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The mechanisms underlying cytoplasmic pH (pHi) regulation in elicited rat peritoneal macrophages were investigated by electronic sizing and fluorescence determinations. Acid-loaded cells rapidly regained normal pH, by means of an amiloride-sensitive Na+/H+ exchange. When stimulated by 12-0-tetradecanoyl phorbol 13-acetate, macrophages displayed a biphasic pH, change: a marginal acidification followed by an alkalinization. The latter results from activation of Na+/H+ exchange, since it is Na+-dependent and prevented by amiloride. When the antiport is inhibited, the full magnitude of the initial acidification can be appreciated. This acidification is independent of the nature of the ionic composition of the medium and probably reflects accumulation of protons generated during the metabolic burst. Under physiological conditions, these protons are rapidly extruded by the Na+/H+ antiport. cytoplasmic pH; Na+/H+ exchange; Phorbol ester; Macrophage; (Rat)

Summary. The synergic relationship between Escherichia coli and Bacteroides fragilis was examined in a model of intra-abdominal abscess formation. The addition of B. fragilis to E. coli in the fibrin clot inoculum increased abscess weight and residual numbers of E. coli in the abscess at 7 days. In a reciprocal fashion, E. coli was capable of enhancing B. fragilis persistence in abscesses. Neither heat-killed E. coli nor heatkilled B. fragilis was able to mimic the synergic effect of its live counterpart. Furthermore, B. fragilis culture filtrate was unable to reproduce the ability of live B. fragilis to act synergically with E. coli. For B. fragilis to act synergically with E. coli, it had to be inoculated locally with E. coli in the peritoneal cavity, indicating that an effect on systemic resistance by B. fragilis was an unlikely mechanism for the production of bacterial synergy. These studies suggest that the synergic relationship between bacteria in polymicrobial infections is a complex one, resulting from intimate interactions between bacteria and the host in the local milieu of the infection.

Fibrin deposition in response to bacterial peritonitis appears to predispose to residual infection in the peritoneal cavity. Our previous studies have demonstrated that intraperitoneal fibrinolysis using human recombinant tissue plasminogen activator (t-PA) prevented abscess formation in a rat intra-abdominal sepsis model. To investigate the potential adverse side effects of its use in the peritoneal cavity, the effect of t-PA on colonic anastomotic wound healing and on systemic coagulation parameters was examined in the rat. T-PA did not adversely affect colonic healing five and ten days after anastomosis. In animals infected intraperitoneally at the time of the anastomosis, t-PA reversed the inhibition of healing induced by perianastomotic abscesses at five days. This effect was mediated by the ability of t-PA to prevent perianastomotic abscess formation. After intraperitoneal administration, t-PA had no effect on prothrombin and partial thromboplastin times in either uninfected or infected animals and there was no evidence of clinical bleeding related to its use. These studies suggest that intraperitoneal fibrinolysis using t-PA may provide a safe, effective form of adjuvant therapy in the management of fibrinopurulent peritonitis.