STUDIO IFN - Ev-K2-CNR

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1 . 2 The splanchnic and renal flow assessment at high-altitude
with portable Doppler ultrasound.
Dipartimento di Medicina Clinica e Sperimentale – Università degli Studi di Padova.
Principal investigator: Dott. F. Noventa
Involved researchers: Dr. V. Pastega, Dr. D. Sacerdoti
Introduction
High-altitude (HA) hypoxia can lead to vasoconstriction or vasodilatation changes of
blood flow in human body vascular territories: this effect is well-know in pulmonary and
cerebral flow. But there are few studies about splanchnic and renal flow changes.
Doppler Ultrasound provides a simple, reproducible and not invasive assessment of
blood flow and vessels resistances and actually we can use new portable instruments
right for difficult situations like HA.
1.1 SPLANCHNIC FLOW
In the clinical practice abdominal vessels, in particular portal vein and splanchnic
arteries (mesenteric superior, hepatic, renal and splenic arteries) are studied by DU.
We can hypothesize a direct vasoconstriction effect of hypoxia on splanchnic
circulation, like pulmonary circulation and a hyperdinamic-hypercinetic syndrome like
cirrhosis, in portal circulation, especially on people that develops HA oedema.
In the hyperdinamic-hypercinetic syndrome are known 2 factors:
1) a splanchnic hyper inflow, due to decreased urine output
and increased fluid
balance, secondary to increase of renin activity and plasma aldosterone and to
vasodilatation by nitric oxide et al.
2) a difficult splanchnic outflow due to increase of hepatic resistances by catecholamine
et al.
These mediators are well-known on high-altitude pathology.
On the 1970 the first studies of splanchnic flow at high altitude measured portal flow
by galactose blood clearance.
Most recently it’s hypotized that hypoxia causes a largest sensitivity of vessels at
catecholamine, nitric oxide, carbon monoxide, that are found implicated in hypoxia. But
there are only studies in experimental conditions, not measures by ultrasonography.
In particular, we don’t know if there are differences between acclimatized subjects whit
and without “splanchnic disease” (anorexia, lack of appetite, lost bodyweight and
gastric symptoms).
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1.2 RENAL FLOW
The renal flow is indirectly studied by glomerular and tubular function measurements
and by renal and endocrine function.
A study of Australian Bicentennial Mount Everest Expedition in 1989 demonstrated in all
ten subjects during the first week at 5400 m: atrial natriuretic peptide level significantly
elevated 24 hour urine volume and urine sodium increased markedly, plasma renin
activity and plasma aldosterone levels decreased significantly.
Also successive studies demonstrates that glomerular and tubular function were only
slightly changed in spite of marked depression of the renin-aldosteron system and
increased plasma levels of norepinephrine. However renal vascular tone may increase
secondary to the increase of adrenosympathetic activity.
A 1992 study at 4350 m demonstrated the same about renin and aldosterone levels and
increased plasma norepinephrine, but the antidiuretic and antinatriuretic effects of
exercise were maintained in hypoxia and both environments seemed to be consequence
of decreased proximal tubular outflow.
These results seem demonstrate that renal glomerular and tubular function is well
preserved in acute hypoxia despite hormonal changed, suggesting that effects of acute
hypoxiaemia on renal haemodynamics are minor comparated with effects on cerebral
and coronary circulation. This might be the result of an appropriate resetting of
autoregolatory mechanism that would maintain the role of the kidney as a major sense
organ to hypoxiaemia and subsequently as a mediator of plasma volume regulation and
erythropoietin synthesis.
However in subjects whit Acute Mountain Sickness the severity of illness seem correlate
with a decreased urine output, increased fluid balance and decreased excretion of
sodium and potassium, produced in part by a decrease in glomerular filtration rate.
We believe that may be interesting to measure directly renal flow and variations about
vasodilatation or vasoconstriction in hypoxia.
1.3 DOPPLER ULTRASOUND
Duplex Doppler Ultrasound allows non-invasive evaluation of splanchnic and intrarenal
arterial blood flow and resistances.
In portal vein we can measure portal flow direction and velocity (PFV), and portal
diameter, related to portal hypertension.
In splanchnic vessels the following measurement can be made: peak systolic velocity
(PSV), end diastolic velocity (EDV) and mean velocity of superior mesenteric artery,
hepatic artery, splenic artery and renal artery and we can calculate pulsatility index
(PI=PSV-EDV/mean velocity) and resistive index (RI=PSV-EDV/PSV), correlated whit
arterial resistances.
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In renal vessels we can measure also acceleration index and acceleration time that
correlate whit intrarenal arterial resistances.
The applications of splanchnic and renal flow assessment in the clinical practice now
are for example: hemodynamic changes in cirrhosis, transplant renal and hepatic
stenosis, suspected angina abdominis, renal diseases and studies of physiology about
the effects of exercise, meal, drugs, hypotension, etc.
2. OBJECTIVE
The purpose of this work is to examine a group of 6-10 healthy subjects in HA to see if
acute and chronic HA hypoxia induce renal and splanchnic blood flow variations.
The study will examine also if there are differences between acclimatized subjects with
and without “splanchnic diseases” (anorexia, lack of appetite, lost bodyweight and
gastric symptoms).
3. DESIGN
A group of 6-10 healthy subjects will receive at sea level, HA (5500 m), after
acclimatation at HA and after came back to sea level:
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A ultrasound assessment with following measurement: portal flow velocity and
direction and portal diameter; peak systolic velocity (PSV), end diastolic velocity
(EDV), mean velocity, pulsatility index (PI=PSV-EDV/mean velocity) and resistive
index (RI=PSV-EDV/PSV) of superior mesenteric artery, hepatic artery, splenic artery
and renal artery; acceleration index and acceleration time of renal artery;
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A questionnaire about state of health;
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A measurement of body weight.
The number of should be 6-10 and they have to be fasting and at rest for the
ultrasonography assessment.
We will need 30 minutes for every assessment.
The analysis of results will include the ANCOVA analysis whit the graphics for the
continuous variables and Fisher Exact Test for the categorical variables.
4. WORK PROGRAMME
The work programme involves 4 phases:
PHASE 1
An ultrasound assessment and measurement of body weight at sea level in Italy on
every subject, before the departure.
PHASE 2
An ultrasound assessment, a questionnaire about state of health and the measurement
of body weight on every subject, when they reach the Pyramid (about 6 hour after the
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arrival or in the following days, because they have to be fasting and at rest) and after
15-20 days of acclimatization in the same situation.
PHASE 3
The same measurement of phase 1 at the sea level, when they came back in Italy.
PHASE 4
Analysis of results and their publications.
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