Role of platelet-activating factor in hemodynamic derangements in an acute rodent pancreatic model.
Systemic hemodynamics were assessed in a model of experimental pancreatitis induced in rats by the retrograde injection of sodium deoxycholate, 40%, 1 mL/kg, in the pancreatic duct, using the radioactive microsphere technique before and 25 minutes after pancreatitis induction while blood pressure was stable (n = 10). A 55% decrease in cardiac out-put, a 14% decrease in heart rate, and a 3.3-fold increase in total peripheral resistances, without significant changes in blood pressure, were observed. Renal blood flow decreased by 68%. When rats were given BN-52021, a blocker of platelet-activating factor receptors (5 mg/h, IV; n = 13) coinciding with pancreatitis induction, no significant hemodynamic changes were observed. Animals treated with BN-52021 survived 89 +/- 10 minutes, whereas death occurred 67 +/- 5 minutes after pancreatitis induction in untreated rats (P less than 0.001). A different group of rats with pancreatitis showed higher blood levels of platelet-activating factor (0.28 +/- 0.06 ng/mL; n = 11) than control rats (0.16 +/- 0.03; n = 15; P less than 0.05). Very high levels of platelet-activating factor were found in peritoneal exudate from rats with pancreatitis. These data show an effective protective effect of BN-52021 on the hemodynamic impairment that follows pancreatitis induction, as well as a role of platelet-activating factor in these alterations.
Ais
G
G
Medical Research Institute, Fundación Jimenez Diaz-Consejo Superior de Investigaciones Cientificas, Madrid, Spain.
López-Farre
A
A
Gomez-Garre
D N
DN
Novo
C
C
Romeo
J M
JM
Braquet
P
P
López-Novoa
J M
JM
D000208:Acute Disease; D000818:Animals; D004224:Diterpenes; D046934:Ginkgolides; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D007783:Lactones / Q000494:pharmacology; D008297:Male; D010195:Pancreatitis / Q000503:physiopathology*; D010972:Platelet Activating Factor / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013152:Splanchnic Circulation
D004224:Diterpenes; D046934:Ginkgolides; D007783:Lactones; D010972:Platelet Activating Factor; C045856:ginkgolide B