Hemodynamic, renal, and hormonal actions of aprotinin in an ovine model of septic shock.
METHODS
Previous studies documented activation of protease enzymes such as the plasma kallikrein-kinin system in endotoxemia and sepsis, both in experimental animals and in patients. We investigated the actions of aprotinin (a protease inhibitor that binds to plasma kallikrein) on systemic hemodynamics and renal function, in an ovine model of septic shock. Aprotinin was infused intravenously in high dosage (1 x 10(6) kallikrein inhibitor units [KIU] loading, 200,000 KIU/hr), commencing 30 mins after surgical induction of sepsis (cecal ligation and puncture).


RESULTS
In the control group (n = 6), there were significant decreases with time in BP and systemic vascular resistance, an increase in pulmonary artery pressure, reductions in creatinine clearance and sodium excretion, and an increase in plasma renin activity. In aprotinin-treated animals (n = 6), none of these changes occurred. There were significant between-group differences (controls vs. treatment) for mean arterial pressure, pulmonary artery pressure, and plasma renin activity.


CONCLUSIONS
In this large animal model of septic shock, which reproduces the important features of clinical sepsis, treatment with aprotinin after the initiation of sepsis appears beneficial in relation to systemic hemodynamics, renal function, and hormonal stimulation, with no evidence of adverse effects.
Cumming
A D
AD
Department of Medicine, University of Edinburgh, Royal Infirmary, UK.
Nimmo
G R
GR
D000704:Analysis of Variance; D000818:Animals; D007611:Aprotinin / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D006439:Hemodynamics / Q000187:drug effects; D007262:Infusions, Intravenous; D016234:Kallikrein-Kinin System / Q000187:drug effects* / Q000502:physiology; D007610:Kallikreins / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000652:urine; D007668:Kidney / Q000187:drug effects* / Q000503:physiopathology; D012756:Sheep; D012757:Sheep Diseases / Q000188:drug therapy* / Q000503:physiopathology; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology
D007611:Aprotinin; D007610:Kallikreins