Introduction
Interstitial fluid pressure (Pif) is a key determinant in increasing the transcapillary driving pressure which pulls fluid from the microcirculation into the interstitial space at the onset of edema. PGE1 induces lowering of interstitial fluid pressure in rat skin and is also able to prevent fibroblast mediated collagen gel contraction (Berg et al., 1998). Rubin et al. (1999) showed that increased transcapillary transport of 51Cr-EDTA into the centre of a tumor measured by microdialysis was paralleled by the lowering of interstitial fluid pressure induced by PGE1.
Methods
Transcapillary transport was measured with a microdialysis pump (CMA Microdialysis, Sweden) and microdialysis probes (CMA 12 and CMA 20). The probes were inserted into the subcutaneous backskin and in the jugular vein of female rats anaesthetised with sodium pentobarbital (50 mg/kg i.p.). Cannulation of left jugular vein, right carotid artery and left femoral vein was performed for measurements of 51Cr-EDTA in plasma via plasmaprobe, MAP-registration and i.v. injections of 51Cr-EDTA, respectively. Two different protocols were used:
1. Subcutaneous administration of PGE1 (7,5, 15 and 75 mg) around the probe.
2. Administration of PGE1 (15 and 150 ”g) via the probe.
Control measurements were performed in the same animal via probe and administration of vehicle. Administration of the radiolabelled tracer and PGE1 was performed simultaneously. The fractional dialysate volumes were collected at the following time intervals: 5, 20, 15, 30, 45, 60, 75 and 90 min and the radioactivity in the dialysate volumes were determined in a gamma-counting system.
Calculations were performed by comparing the area under curve (AUC) for the plasma and microdialysis probe levels of 51Cr-EDTA and calculated for three time periods ('initial 10 min', 'middle 35 min' and 'last 45 min').
Results
AUC was significantly increased with enhanced transcapillary transport of 51Cr-EDTA for the subcutaneously administered PGE1 (15 ”g) at the 'middle 35 min' and the 'last 45 min' time periods (p=0,02 and p= 0,03, respectively).
The delayed effect observed in these groups is most likely due to the increased interstitial fluid volume around the probe induced by the injection of PGE1.
There was a significant spontaneous increase of AUC within the 'initial 10 min' in the groups with administration of PGE1 through the probe (p<0,03).
Conclusions
The present approach of using microdialysis for analysing the effects of PGE1 on lowered interstitial fluid pressure and transcapillary transport, demonstrates that PGE1 increases transcapillary transport of 51Cr-EDTA.
References
Berg, A., Ekwall, A.K.H., Rubin, K., Stjernschantz, J. & Reed, R.K. 1998. Am J Physiol 274, H663-H671
Rubin, K., Salvesen, G.S. & Reed, R.K. 2000. manuscript