Influence of Intravenous Administration of Angiotensin-Converting Enzyme Inhibitor Enalaprilat on Cardiovascular Mediators in Cardiac Surgery Patients

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Abstract
The renin-angiotensin system (RAS) is important in controlling and maintaining cardiovascular homeostasis. In a randomized, prospective study, the response to intravenous (IV) administration of the angiotensin-converting enzyme (ACE) inhibitor enalaprilat (0.06 mg/kg) on important controllers of the circulation was investigated in 24 patients undergoing aortocoronary bypass grafting with a mean arterial blood pressure (MAP) > 85 mm Hg after induction of anesthesia. Fourteen patients received saline solution as placebo (control group). Endothelin (ET), atrial natriuretic peptide (ANP), catecholamine (epinephrine, norepinephrine) plasma levels, and ACE activity were measured from arterial blood sampled before injection of enalaprilat or NaCl solution (baseline values), 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 vascular resistance (SVR) were also monitored. ACE activity was similar at baseline in both groups; after IV injection of enalaprilat, it significantly decreased (from 35.1 +/- 11 to 4.4 +/- 1.0 U . min(-1). L(-1) 30 min after injection) and remained reduced until the end of the operation (295 +/- 31 min after injection). ANP plasma levels were increased beyond normal (> 100 pg/mL) at baseline in both groups. They increased significantly in the control patients, but remained almost unchanged in the enalaprilat-treated patients within the entire study period. Plasma concentration of ET also increased only in the control group and was increased after CPB (8.6 +/- 1.2 pg/mL at the end of the operation). Starting from similar catecholamine plasma levels at baseline, epinephrine and norepinephrine concentrations increased in the control patients, being significantly different from the plasma levels of the enalaprilat-treated group. IV enalaprilat significantly decreased MAP from 100 +/- 7 mm Hg at baseline to 70 +/- 7 mm Hg prior to start of CPB without showing a reflex increase in HR. CI increased and SVR decreased in the prebypass period in these patients (P < 0.05). It is concluded that IV administration of enalaprilat was effective in reducing blood pressure in cardiac surgery patients. In addition, it beneficially influenced endocrinologic regulators of macro- and microcirculation by blunting the increase of systemic and local vasoactive substances, which is normally observed in this situation.