischaemia

BackgroundBlood flow and brain ischaemia have been of interest to physical therapists for decades. Despite much debate, and multiple publications around risk assessment of the cervical spine, more work is required to achieve consensus on this vital, complex topic. In 2020, the International Federation of Orthopaedic Manipulative Physical Therapists (IFOMPT) Cervical Framework adopted the dubious terminology ‘vascular pathologies of the neck’, which is misleading, on the premise that 1) not all flow limitations leading to ischaemia, are associated with observable blood vessel pathology and 2) not all blood flow limitations leading to ischaemia, are in the anatomical region of the ‘neck'.ObjectiveThis paper draws upon the full body of haemodynamic knowledge and science, to describe the variety of arterial flow limitations affecting the cervico-cranial region.DiscussionIt is the authors’ contention that to apply clinical reasoning and appropriate risk assessment of the cervical spine, there is a requirement for clinicians to have a clear understanding of anatomy/anatomical relations, the haemodynamic science of vascular flow limitation, and related pathologies. This paper describes the wide range of presentations and haemodynamic mechanisms that clinicians may encounter in practice. In cases with a high index suspicion of vascular involvement or an adverse response to assessment/intervention, appropriate referral should be made for further investigations, using consistent terminology. The term ‘vascular flow limitation’ is proposed when considering the range of mechanisms at play. This fits the terminology used (in vascular literature) at other anatomical sites and is understood by medical colleagues.     

Crosstalk of the Heart and Periphery: Skeletal and Cardiac Muscle as Therapeutic Targets in Heart Failure

Heart failure syndrome is initiated as the body's metabolic needs temporarily exceed the pumping capacity of the heart. In most cases, this phenomenon tends to occur during physical exercise. Although not always subjectively recognized, limited exercise capacity remains the clinical hallmark of congestive heart failure. It can be measured objectively as reduced skeletal muscle performance and maximal whole-body oxygen uptake, which are not necessarily explained by central haemodynamic abnormalities. In fact, the initial cardiac condition sets forth a series of peripheral adaptations that are potentially life-saving during acute decompensation but become disadvantageous and symptom-generating in stable heart failure. Inodilator drugs were theoretically ideal to revert the adverse haemodynamic crosstalk between the heart and periphery. However, these drugs failed to improve prognosis in congestive heart failure, whereas drugs that did so showed typically unimpressive haemodynamic effects. Exercise therapy has recently emerged as a safe and effective way to enhance physical performance and subjective well-being in congestive heart failure. A dual therapeutic approach is suggested, consisting of exercise training to improve the periphery and the use of cardioprotective drugs to limit cardiac cellular damage from neurohormonal activation.     

Post-exercise cutaneous hyperaemia resulting from local exercise of an extremity

Large changes in skin blood flow occur after exercise. Most studies have concentrated on the systemic effects of vigorous exercise on skin blood flow. We were interested in the post-exercise response in the neighbourhood of focal exercise. We used a painless neuromuscular electronic stimulator to exercise the muscles of the forearm, producing flexion of the fingers. There was no change in blood pressure and only a small increase in heart rate during this exercise. We measured blood flow during a 5-min pre-exercise period and a 5-min post-exercise period at the forearm, at the dorsum of the index finger and on the pad of the index finger. We also measured values on the contralateral non-exercised extremity during exercise as well as during matched time periods in control experiments with no exercise. Exercise did elicit an increased blood flow in the post-exercise period at all three sites compared with the control experiments with no exercise and on the contralateral extremity. For example, the increase in blood flow at the finger dorsum was 2.1±0.1 ml (min 100 g)^?1 after exercise compared with ?0.08±0.09 ml min^?1 100 g^?1 during the control experiment and 0.1±0.1 ml (min 100 g)^?1 on the contralateral arm (all P<0.01). The local application of heat at the site of blood flow monitoring produced a substantial increase in the post-exercise response at the two finger locations [27.4±0.4 ml (min 100g)^?1 at the finger dorsum], but not at the arm. This is the first demonstration that highly focal exercise, unaccompanied by a systemic haemodynamic response, can elicit a post-exercise cutaneous hyperaemia. Local heating produced a large synergistic increase in the post-exercise hyperaemia at sites with arteriovenous microvascular perfusion but not at sites with primarily nutritive perfusion. These findings show that local vasoregulatory changes occur in response to exercise, even in the absence of whole-body haemodynamic and thermal change.     

