Factors associated with hyperdynamic or hypodynamic circulation and role of platelet-activating factor in hemodynamic alterations in bacterial peritonitis in conscious rats.

Abstract

Male Wistar rats injected intraperitoneally (i.p.) with 10(9) U Escherichia coli ATCC 25922 developed acute bacterial peritonitis. Hemodynamic studies, with microspheres labeled with 103Ru 57Co, and 113Sn, were performed before, 30 min after bacterial injection, and 30 min after administration of either the platelet-activating factor (PAF) antagonist BN-52021 (5 mg/kg body weight) or isotonic saline. A blood sample of 0.3 ml was obtained for bacterial culture and endotoxemia measurements. Plasma PAF levels were measured in a different group of 10 control rats and 20 animals with experimental peritonitis. One group of rats injected with E. coli (n = 13) displayed hyperdynamic circulation, with an increase in cardiac output (CO) from 15.1 +/- 1.2 to 19.4 +/- 1.1 ml/min/100 g body weight and a decrease in total peripheral resistance (TPR) from 19.5 +/- 2.4 to 14.9 +/- 1.1 dynes.s.cm-5 10(-4). Furthermore, these rats showed high endotoxin blood concentrations and low hemoculture levels. The remaining 7 peritonitic rats showed a significant decrease in CO from 16.3 +/- 1.6 to 12.7 +/- 1.2 ml/min/100 g body weight and an increase in TPR from 17.3 +/- 1.8 to 22.6 +/- 2.8 dynes.s.cm-5 10(-4). In addition, these rats showed low endotoxin blood concentrations and high hemoculture levels. Endotoxin blood concentrations were positively correlated with the change in CO (r = 0.87, p < 0.05), and cell hemocultures were positively correlated with CO (r = 0.89, p < 0.05). Rats with high endotoxin blood levels showed higher PAF plasma levels than control rats or peritonitic rats with low endotoxin blood levels. When peritonitic rats were injected with the specific PAF-receptor blocker BN-52021 (5 mg/kg body weight) as a bolus, CO and TPR returned to baseline values in both groups of animals. These data suggest that the hemodynamic changes induced by bacterial peritonitis depend on endotoxemia and bacteremia in opposite ways. In addition, PAF appears to be involved in both the hyperdynamic and hypodynamic hemodynamic changes shown by peritonitic rats.