The cardiovascular hemodynamics and leukotriene kinetics during prostacyclin and anti-prostacyclin antibody infusions in septic shock.
This study evaluated whether or not prostacyclin (PGI2) was necessary or sufficient by itself in a pathophysiologic concentration to mediate the cardiovascular dysfunction of septic shock. Anesthetized adult swine received anesthesia only (ANESTHESIA CONTROL, n = 6); graded Aeromonas hydrophila, 10(10)/mL, infusion at 0.2 mL/kg/h that increased to 4.0 mL/kg/h over 3 h (SEPTIC SHOCK CONTROL, n = 6); pathophysiologic prostacyclin infusion to match septic shock control plasma levels without bacteremia (PGI2 INFUSION, n = 6), or graded Aeromonas hydrophila plus anti-prostacyclin antibody infusion (ANTI-PGI2-Ab INFUSION, n = 5). This graded porcine bacteremia model was 100% lethal after 4 h. Cardiovascular hemodynamics, arterial blood gases, and plasma levels of arachidonate metabolites were measured at baseline and hourly over a 4-h period. The results showed that PGI2 was not a necessary mediator of impaired cardiovascular hemodynamics in graded bacteremia, as anti-PGI2 antibody infusion did not improve the cardiac index, systemic vascular resistance, or peripheral oxygen balance in septic animals. Also, PGI2 was not sufficient alone to cause the cardiovascular dysfunction of sepsis, as pathophysiologic infusion of PGI2 did not reproduce such changes in normal animals. PGI2 blockade during bacteremia significantly increased LTC4D4E4, and LTB4 whereas PGI2 infusion suppressed LTC4D4E4 concentration, suggesting that endogenous PGI2 may blunt leukotriene release during septic shock. These results indicate a complex dynamic equilibrium among prostacyclin and leukotrienes in septic shock.
Tran
H S
HS
Department of Surgery and Surgical Critical Care, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Cooper Hospital/University Medical Center, Camden 08103, USA.
Quinn
J V
JV
Puc
M M
MM
Woolley
D S
DS
Puglisi
R N
RN
Slotman
G J
GJ
D015121:6-Ketoprostaglandin F1 alpha / Q000097:blood; D016980:Aeromonas hydrophila; D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D016470:Bacteremia / Q000209:etiology; D011464:Epoprostenol / Q000008:administration & dosage / Q000276:immunology / Q000633:toxicity*; D016905:Gram-Negative Bacterial Infections / Q000150:complications; D017997:Leukotriene C4 / Q000378:metabolism*; D017998:Leukotriene D4 / Q000378:metabolism*; D017999:Leukotriene E4 / Q000378:metabolism*; D012772:Shock, Septic / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D013552:Swine; D013929:Thromboxane B2 / Q000097:blood
D000906:Antibodies; D017997:Leukotriene C4; D013929:Thromboxane B2; D015121:6-Ketoprostaglandin F1 alpha; D017998:Leukotriene D4; D017999:Leukotriene E4; D011464:Epoprostenol