Current Research Approaches:

Human Thermoregulation and Microvascular Research Laboratories

Intradermal Microdialysis (MD) is a safe and effective method to locally deliver pharmacological agents directly to the cutaneous vasculature. Drugs delivered using microdialysis do not affect the systemic circulation.  Also, this technique enables exploration of the fluid-composition surrounding tissues.  During the procedure we implant in the skin a thin tube of semi-permeable membrane (“catheter”) that mimics a capillary blood vessel (Figure 1). As a physiological saline perfuses the membrane, there is bi-directional exchange of molecules between the perfusing saline and fluid bathing the surrounding tissue.  Currently, our studies employ microdialysis to explore mechanisms underlying impairedcontrol of skin blood flow under conditions such as disease (e.g. hypercholesterolemia, hypertension) or drug-therapy (e.g. low-dose aspirin, statins).

Laser Doppler Flowmetry (Figure 1) non-invasively provides a qualitative measure of skin blood flow to a depth of about 1 mm in the skin using a weak laser light.  The flowmeter continuously measures skin blood flow using a fiber optic probe.  Combined with (MD), it

Figure 1.  Intradermal Microdialysis and Laser Doppler Flowmetry techniques.

provides a powerful tool to evaluate the

mechanisms controlling of skin blood flow.

 

CutaneousBiopsy samples (3mm diameter)are obtained using sterile technique (Figure 2).  The subcutaneous and intradermal layers containing the greatest density of blood vessels are homogenized and analyzed.  The analyses provide information on the local mechanisms governing the control of skin blood flow.  Among the analysis performed are reverse transcriptase-polymerase chain reaction (PCR) to determine mRNA expression of arginase I, II and eNOS; quantitative PCR to determine the relative expression of arginase I, II, and eNOS; arginase and eNOS activity assays; and western blot analysis to determine absolute protein concentration.

 

Passive Whole Body Heating and Cooling allows us to raise and lower body temperature while studying the physiological responses (e.g. cardiovascular, sweating, skin blood flow, etc.) and their mechanisms.  To accomplish this, we control the temperature of water flowing through tubing lining a special tube-suit (Figure 3) using precise heating/cooling circulators.

 

(Figure 3)
Demonstrating the tube-suite
 

 

 

Speckle Contrast Imager (moorFLPI) allows the production color-coded video of the real-time dynamics of blood flow in an area of skin in response to manipulations such as whole body heating/cooling, intradermal microdialysis, or under conditions of aging, disease, etc.  The movement of blood cells through vessels in the skin creates a random speckle-pattern when laser light illuminates skin.  The FLPI uses pattern-differences as a measure of blood flow.  The data produced by the imager (Figure 4) can be analyzed to assess differences in regional blood flow, dynamics of flow, distribution of flow, etc.

 

(Figure 4)
FLPI-Images of a hand showing recovery from reactive hyperemia induced by 5-minute occlusion of the arm. Greens, yellows, reds: more blood flow. Blues and purples: less blood flow.

 

 

Two Environmental Chambersare specialized laboratory facilities that enable the precise control of temperature and humidity for imposing a variety of defined environmental conditions during experiments.  The large-capacity chambers allow for experiments exploring human thermoregulatory responses to induced heat and cold stresses under resting and exercise conditions (Figure 5). 

Figure 5.  Exercise protocol in the environmental chamber.

Theenvironmental chambers provide for basic and applied human thermal physiology studies as well as research examining the performance of equipment and clothing, effectiveness of hydration strategies, etc.  Each is approximately 360 sq. ft. with an operational range of 5-60oC and relative humidity range of 10-95%.  Instrumentation and controls operate in either a manual or programmable mode.  The environmental chambers utilize a 3-mode controller (proportional, integral and derivative) to optimize stability and response.  Air is vertically discharged in an even pattern through the ceiling and returned through base molding on three sides.  The ceiling has been mapped for optimal laminar flow.