INFLUENCE OF INTRAVENOUS ADMINISTRATION OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITOR ENALAPRILAT ON CARDIOVASCULAR MEDIATORS IN CARDIAC-SURGERY PATIENTS

The renin-angiotensin system (RAS) is important in controlling and mai ntaining cardiovascular homeostasis. In a randomized, prospective stud y, the response to intravenous (IV) administration of the angiotensin- converting enzyme (ACE) inhibitor enalaprilat (0.06 mg/kg) on importan t controllers of the circulation was investigated in 24 patients under going aortocoronary bypass grafting with a mean arterial blood pressur e (MAP) > 85 mm Hg after induction of anesthesia. Fourteen patients re ceived saline solution as placebo (control group). Endothelin (ET), at rial natriuretic peptide (ANP), catecholamine (epinephrine, norepineph rine) plasma levels, and ACE activity were measured from arterial bloo d sampled before injection of enalaprilat or NaCl solution (baseline v alues), 10 min and 30 min thereafter, immediately before the start of cardiopulmonary bypass (CPB), immediately after CPB, and at the end of surgery. MAP, heart rate (HR), cardiac index (CI), and systemic vascu lar resistance (SVR) were also monitored. ACE activity was similar at baseline in both groups; after IV injection of enalaprilat, it signifi cantly decreased (from 35.1 +/- 11 to 4.4 +/- 1.0 U . min(-1). L(-1) 3 0 min after injection) and remained reduced until the end of the opera tion (295 +/- 31 min after injection). ANP plasma levels were increase d beyond normal (> 100 pg/mL) at baseline in both groups. They increas ed significantly in the control patients, but remained almost unchange d in the enalaprilat-treated patients within the entire study period. Plasma concentration of ET also increased only in the control group an d was increased after CPB (8.6 +/- 1.2 pg/mL at the end of the operati on). Starting from similar catecholamine plasma levels at baseline, ep inephrine and norepinephrine concentrations increased in the control p atients, being significantly different from the plasma levels of the e nalaprilat-treated group. IV enalaprilat significantly decreased MAP f rom 100 +/- 7 mm Hg at baseline to 70 +/- 7 mm Hg prior to start of CP B without showing a reflex increase in HR. CI increased and SVR decrea sed in the prebypass period in these patients (P < 0.05). It is conclu ded that IV administration of enalaprilat was effective in reducing bl ood pressure in cardiac surgery patients. In addition, it beneficially influenced endocrinologic regulators of macro- and microcirculation b y blunting the increase of systemic and local vasoactive substances, w hich is normally observed in this situation.