enalaprilat-anhydrous and Coronary-Artery-Disease

This study was undertaken to evaluate the effect of enalaprilat infusion on hemodynamics and renal function during cardiopulmonary bypass (CPB).. Thirty adults undergoing CPB were randomly allocated into 2 groups. All patients received the same anesthetic protocol and same dopamine infusion protocol (2 mg/kg(-1)/min(-1)) during the study. In addition to dopamine infusion 15 patients received enalaprilat infusion (0.06 mg/kg(-1)/hr(-1)) during CPB. Blood creatinine, urea levels, and creatinine clearance (CLcr) were measured and cardiac output (CO) was calculated by echocardiography preoperatively and on the 6th postoperative day. Mean arterial pressure (MAP), central venous pressure (CVP), systemic vascular resistance (SVR) measurements were recorded during the operation and during postoperative 24 hours.. In the control group postoperative blood creatinine and urea levels were significantly higher and CLcr measurements were significantly lower than the preoperative values (p<0.05). These values did not change in the enalaprilat group. Mean arterial pressure was similar in both groups (p>0.05), but SVR was lower (p<0.05) and CVP was higher (p<0.05) in the enalaprilat group than in the control group. In the enalaprilat group postoperative CO measurements were higher than the preoperative values (p<0.05).. Our results demonstrate that enalaprilat infusion during CPB improves renal function and CO measurements in the early postoperative period.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiac Output; Cardiopulmonary Bypass; Coronary Artery Disease; Creatinine; Enalaprilat; Female; Hemodynamics; Humans; Infusions, Intravenous; Kidney; Kidney Function Tests; Male; Middle Aged; Treatment Outcome; Ultrasonography; Urea

The aim of this study was to examine whether angiotensin-converting enzyme (ACE) inhibition improves coronary endothelial dysfunction in patients with atherosclerosis and its risk factors and whether this was related to the ACE insertion-deletion (I/D) polymorphism.. In 56 patients with atherosclerosis or its risk factors, we studied endothelium-dependent responses with acetylcholine and endothelium-independent function with sodium nitroprusside, before and after ACE inhibition with enalaprilat. Enalaprilat did not alter either resting coronary tone or vasodilation with sodium nitroprusside. However, it potentiated the coronary microvascular and epicardial responses with acetylcholine; coronary blood flow increased from 82+/-7 to 90+/-8 mL/min (P=0.05) after enalaprilat. Patients with depressed endothelial function (P<0.001) and those with ACE DD or ID genotypes (P=0.002) but not those homozygous for the I allele had the greatest improvement by multivariate analysis. Similarly, acetylcholine-mediated epicardial vasomotion improved in segments that initially constricted (endothelial dysfunction): from -10.1+/-1% to -1.4+/-2% (P<0.001) after enalaprilat. No augmentation was observed in segments that dilated (normal endothelial dysfunction) with acetylcholine. Patients with the D allele, hypercholesterolemia, and smokers (all P<0.05) had greater improvement.. Acute ACE inhibition improves coronary epicardial and microvascular endothelium-dependent vasomotion in patients with atherosclerosis or its risk factors who have endothelial dysfunction and presence of the D allele.

Topics: Acetylcholine; Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Coronary Circulation; Coronary Disease; Enalaprilat; Endothelium, Vascular; Gene Deletion; Genotype; Humans; Middle Aged; Multivariate Analysis; Nitroprusside; Peptidyl-Dipeptidase A; Polymorphism, Genetic; Predictive Value of Tests; Risk Factors; Treatment Outcome; Vasodilator Agents

Atherosclerosis is associated with vascular endothelial dysfunction and reduced nitric oxide (NO) activity. Enhancement of NO activity may have an antiatherogenic action. This study was performed to determine whether angiotensin-converting enzyme (ACE) inhibition improves peripheral vascular NO activity in patients with atherosclerosis. In the femoral circulation of 43 patients with atherosclerosis and 10 controls, we studied endothelium-dependent vasodilation with bradykinin and acetylcholine, and endothelium-independent vasodilation with sodium nitroprusside before and after enalaprilat. In 22 patients, we repeated these infusions in the presence of L-N(G) monomethyl arginine (L-NMMA). Doppler-femoral artery flow velocity was measured. Before ACE inhibition, acetylcholine responses were depressed in patients with atherosclerosis compared with controls (p = 0.03). Enalaprilat did not alter femoral vascular tone at rest or vasodilation with sodium nitroprusside, but potentiated bradykinin-mediated vasodilation in patients (p<0.001) and controls (p = 0.02). Acetylcholine-mediated vasodilation was augmented only in patients (p<0.001), but not in control subjects. L-NMMA inhibited the potentiation by enalaprilat of acetylcholine and bradykinin responses. This study demonstrates that ACE inhibition selectively improves endothelial dysfunction in human atherosclerosis by enhancing NO activity. The antithrombotic and antiproliferative effects of NO may reduce adverse manifestations related to atherosclerosis during long-term therapy.

Topics: Angiotensin-Converting Enzyme Inhibitors; Coronary Artery Disease; Enalaprilat; Endothelium, Vascular; Enzyme Inhibitors; Female; Femoral Artery; Humans; Male; Middle Aged; Nitric Oxide; omega-N-Methylarginine; Reproducibility of Results; Vascular Resistance; Vasodilation

This study was performed to determine whether angiotensin converting enzyme (ACE) inhibition improves endothelium-dependent flow-mediated vasodilation in patients with atherosclerosis or its risk factors and whether this is mediated by enhanced bradykinin activity.. Abnormal coronary vasomotion due to endothelial dysfunction contributes to myocardial ischemia in patients with atherosclerosis, and its reversal may have an antiischemic action. Previous studies have shown that ACE inhibition improves coronary endothelial responses to acetylcholine, but whether this is accompanied by improved responses to shear stress remains unknown.. In 19 patients with mild atherosclerosis, metabolic vasodilation was assessed during cardiac pacing. Pacing was repeated during separate intracoronary infusions of low-dose bradykinin (BK) and enalaprilat. Endothelium-dependent and -independent vasodilation was estimated with intracoronary BK and sodium nitroprusside respectively.. Enalaprilat did not alter either resting coronary vascular tone or dilation with sodium nitroprusside, but potentiated BK-mediated dilation. Epicardial segments that constricted abnormally with pacing (-5+/-1%) dilated (3+/-2%) with pacing in the presence of enalaprilat (p = 0.002). Similarly, BK at a concentration (62.5 ng/min) that did not alter resting diameter in the constricting segments also improved the abnormal response to a 6+/-1% dilation (p < 0.001). Cardiac pacing-induced reduction in coronary vascular resistance of 27+/-4% (p < 0.001) remained unchanged after enalaprilat.. Thus ACE inhibition: A) selectively improved endothelium-dependent but not-independent dilation, and B) abolished abnormal flow-mediated epicardial vasomotion in patients with endothelial dysfunction, in part, by increasing endogenous BK activity.

Topics: Adenosine; Angiotensin-Converting Enzyme Inhibitors; Blood Flow Velocity; Bradykinin; Cardiac Catheterization; Coronary Artery Disease; Coronary Vessels; Echocardiography, Doppler; Enalaprilat; Endothelium, Vascular; Female; Humans; Injections, Intra-Arterial; Male; Middle Aged; Muscle, Smooth, Vascular; Nitroprusside; Peptidyl-Dipeptidase A; Pericardium; Vasodilation; Vasodilator Agents