Detection of lactate threshold by including haemodynamic and oxygen extraction data

To date, few attempts have been made to correlate cardiovascular variables to lactate threshold (L(T)). This study was designed to determine the relationship between the accumulation of blood lactate and several haemodynamic variables during exercise. Eight male volunteer cyclists performed an incremental test on an electromagnetically braked cycle-ergometer consisting of a 50 W linear increase in workload every 3 min up to exhaustion. Blood lactate was measured with a portable analyser during each exercise step. Oxygen consumption (VO(2)) and pulmonary ventilation were measured by means of a mass spectrometer while heart rate, stroke volume and cardiac output (CO) were assessed by impedance cardiography. The arterio-venous oxygen difference (A-V O(2) Diff) was obtained by dividing VO(2) by CO. By applying the D(max) mathematical method, L(T) and thresholds of ventilatory and haemodynamic parameters were calculated. The Bland and Altman statistics used to assess agreement between two methods of measurement were applied in order to evaluate the agreement between L(T) and thresholds derived from ventilatory and haemodynamic data. The main result was that most of the haemodynamic variables did not provide thresholds which could be used interchangeably with L(T). Only the threshold of A-V O(2) Diff showed mean values that were no different compared to L(T) together with limits of agreement that were not very wide between thresholds (below +/-25%). Hence of the haemodynamic parameters, A-V O(2) Diff appears to be the one most closely coupled with lactate accumulation and consequently it is also the most suitable for non-invasive calculation of the L(T).     

Doppler findings in the fetal and uteroplacental circulation: a promising guide to clinical decisions

The combination of real time and Doppler ultrasonic methods has opened up new possibilities for the study of fetal and uterine haemodynamics in humans particularly for the umbilical, uterine and fetal cerebral arteries. A pathological finding in blood velocity waveforms seems to be an early and consistent alteration which precedes other markers of chronic fetal distress. The challenges are to differentiate between fetal and uteroplacental aetiologies of chronic fetal asphyxia and to search for effective treatment of early fetal distress. Recent data on the practical value of haemodynamic studies in different perinatal complications is presented in this review.     

Central and peripheral haemodynamic effects of hyperglycaemia,hyperinsulinaemia, hyperlipidaemia or a mixed meal

The aim of the present study was to evaluate the haemodynamic changes during hyperinsulinaemia, hyperglycaemia or hypertriglyceridaemia in relation to those following a mixed meal. Ten subjects were subjected to hypertriglyceridaemia (3.9 mmol/l) for 2 h by an infusion of Intralipid and heparin. Nine subjects received a hyperglycaemic clamp (12.5 mmol/l) with octreotide and low-dose insulin infusion to maintain normoinsulinaemia (10 m-units/l). Ten subjects received saline for 2 h as a control and, thereafter, 2 h of normoglycaemic hyperinsulinaemic clamp (80 m-units/l). Finally, ten subjects were evaluated for 2 h following an ordinary mixed meal. Calf blood flow was measured by venous occlusion plethysmography and cardiac index by thoracic bioimpedance. Both the mixed meal and normoglycaemic hyperinsulinaemia lowered total peripheral resistance, and increased calf blood flow and cardiac index, whereas blood pressure decreased (P <0.05-0.001). Both hyperglycaemia and hypertriglyceridaemia increased calf blood flow, but blood pressure was unchanged. Total peripheral resistance was unchanged in hypertriglyceridaemia, whereas hyperglycaemia induced a significant increase. Normoglycaemic hyperinsulinaemia induced a haemodynamic pattern similar, but to a lesser extent, to the pattern seen following a mixed meal. Hyperinsulinaemia seems to be a major mediator of the haemodynamic response, but other factors are obviously also of great importance. Hypertriglyceridaemia and hyperglycaemia induced haemodynamic responses that are not similar to those seen following a mixed meal.     

