Monitoring of intragraft pressure of rejecting organs: increased tissue pressure can be reduced by hyaluronidase therapy.
BACKGROUND
The present study was undertaken in order to: (a) develop a new technique for measurement of interstitial pressure, (b) study the intragraft pressure of rejecting and non-rejecting organs, and (c) study the effect of treatment with the hyaluronan-degrading enzyme hyaluronidase on intragraft pressure. Treatment with hyaluronidase has previously been demonstrated to result not only in reduction of tissue hyaluronan but also in ameliorated interstitial edema, and we suggested that the diminished edema would lead to a reduced interstitial pressure as well.


METHODS
At day 5 after syngeneic or allogeneic rat heterotopic heart transplantation, the interstitial pressure of the cardiac grafts was measured using a microtip pressure sensor. Subsequently, the allogeneically grafted animals received a continuous intravenous infusion of either hyaluronidase (total dose: 60,000 U/kg) or vehicle during 2 hr; meanwhile, the interstitial pressure was monitored.


RESULTS
The intragraft pressure measurement technique was found to give reproducible results. The interstitial pressure of the rejecting (allogeneic) grafts was considerably higher than that of the non-rejecting (syngeneic), i.e., 12.3+/-1.6 mmHg vs. 1.1+/-0.6 mmHg (P<0.001). Hyaluronidase infusion effectively reduced the interstitial pressure as compared with vehicle treatment. By 20 min, the pressure had been reduced by 28% (P<0.01 compared with vehicle treatment); after 1 hr, by 49% (P<0.001); and after 2 hr, by 68% (P<0.01).


CONCLUSIONS
By using modern technology for tissue pressure measurements, we found that the strongly increased interstitial pressure of rejecting organs can be instantly reduced by intravenous administration of the hyaluronan-degrading enzyme hyaluronidase.
Johnsson
C
C
Department of Transplantation Surgery, University Hospital, Uppsala, Sweden. cecilia.johnsson@kirurgi.uu.se
Tufveson
G
G
Hällgren
R
R
D000818:Animals; D005110:Extracellular Space / Q000502:physiology*; D006084:Graft Rejection / Q000503:physiopathology*; D016027:Heart Transplantation / Q000276:immunology; D006651:Histocytochemistry; D006820:Hyaluronic Acid / Q000032:analysis; D006821:Hyaluronoglucosaminidase / Q000008:administration & dosage / Q000627:therapeutic use; D007275:Injections, Intravenous; D008297:Male; D008991:Monitoring, Physiologic / Q000379:methods*; D009997:Osmotic Pressure / Q000187:drug effects; D051381:Rats; D011921:Rats, Inbred WKY
D006820:Hyaluronic Acid; D006821:Hyaluronoglucosaminidase