Vasoactive effects of aprotinin.

Area of Science:

• Pharmacology
• Nephrology
• Critical Care Medicine

Background:

• Activation of the plasma kallikrein-kinin system is linked to systemic vasodilation in septic shock and hepatic cirrhosis.
• This vasodilation can lead to neuroendocrine activation and impaired renal function.

Purpose of the Study:

• To investigate the effects of the protease inhibitor aprotinin on experimental septic shock and patients with hepatic cirrhosis and ascites.
• To determine if aprotinin can reverse pathological vasodilation and improve renal function in these conditions.

Main Methods:

• Aprotinin administration in experimental sepsis (early and late) and in patients with cirrhosis and ascites.
• Monitoring of hemodynamic parameters (arterial pressure, systemic vascular resistance - SVR), renal function (creatinine clearance, glomerular filtration rate, renal plasma flow, sodium excretion), and plasma renin activity (PRA).

Main Results:

• In early sepsis, aprotinin maintained arterial pressure, SVR, creatinine clearance, and sodium excretion, while blocking increases in pulmonary artery pressure and PRA.
• Late administration of aprotinin in sepsis rapidly restored arterial pressure and SVR.
• In cirrhosis, aprotinin increased SVR in patients with low baseline values and improved renal function and sodium excretion, suppressing PRA.

Conclusions:

• Aprotinin effectively reverses pathological systemic vasodilation in both septic shock and hepatic cirrhosis.
• The therapeutic effects of aprotinin are associated with reduced renin release and improved renal function in these conditions.