Effect of the serine protease inhibitor, aprotinin, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites.

Abstract

1. Previous studies have documented activation of protease enzymes, such as the plasma kallikrein-kinin system, in hepatic cirrhosis. Increased plasma kinin generation could contribute to pathological systemic vasodilatation in cirrhosis, and reduced systemic vascular resistance has been suggested as a trigger to renal sodium retention in this disease. We investigated the effect of aprotinin, a protease inhibitor which binds to plasma kallikrein, on systemic haemodynamics and renal function in patients with hepatic cirrhosis and ascites. 2. Aprotinin was infused intravenously in high dosage (2 x 10(6) kallikrein inhibitory units loading, 1 x 10(6) kallikrein inhibitory units/h). 3. Of 13 patients, 10 had a low systemic vascular resistance (< 1200 dyn s cm-5) at baseline. In this group, eight showed an increase in systemic vascular resistance during aprotinin infusion. Overall, the increase in systemic vascular resistance was significant, and there was a small but significant increase in mean arterial pressure. In all patients, there were increases in renal plasma flow, glomerular filtration rate, and absolute and fractional urinary sodium excretion during aprotinin infusion. 4. Plasma renin activity, plasma angiotensin II and plasma aldosterone fell significantly during aprotinin infusion. Plasma prekallikrein, plasma noradrenaline and plasma atrial natriuretic peptide did not change. Plasma aprotinin concentration was 209 +/- 11 kallikrein inhibitory units/ml at the end of the infusion. 5. Before and during the infusion, there was a significant negative correlation between systematic vascular resistance and plasma renin activity. There was a positive correlation between the change in systemic vascular resistance and the change in renal plasma flow during aprotinin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

• Authors: A MacGilchrist, K J Craig, P C Hayes, A D Cumming
• Journal: Clinical science (London, England : 1979) (Clin Sci (Lond)) Vol. 87 Issue 3 Pg. 329-35 (Sep 1994) ISSN: 0143-5221 [Print] England
• PMID: 7525142 (Publication Type: Journal Article)

Chemical References

• Angiotensin II
• Aldosterone
• Aprotinin
• Sodium
• Renin

Topics

• Adult
• Aged
• Aldosterone (blood)
• Angiotensin II (blood)
• Aprotinin (therapeutic use)
• Ascites (blood, drug therapy, urine)
• Blood Pressure (drug effects)
• Female
• Glomerular Filtration Rate (drug effects)
• Humans
• Liver Cirrhosis (blood, drug therapy, urine)
• Liver Cirrhosis, Alcoholic (blood, drug therapy, urine)
• Male
• Middle Aged
• Regional Blood Flow (drug effects)
• Renal Circulation (drug effects)
• Renin (blood)
• Sodium (urine)
• Vascular Resistance (drug effects)