"Artificial lymphatic system": a new approach to reduce interstitial hypertension and increase blood flow, pH and pO2 in solid tumors.
A mechanical drainage system, the "artificial lymphatic system" (ALS), consisting of a vacuum source and drain, is evaluated for its ability to aspirate the interstitial fluids responsible for the elevated interstitial fluid pressure (IFP) observed in solid tumors. IFP, pH, and pO2 radial profiles were measured before and after aspiration using wick-in-needle (WIN) probes, needle pH and oxygen electrodes, respectively. Laser Doppler flowmetry measured temporal changes in blood flow rate (BFR) at the tumor surface during aspiration. The WIN probe and IFP profile data were analyzed using numerical simulation and distributed mathematical models, respectively. The model parameter, P(E), reflecting central tumor IFP, was reduced from 15.3 to 5.7 mm Hg in neuroblastoma and from 13.3 to 12.1 mm Hg in Walker 256, respectively, following aspiration. The simulation demonstrated that spatial averaging inherent in WIN measurements reduced the calculated magnitude of the model parameter changes. IFP was significantly lower (p<0.05), especially in regions surrounding the drain, and BFR was significantly higher (p<0.05) following 25 and 45 min of aspiration, respectively; pH and pO2 profiles increased following aspiration. The experimental and mathematical findings suggest that ALS aspiration may be a viable way of reducing IFP and increasing BFR, pO2, and pH and should enhance solid tumor chemo and radiation therapy.
Memorial Sloan Kettering Cancer Center's Department of Surgery/Orthopaedic Service, Memorial Sloan Kettering Cancer Center, New York, NY 10021, USA. direstag@mskcc.org
G R
GR
DiResta
J
J
Lee
J H
JH
Healey
A
A
Levchenko
S M
SM
Larson
E
E
Arbit
D000818:Animals; D001187:Artificial Organs; D001698:Biomedical Engineering / Q000295:instrumentation; D001783:Blood Flow Velocity; D005110:Extracellular Space / Q000502:physiology; D006863:Hydrogen-Ion Concentration; D008196:Lymph / Q000502:physiology; D008208:Lymphatic System; D008297:Male; D009374:Neoplasms, Experimental / Q000098:blood supply / Q000503:physiopathology / Q000628:therapy*; D010100:Oxygen / Q000378:metabolism; D011312:Pressure; D051381:Rats; D011923:Rats, Nude; D017207:Rats, Sprague-Dawley
D010100:Oxygen