Anaphylactic shock: the advantages of intra aortic balloon counter pulsation for the treatment of heart failure

The authors report a patient with a history of angina pectoris who developed anaphylactic shock that was complicated by a heart failure due to focal heart ischaemia. Early coronary angiography confirmed the diagnosis of localised coronary hypoperfusion. Intra aortic balloon counter pulsation succeeded in the restoration of coronary blood flow and haemodynamic stability. The authors discuss the opportunity of such treatment when a focal coronary hypoperfusion is diagnosed.     

Functional limitation in aortic valve disease: superiority of bicycle test to symptom-rated appraisal?

The overall functional capacity in aortic valve disease was evaluated using the New York Heart Association criteria and symptom-limited bicycle ergometry in 80 patients who underwent cardiac catheterization. The correlations between exercise performance and resting cardiac haemodynamics and clinical class were poor. Similar exercise tolerance appeared to be associated with comparable resting left ventricular (LV) performance in each haemodynamic subgroup. Limitation in exercise tolerance in aortic stenosis (n = 25), as defined by peak work-load achieved and work-pulse index, together with an inability to raise systolic blood pressure during exercise, appeared to be associated not only with a more significant reduction in LV systolic pump function and compliance but also with greater LV dilatation. A lack of correlation between exercise performance and resting LV function was seen in patients with aortic regurgitation (n = 35); and, to large extent, in those with combined lesion (n = 20). The severity of the valvular lesion was not indicated by functional limitation in any of the subgroups, although greater systolic blood pressure during exercise appeared to reflect more significant valvular leakage in the combined lesion group. It is concluded that objective tests of exercise tolerance are to be preferred in monitoring the course of the disease and the therapy provided. Aortic regurgitation appears to cause as great a limitation in exercise tolerance as does aortic stenosis alone, but may not be associated with greater deterioration in LV function at a similar level of functional limitation. Pressure overload to the LV may explain the ability of impaired LV function to reflect the limitation in exercise tolerance in cases of aortic stenosis.     

An automated reticulocyte counting method: preliminary observations

We evaluated the counting of reticulocytes in the peripheral blood with a newly developed flow cytometer type of automated counter that performs a single test within 60 s. The volume of sample needed is 100 microliters and the cells are stained with auramine-O in the counter. The mean within-run reproducibility was 4.66% (CV, n = 50), and dilution of blood gave highly linear results with an r value of 0.996. Correlation was good between manual reticulocyte counts and those performed with the counter (r = 0.893). Samples with large numbers of leucocytes, erythrocytes, or platelets did not interfere with the automated reticulocyte counting, and provided accurate and precise data.     

Endoleaks after endovascular repair of abdominal aortic aneurysm: value of CEUS

Endovascular repair (EVAR) is playing an increasingly role in the treatment of abdominal aortic aneurysm. A successful procedure depends on the complete sealing of the aneurysm sac from blood flow to achieve general pressure relief and avoid aneurysm rupture, with a shrinkage of the aneurysm sac. The most common complication of EVAR is endoleak that is the persistence of perigraft flow within the aneurysm sac, which has to be considered the major cause of enlargement and rupture of the aneurysm, and the main indication for surgical late conversion. For this reason, strict surveillance of these patients is mandatory for the early detection of endoleaks and the preferred method of follow-up is represented by CT angiography. However, CTA has limitations. The investigation is repeated several times, making radiation exposure a necessary concern. Therefore, it would be useful to have another reliable diagnostic examination during follow-up. Color duplex ultrasound is non-invasive, does not use radiation or contrast medium, is less expensive, easy to perform and widely available. However, this technique obtained poor results in terms of sensitivity in the detection of endoleaks. In the last years, the introduction of ultrasound contrast agents and contrast-specific imaging has, however, rekindled interest in this modality and its potential for replacing of CTA in routine surveillance. The purpose of this review is to highlight the diagnostic value of CEUS in the post-EVAR endoleaks detection.     

