Improving contact area between the peritoneum and intraperitoneal therapeutic solutions.
A general assumption in peritoneal dialysis or intraperitoneal chemotherapy has been that a volume of 2 to 3 L in the human is sufficient to make contact with the entire anatomic peritoneum. On the basis of our previous experimental work and that of others, it was hypothesized that only a fraction of the anatomic peritoneum was in contact with the therapeutic solution in the cavity over a short period of time. It was also hypothesized that use of agitation of the experimental animal or a surfactant in the dialysis fluid would increase the contact area of the intraperitoneal solution. These hypotheses were tested by developing a method to measure the peritoneal contact area simultaneously with the anatomic peritoneal area. Anesthetized mice (25 to 35 g) received an injection of a relatively large volume (10 ml) of isotonic solution containing a radiolabeled protein that adhered to the peritoneum with which it came in contact. After a dwell of 1 to 24 h, the animal was killed and frozen. Cross sections of the abdominal and pelvic cavities were cut and placed against film to develop into autoradiograms, which represent the linear dimension of fluid contact in each sampling plane. The tissue sections that corresponded to the autoradiograms were stained to display the linear dimension of the anatomic peritoneum in the sampling plane. By imaging both the autoradiogram and the corresponding histologic slide, an estimate of the ratio of the contact area to anatomic area in each plane can be calculated (R(mean) = average of all ratios). Applying this method to mice that were dialyzed with an isotonic salt solution under quiescent conditions for 1 h produced R(mean) = 0.43 +/- 0.03. With rapid shaking of the animal, R(mean) = 0.54 +/- 0.03 (P: < 0.05). Addition of the surfactant dioctyl sodium sulfosuccinate (DSS) 0.5% to the solution under quiescent conditions increased R(mean) to 1.07 +/- 0.03 (P: < 0.001). Lengthening the dwell of the isotonic solution to 24 h increased R(mean) to >0.90. In further study of the effect of the concentration of DSS on contact area, there was a direct correlation of R(mean) with concentrations ranging from 0.0005 to 0.05% DSS. It is concluded that less than half of the mouse peritoneum is in contact with a large volume of solution in the peritoneal cavity. Maneuvers such as agitation and use of surfactant in the intraperitoneal solution increase the fraction of contact area. Also demonstrated was a direct dose-response of contact area versus intraperitoneal concentration of DSS, which may be useful in intraperitoneal therapies of peritoneal dialysis or intraperitoneal chemotherapy.
Nephrology Unit, University of Rochester Medical School, Rochester, New York.
Michael F
MF
Flessner
Nephrology Unit, University of Rochester Medical School, Rochester, New York.
Joanne
J
Lofthouse
Nephrology Unit, University of Rochester Medical School, Rochester, New York.
El Rasheid
ER
Zakaria
D000818:Animals; D001345:Autoradiography; D001639:Bicarbonates / Q000493:pharmacokinetics; D004338:Drug Combinations; D005936:Glucans / Q000493:pharmacokinetics; D005947:Glucose / Q000493:pharmacokinetics; D000077607:Icodextrin; D007274:Injections, Intraperitoneal; D007552:Isotonic Solutions / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D010537:Peritoneum / Q000378:metabolism*; D013997:Time Factors
D001639:Bicarbonates; D004338:Drug Combinations; D005936:Glucans; D007552:Isotonic Solutions; C051865:Krebs-Ringer solution; D000077607:Icodextrin; D005947:Glucose