Vascular properties can be assessed using strain gauge measurements. These are
useful in examining locally mediated responses such as the myogenic response
and the venoarteriolar reflex as well as more complex changes evoked, say, by
reactive hyperemia. By this means we expect to determine methods to assess
local endothelial dependent function.
limb dependency - activation of myogenic and venoarteriolar reflexes:
During screening exams and Specific Aim 4 we will hang the leg over the table
by approximately 35cm for 4 minutes while the patient remains otherwise supine
while SPG, IPG and LDF flow measurements are continue. Arterial BP and Pv
are increased by approximately 30 mmHg and activate myogenic (arterial BP) and
venoarteriolar (Pv) reflexes
. Blood flow decreases if the reflexes are intact
. The limb then recovers in the supine position.
Venous Pressure Step – activation of the venoarteriolar reflex: A
double cuff arrangement is used as explained in the preliminary experiments.
The inner congestion cuff is rapidly inflated to 45 mmHg and remains at
pressure for 4 minutes activating the venoarteriolar reflex while the patient
remains supine. At steady state limb flow measurements are repeated using the
outer cuff pressurized intermittently to 65 mmHg.
Hyperemia: The mechanisms of reactive hyperemia remain controversial. While there
is evidence for metabolic factors involving the local release of metabolites
and autacoids (e.g. adenosine, lactate, CO2, bradykinin, H+)
during ischemia, there is growing evidence that peak hyperemia is related to
the myogenic response
while the duration is
flow-mediated and related to NO, EDHF, adenosine and prostaglandins
. We will inflate a cuff
to 30 mmHg above the systolic BP for 5 minutes to evoke a maximum response
. Upon cuff deflation ,
a second occlusion cuff is allowed to rapidly inflate to measure limb blood
flow every 15 seconds
We will also assess the reactive hyperemic response of the skin using
LDF measurements and repeated occlusions.