Biomaterial Database

Hemodynamic effects of bradykinin antagonism in porcine gram-negative sepsis. 1995

P C Ridings, and H J Sugerman, and C R Blocher, and B J Fisher, and A A Fowler

Department of Surgery, Medical College of Virginia, Virginia Commonwealth University, Richmond, USA.

Activation of the kallikrein-kinin system in sepsis has long been recognized, but its role, beneficial or pathologic, has not been defined. Recently, however, specific bradykinin (BK) antagonists have become available and this study investigated the effects of a BK antagonist, NPC17731 (Scios-Nova) on systemic and pulmonary hemodynamics in a model of gram-negative sepsis. Anesthetized swine were studied for 5 h receiving a 1-h infusion of saline (controls, group 1, N = 8) or live Pseudomonas aeruginosa (septic, group 2, N = 8). Group 3 (treatment, N = 6) received NPC17731 (5 mg/kg initial bolus followed by 1 mg/kg hourly) just prior to the onset of sepsis. Group 2 animals showed a rapid decrease in systemic arterial pressure (SAP) from 30 min onward, and sustained significant hypotension from 2 h onward. In group 3, SAP fell similarly until 2 h then progressively rose, returning to baseline levels by 5 h. In contrast, cardiac index fell progressively from 3 h onward in groups 2 and 3. Systemic vascular resistance index (SVRI) fell significantly by 2 h in group 2 animals, recovering to baseline by 5 h. Group 3 showed a similar initial fall followed by a rebound increase in SVRI, which, at 5 h was significantly raised above the other groups. Group 2 developed significant, persistent pulmonary artery hypertension which was not reduced by NPC17731. The data imply a significant role for bradykinin in the pathogenesis of hypotension in septic shock in this model. Septic shock was reversed by a BK antagonist which increased peripheral resistance without affecting cardiac output.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D009842	Oligopeptides	Peptides composed of between two and twelve amino acids.	Oligopeptide
D001920	Bradykinin	A nonapeptide messenger that is enzymatically produced from KALLIDIN in the blood where it is a potent but short-lived agent of arteriolar dilation and increased capillary permeability. Bradykinin is also released from MAST CELLS during asthma attacks, from gut walls as a gastrointestinal vasodilator, from damaged tissues as a pain signal, and may be a neurotransmitter.	Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg,Bradykinin Acetate, (9-D-Arg)-Isomer,Bradykinin Diacetate,Bradykinin Hydrochloride,Bradykinin Triacetate,Bradykinin, (1-D-Arg)-Isomer,Bradykinin, (2-D-Pro)-Isomer,Bradykinin, (2-D-Pro-3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (2-D-Pro-7-D-Pro)-Isomer,Bradykinin, (3-D-Pro)-Isomer,Bradykinin, (3-D-Pro-7-D-Pro)-Isomer,Bradykinin, (5-D-Phe)-Isomer,Bradykinin, (5-D-Phe-8-D-Phe)-Isomer,Bradykinin, (6-D-Ser)-Isomer,Bradykinin, (7-D-Pro)-Isomer,Bradykinin, (8-D-Phe)-Isomer,Bradykinin, (9-D-Arg)-Isomer,Arg Pro Pro Gly Phe Ser Pro Phe Arg
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D013552	Swine	Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).	Phacochoerus,Pigs,Suidae,Warthogs,Wart Hogs,Hog, Wart,Hogs, Wart,Wart Hog
D016905	Gram-Negative Bacterial Infections	Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.	Bacterial Infections, Gram-Negative,Infections, Gram-Negative Bacterial,Bacterial Infection, Gram-Negative,Gram Negative Bacterial Infections,Gram-Negative Bacterial Infection,Infection, Gram-Negative Bacterial
D018805	Sepsis	Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by HYPOTENSION despite adequate fluid infusion, it is called SEPTIC SHOCK.	Bloodstream Infection,Pyaemia,Pyemia,Pyohemia,Blood Poisoning,Poisoning, Blood,Septicemia,Severe Sepsis,Blood Poisonings,Bloodstream Infections,Infection, Bloodstream,Poisonings, Blood,Pyaemias,Pyemias,Pyohemias,Sepsis, Severe,Septicemias