A systematic review of exercise interventions in patients with heart failure

The incidence of heart failure (HF) is increasing as the population ages. Pharmacotherapy is an important component of treatment and yields significant improvements in survival and quality of life. In recent decades, exercise has gradually become accepted as an intervention beneficial to patients with HF, but more information is needed to clarify the effects of exercise and optimize interventions. Therefore, a systematic review of randomized controlled trials published from 1966 to October 2006 was carried out via PubMed. About 69 trials were reviewed, which used as main outcome measures: (a) central hemodynamic parameters, (b) peripheral blood flow, (c) endothelial function, (d) activation of neurohormones and cytokine systems, (e) structure of and metabolism in skeletal muscles, and/or (f) quality of life. Study findings suggest that the favorable physiological responses to exercise might slow some of the pathophysiological progression of HF. However, most of the trials reviewed here were based on relatively small samples and selected participant groups, and the exercise programs varied widely. These limitations and inconsistencies need to be addressed through further studies. Furthermore, reliable strategies for maintaining the positive effects of exercise and extending them to patients' daily life and quality of life are scarce in these trials. These domains need further exploration through rationally designed, large-scale randomized controlled trials.     

Physiological and symptomatic responses to cycling and walking in intermittent claudication

To shed light on the potential efficacy of cycling as a testing modality in the treatment of intermittent claudication (IC), this study compared physiological and symptomatic responses to graded walking and cycling tests in claudicants. Sixteen subjects with peripheral arterial disease (resting ankle: brachial index (ABI) < 0.9) and IC completed a maximal graded treadmill walking (T) and cycle (C) test after three familiarization tests on each mode. During each test, symptoms, oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (RER) and heart rate (HR) were measured, and for 10 min after each test the brachial and ankle systolic pressures were recorded. All but one subject experienced calf pain as the primary limiting symptom during T; whereas the symptoms were more varied during C and included thigh pain, calf pain and dyspnoea. Although maximal exercise time was significantly longer on C than T (690 +/- 67 vs. 495 +/- 57 s), peak VO2, peak VE and peak heart rate during C and T were not different; whereas peak RER was higher during C. These responses during C and T were also positively correlated (P < 0.05) with each other, with the exception of RER. The postexercise systolic pressures were also not different between C and T. However, the peak decline in ankle pressures from resting values after C and T were not correlated with each other. These data demonstrate that cycling and walking induce a similar level of metabolic and cardiovascular strain, but that the primary limiting symptoms and haemodynamic response in an individual's extremity, measured after exercise, can differ substantially between these two modes.     

Lifetime change in central and peripheral haemodynamics in relation to exercise capacity

Exercise capacity as well as many resting central and peripheral haemodynamic features declines by age. We aimed to investigate which haemodynamic features change the most during life and which change in parallel to exercise capacity. We performed a maximal bicycle exercise test with gas exchange in 103 healthy subjects (24 young, 55 middle‐aged and 24 elderly). Endothelial function, arterial compliance/stiffness and heart rate variability (HRV) were evaluated, and the myocardium and carotid arteries were investigated by ultrasound. Exercise capacity declined by almost 50% over the lifespan. Several markers reflecting arterial compliance/stiffness and HRV, as well as carotid intima–media thickness (IMT), showed lifetime impairments by >100%, while markers of LV systolic function, diastolic blood pressure and carotid artery blood flow showed only minor changes with age. The decline in exercise capacity clusters closely with many other variables measured during the exercise test, but also to resting vital capacity, left ventricular end‐diastolic diameter and resting gas exchange (VO₂, VCO₂) to a lesser degree. Resting vital capacity was closely related to exercise capacity in the middle‐aged group. We conclude that many of the resting markers of central and peripheral haemodynamics declined during life, in parallel to the decline in exercise capacity. However, some haemodynamic features, such as LF/HF ratio at HRV, stiffness index beta of the carotid artery, and heart rate reserve at the exercise test, showed a more exaggerated decline, indicating that those are not closely linked to exercise capacity.