Computer simulation of arterial flow with applications to arterial and aortic stenoses.

Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity.

Severe elevation of red blood cell number is often associated with hypertension and thromboembolism resulting in severe cardiovascular complications. However, some individuals such as high altitude dwellers cope well with an increased hematocrit. We analyzed adaptive mechanisms to excessive erythrocytosis in our transgenic (tg) mice that due to hypoxia-independent erythropoietin (Epo) overexpression reached hematocrit values of 0.8 to 0.9 without alteration of blood pressure, heart rate or cardiac output. Extramedullar erythropoiesis occurred in the tg spleen leading to splenomegaly. Upon splenectomy, hematocrit in tg mice decreased from 0.89 to 0.62. Tg mice showed doubled reticulocyte counts and an increased mean corpuscular volume. In tg mice plasma volume was not elevated whereas blood volume was 25% of the body weight compared to 8% in wildtype (wt) siblings. While plasma viscosity did not differ between tg and wt, tg whole-blood viscosity increased to a lower degree (4-fold) than expected from corresponding hemoconcentrated wt blood (8-fold). This moderate increase in viscosity is explicable by the up to 3-fold higher elongation of tg erythrocytes at physiological shear rates. Apart from the nitric oxide mediated vasodilation we reported earlier, adaptation to high hematocrit in tg mice involves regulated elevation of blood viscosity by increasing erythrocyte flexibility. KEYWORD polycythemia, extramedullary erythropoiesis, splenomegaly, splenectomy, microcirculation For personal use only. by guest on June 3, 2013. bloodjournal.hematologylibrary.org From

Scientific Heading: RED CELLS Transgenic mice overexpressing erythropoietin adapt to excessive erythrocytosis by regulating blood viscosity

✓ Although blood velocity in the major intracranial vessels is readily measured with transcranial Doppler ultrasound (TCD), the interpretation of velocity changes is by no means straightforward. For example, a velocity increase can arise from either a local stenosis or a decrease in downstream resistance, and these mechanisms have contradictory implications for blood flow. To determine whether TCD pulsatility might distinguish these two mechanisms, Doppler ultrasonic readings were taken from an artificial vascular model under conditions of either stenosis or distal dilation. In addition, TCD studies of nine patients with unihemispheric arteriovenous malformations (AVM's) and 16 TCD studies of seven patients with unihemispheric aneurysmal vasospasm were reviewed, and pulsatilities of the AVM's (representing decreased resistance) were compared with those of the vasospastic vessels (representing stenosis). The average percentage drop in pulsatility in the vasodilated configuration of the model/percentage inc...

Transcranial Doppler pulsatility in vasodilation and stenosis

A variety of optical techniques have been developed over the years for experimental use in vascular disease, mainly for the assessment of lower limb peripheral arterial disease (PAD). Optical techniques have several advantages over more traditional experimental approaches. Photoplethysmograph (PPG) was one of the earliest methods used for this purpose; PPG satisfies many of the conditions for a non-invasive technique to estimate skin blood flow using infrared light, not only for research but also in clinical practice. PPG is a promising, safe and easy-to-use tool for diagnosis and early screening of various atherosclerotic pathologies and could be useful for regular GP-assessment or even self-monitoring of PAD at home or during individual physical exercises. This review discusses the application of PPG in the assessment of PAD.

Optical techniques in the assessment of peripheral arterial disease.

Pulsatile haemodynamics associated with graded degrees of experimentally produced stenosis were studied in the canine femoral artery. Invasively determined pulsatile blood flow and noninvasively determined blood velocity with Doppler ultrasound were measured an average of 1.3 and 2.3 cm proximal to the stenosis, respectively. Pulsatile blood pressure was measured 0.6 cm proximal and 3.7 cm distal to the stenosis. With increasing severity of stenosis there were progressive increases in the femoral artery hydraulic input impedance moduli and in the ratio of the impedance moduli to the zero harmonic impedance (or total resistance). This resulted in: a) a progressive reduction in the Fourier harmonic moduli and pulsewave amplitudes of flow, velocity, and distal pressure; b) a progressive increase in the fifth-seventh proximal pressure harmonic moduli; but c) little change in mean proximal pressure or its first 4 harmonic moduli. The data confirm the well known phenomena of a 'critical stenosis' in that there is little decrease in resting mean blood flow until there is a 70 to 80 stenosis (area reduction). Also the oscillatory portions of the femoral artery data were more sensitive to the changes in stenosis than were the nonoscillatory parameters, which confirms previously reported findings from the thoracic aorta. However, the femoral artery haemodynamics exhibited a greater amount of frequency dependent behaviour than the thoracic aorta which is probably the result of a more complex interaction of reflections from the stenosis and from the periphery in the femoral artery than in the thoracic aorta. The sensitive changes in oscillatory haemodynamics may provide a useful basis for noninvasive and invasive physiological assessment of human peripheral atherosclerotic stenosis and of experimental stenosis in animals.

Darwin W. Peterson

Papers

Noninvasively and invasively measured pulsatile haemodynamics with graded arterial stenosis.