Peripheral Vascular Properties Measured by Strain Gauge Plethysmography (SPG)

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Blood Flow, Venous Pressure, Capacitance Relation and Microvascular Filtration Method  using Venous Occlusion, Mercury-in-silastic, strain gauge plethysmography

Limb blood flow, vascular resistance.  Mercury in silastic strain gauge venous occlusion phlethysmography and congestion cuffs are employed to obtain arterial flow in units of ml flow/100ml tissue. Cuffs are rapidly inflated to 45 mmHg recording the initial slope of change in circumference vs time. We increased occlusion pressure gradually until limb volume change was just detected. This is the venous pressure ( Pv ). Pressures less than Pv do not increase limb size. Estimated peripheral resistance [= (mean arterial pressure-Pv)/(indexed flow)].
To determine limb capacitance the limb was raised above heart level until no further decrease in volume occurred. Then we used 10 mmHg pressure steps, starting at the first multiple of 10 exceeding Pv, to a maximum of 60 mmHg. The venous pressure distal to congestion approximates the cuff pressure. Pressure was maintained for 4 minutes to reach a steady state. At lower pressures limb size reached a plateau shown in the figure.  At higher pressure steps, a plateau was not reached but after initial curvilinear venous filling, the limb increased linearly in size with time. The linear increase represents microvascular filtration. Above a critical pressure typically greater than Pv, denoted Pi, the lymphatic system cannot compensate for filtration and the interstitium enlarges at a rate proportionate to imposed pressure. Pressure steps between Pv and Pi result in a plateau, while pressure steps above Pi result in a curve asymptotic to a straight line with positive slope. We used least squares techniques to fit a straight line to the many points comprising the linear microvascular filtration contribution to filling. The linear portion was then electronically subtracted from the total curve to obtain a residual curve that reaches a plateau representing filling of capacitance vessels.
The Volume-Pressure Capacitance relation was calculated from the sum of residual portions shown as “intravascular filling” to which was added the estimate of supine venous volume obtained from limb raising .

The microvascular filtration relation (filtration rate versus pressure) was constructed for each subject. Normalized volume is expressed in units of (ml volume change/100ml tissue), normalized filtration rate is expressed in units of (ml/100ml tissue/min) and normalized filtration coefficient, Κf, the slope in the linear relation,  is expressed in units of (ml/100 ml tissue/min/mmHg). The intercept with the pressure axis of the flow-pressure graph is Pi which approximates the net oncotic pressure gradient for microvascular filtration and defines the threshold for edema formation. The extrapolated flow at zero hydraulic pressure approximates lymphatic flow.

Local Vascular Properties 

Local 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.

Isolated 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 (211) . Blood flow decreases if the reflexes are intact (94) . The limb then recovers in the supine position.

Large 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. 

Reactive 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 (212) while the duration is flow-mediated and related to NO, EDHF, adenosine and prostaglandins (213-217) . We will inflate a cuff to 30 mmHg above the systolic BP for 5 minutes to evoke a maximum response (218) . Upon cuff deflation , a second occlusion cuff is allowed to rapidly inflate to measure limb blood flow every 15 seconds (219) .  We will also assess the reactive hyperemic response of the skin using LDF measurements and repeated occlusions.




Peripheral Vascular Properties Measured by Strain Gauge Plethysmography (SPG)
Laser Doppler Flowmetry (LDF)
Indicator Techniques to Measure Blood Volume and Cardiac Output
Heart Rate and Blood Pressure
Near Infrared Spectroscopy
Microneurography and Muscle Sympathetic Nerve Activity (MSNA)
Transcranial Doppler Ultrasound (TCD)
Impedance Plethysmography (IPG)
Skeletal Muscle Pump