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Factors associated with hyperdynamic or hypodynamic circulation and role of platelet-activating factor in hemodynamic
1Instituto Reina Sofia de Investigaciones Nefrológicas, Departamento de Fisiología y Farmacología, Universidad de Salamanca, Spain.
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.
Insights
Bacterial peritonitis in rats causes distinct hemodynamic changes, with endotoxemia linked to hyperdynamic circulation and bacteremia to hypodynamic states. Platelet-activating factor (PAF) plays a role in both responses.
Area of Science:
- Physiology
- Microbiology
- Pharmacology
Background:
- Acute bacterial peritonitis is a serious condition with complex hemodynamic alterations.
- The roles of endotoxemia and bacteremia in modulating these hemodynamic changes are not fully understood.
- Platelet-activating factor (PAF) is implicated in inflammatory responses, but its specific contribution to peritonitis-induced hemodynamics requires clarification.
Purpose of the Study:
- To investigate the differential effects of endotoxemia and bacteremia on hemodynamic parameters during acute bacterial peritonitis.
- To determine the involvement of platelet-activating factor (PAF) in mediating hemodynamic changes in this model.
- To assess the efficacy of a PAF antagonist in reversing peritonitis-induced hemodynamic alterations.
Main Methods:
- Male Wistar rats were induced with acute bacterial peritonitis using Escherichia coli.
- Hemodynamic parameters, including cardiac output (CO) and total peripheral resistance (TPR), were measured using radiolabeled microspheres.
- Blood samples were analyzed for endotoxin and bacterial levels, and plasma PAF concentrations were measured. A PAF antagonist (BN-52021) was administered to assess its effects.
Main Results:
- Two distinct hemodynamic profiles were observed: hyperdynamic circulation (increased CO, decreased TPR) associated with high endotoxin and low bacteria, and hypodynamic circulation (decreased CO, increased TPR) with low endotoxin and high bacteria.
- Endotoxemia positively correlated with increased CO, while bacteremia correlated with CO.
- Plasma PAF levels were elevated in rats with high endotoxin levels. Administration of the PAF antagonist BN-52021 normalized CO and TPR in both hyperdynamic and hypodynamic states.
Conclusions:
- Hemodynamic changes in bacterial peritonitis are differentially influenced by endotoxemia and bacteremia.
- Endotoxemia promotes a hyperdynamic state, whereas bacteremia is associated with a hypodynamic state.
- Platelet-activating factor (PAF) is a key mediator involved in both hyperdynamic and hypodynamic hemodynamic responses observed in experimental peritonitis.