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 intragra ft pressure of rejecting and non-rejecting organs, and (c) study the effect of treatment with the hyaluronan-degrading enzyme hyaluronidase on intragr aft pressure. Treatment with hyaluronidase has previously been demonstrated to result not only in reduction of tissue hyaluronan but also in ameliorat ed interstitial edema, and we suggested that the diminished edema would lea d to a reduced interstitial pressure as well. Methods, At day 5 after syngeneic or allogeneic rat heterotopic heart trans plantation, the interstitial pressure of the cardiac grafts was measured us ing a microtip pressure sensor. Subsequently, the allogeneically grafted an imals received a continuous intravenous infusion of either hyaluronidase (t otal 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 re producible 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 in fusion effectively reduced the interstitial pressure as compared with vehic le treatment, By 20 min, the pressure had been reduced by 28% (P < 0.01 com pared 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, w e found that the strongly increased interstitial pressure of rejecting orga ns can be instantly reduced by intravenous administration of the hyaluronan -degrading enzyme hyaluronidase.