Infrared imaging of nitric oxide-mediated blood flow in human sickle cell disease.
Vascular dysfunction is an important pathophysiologic manifestation of sickle cell disease (SCD), a condition that increases risk of pulmonary hypertension and stroke. We hypothesized that infrared (IR) imaging would detect changes in cutaneous bloodflow reflective of vascular function. We performed IR imaging and conventional strain gauge plethysmography in twenty-five adults with SCD at baseline and during intra-arterial infusions of an endothelium-dependent vasodilator acetylcholine (ACh), an endothelium-independent vasodilator sodium nitroprusside (SNP), and a NOS inhibitor L-NMMA. Skin temperature measured by IR imaging increased in a dose-dependent manner to graded infusions of ACh (+1.1°C, p<0.0001) and SNP (+0.9°C, p<0.0001), and correlated with dose-dependent increases in forearm blood flow (ACh: +19.9 mL/min/100 mL, p<0.0001; r(s)=0.57, p=0.003; SNP: +8.6 mL/min/100 mL, p<0.0001; r=0.70, p=0.0002). Although IR measurement of skin temperature accurately reflected agonist-induced increases in blood flow, it was less sensitive to decreases in blood flow caused by NOS inhibition. Baseline forearm skin temperature measured by IR imaging correlated significantly with baseline forearm blood flow (31.8±0.2°C, 6.0±0.4 mL/min/100 mL; r=0.58, p=0.003), and appeared to represent a novel biomarker of vascular function. It predicted a blunted blood flow response to SNP (r=-0.61, p=0.002), and was independently associated with a marker of pulmonary artery pressure, as well as hemoglobin level, diastolic blood pressure, homocysteine, and cholesterol (R(2)=0.84, p<0.0001 for the model). IR imaging of agonist-stimulated cutaneous blood flow represents a less cumbersome alternative to plethysmography methodology. Measurement of baseline skin temperature by IR imaging may be a useful new marker of vascular risk in adults with SCD.
Infrared Imaging and Thermometry Unit, National Institute of Biomedical Imaging and Bioengineering, National Institutes of Health, MD, USA.
Alexander M
AM
Gorbach
Hans C
HC
Ackerman
Wei-Min
WM
Liu
Joseph M
JM
Meyer
Patricia L
PL
Littel
Catherine
C
Seamon
Eleni
E
Footman
Amy
A
Chi
Suzana
S
Zorca
Megan L
ML
Krajewski
Michael J
MJ
Cuttica
Roberto F
RF
Machado
Richard O
RO
Cannon
Gregory J
GJ
Kato
D000109:Acetylcholine / Q000378:metabolism; D000328:Adult; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000473:pathology*; D001783:Blood Flow Velocity; D004305:Dose-Response Relationship, Drug; D004452:Echocardiography / Q000379:methods; D004730:Endothelium, Vascular / Q000473:pathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D012044:Regression Analysis; D012306:Risk; D012881:Skin Temperature; D013055:Spectrophotometry, Infrared / Q000379:methods*; D019323:omega-N-Methylarginine / Q000494:pharmacology
D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine