enalaprilat-anhydrous and Coronary-Disease

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Captopril; Coronary Disease; Enalaprilat; Hemodynamics; Humans; Hypertension; Myocardial Infarction

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

The first dose of angiotensin-converting enzyme (ACE) inhibitors may trigger a considerable fall of blood pressure in chronic heart failure. The response may be dose-related. To determine hemodynamic and systemic oxygenation effects of low-dose enalaprilat, we administered intravenous enalaprilat (0.004 mg/kg) as bolus (group B) or continuous 1-hour infusion (group C) in 20 patients with congestive heart failure due to ischemic heart disease with acute decompensation refractory to inotropic, vasodilator and diuretic therapy. Hemodynamic and systemic oxygenation variables were recorded at baseline (+0 min), +30, +60, +120, +180, and +360 min after the start of intervention. Mean arterial pressure (MAP) (p < 0. 001), mean pulmonary artery pressure (MPAP) (p < 0.001), pulmonary artery occlusion pressure (PAOP) (p < 0.001), oxygen extraction ratio (ER) (p < 0.026) decreased regardless of enalaprilat application. Compared to group B, there was in group C prolonged decrease of MAP, MPAP, PAOP, ER and increase of pulmonary artery oxyhemoglobin saturation in regard to baseline values. Cardiac index, heart rate, central venous pressure and oxygen consumption index did not change. A low dose of intravenous enalaprilat (0.004 mg/kg) can be used to safely improve hemodynamics and systemic oxygenation in congestive heart failure due to ischemic heart disease with acute refractory decompensation.

Topics: Aged; Aged, 80 and over; Angiotensin-Converting Enzyme Inhibitors; Coronary Disease; Drug Administration Schedule; Drug Therapy, Combination; Enalaprilat; Female; Heart Failure; Hemodynamics; Humans; Infusions, Intravenous; Male; Middle Aged; Oxygen; Pilot Projects

The aim of this study was to assess the sigmoid line of elasticity in the human aorta.. The pressure-diameter relation was measured in the descending aorta in 120 subjects. In an additional group of 6 subjects, transient vena caval occlusion produced 5 sets of pressure-diameter data. We found that the best fit curve of the pooled pressure-diameter data was a third-order polynomial. A polynomial equation was used to calculate the sigmoid line of elasticity in the entire population and after the administration of diltiazem (15 patients) or enalaprilat (10 patients). The sigmoid line of elasticity was significantly different with respect to age (P<0.001), history of hypertension (P<0.004), and hypercholesterolemia (P<0.02). The difference between the transition point and the peak systolic pressure was increased in normal subjects compared with patients (P<0.0001). The sigmoid line shifted leftward and upward with diltiazem, but it remained unchanged with enalaprilat. During an average of 3 years of follow-up, 19 of 88 patients developed stroke (n=4), unstable angina (n=8), acute myocardial infarction (n=4), or acute pulmonary edema (n=3).. This approach provides a quantitative evaluation of the aortic line of elasticity, which can differentiate the intrinsic from the extrinsic aortic elastic properties. Furthermore, it is a powerful and independent risk factor for cardiovascular events.

Topics: Aorta; Blood Pressure; Coronary Disease; Data Interpretation, Statistical; Diltiazem; Elasticity; Enalaprilat; Heart Failure; Humans; Hypertension; Regression Analysis; Risk Factors; Vasodilator Agents

The pump function during exercise can be disturbed not only in hypertensives with coronary artery disease (CAD), but also in those with a normal angiogram.. In 10 hypertensive patients (group 1; aged 52+/-4 years, 1 men, 9 women) with ST segment depression during exercise and concomitant angina pectoris but normal coronary angiograms (microangiopathy) and without left ventricular hypertrophy (LVMI <110 g/m2), the left ventricular function at rest and during exercise was studied by cardiac catheterization and compared with 10 hypertensives with CAD (group 2; aged 57.6+/-4 years, 7 men, 3 women) and 10 hypertensives without ST segment depression (group 3; aged 51.8+/-5 years, 10 men) before and after intravenous administration of 1.25 mg enalaprilat.. The pulmonary capillary wedge pressure (PCWP) was normal at rest and pathologically increased at 60+/-13 W only in groups 1 and 2 (27.2+/-3 and 32.2+/-8 mm Hg, respectively), but not in group 3 (12.2+/-4 mm Hg; p<0.001). At the identical load level, the PCWP in patients with microangiopathy (group 1) was significantly (p<0.01) reduced after enalaprilat (-21.7%) and even normalized in 5 of 10 patients. This was accompanied by a significant (p>0.01) decrease in ST segment depression (-73.9%) and in the occurrence of angina pectoris, despite the fact that the rate-pressure product as a measure of myocardial oxygen consumption was significantly (p<0.05) increased. Also in patients with CAD enalaprilat had a significant effect on PCWP (p<0.01), ST segment depression (p<0.01), occurrence of angina pectoris (p<0.001), cardiac index (p<0.05), and stroke index (p<0.05) during exercise. In group 3 there were no significant changes in PCWP, cardiac index, and stroke index after enalaprilat either at rest or during exercise.. The functional improvement under the action of enalaprilat suggests that the advantages of the drug may be mediated mainly through an increase in myocardial blood flow and that angiotensin II might be involved in the restricted increase in coronary blood flow during dynamic exercise in hypertensives with coronary microangiopathy.

Topics: Angina Pectoris; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Coronary Disease; Enalaprilat; Exercise Test; Female; Hemodynamics; Humans; Hypertension; Male; Microcirculation; Middle Aged; Ventricular Dysfunction, Left

The present study aimed to determine the role of nitric oxide (NO) and angiotensin-converting enzyme (ACE) in bradykinin (BK)-induced dilation of human coronary arteries in vivo.. BK, produced by way of the kinin-kallikrein system, causes endothelium-dependent vasodilation. However, little is known about the mechanism of BK-induced dilation of coronary arteries in humans in vivo.. The effects of an inhibitor of NO synthesis and of an ACE inhibitor on BK-induced coronary vasodilation were examined in 20 patients who had no significant atherosclerotic stenosis in the artery under study. Lumen diameters of the large epicardial coronary arteries and coronary blood flow (CBF) were measured by quantitative coronary arteriography and intracoronary Doppler technique.. Intracoronary infusion of BK (0.6 and 2.0 micrograms/min) increased coronary artery diameter and CBF with no change in arterial pressure or heart rate. The BK-induced increases in coronary artery diameter and CBF were significantly reduced (p < 0.01) after pretreatment with NG-monomethyl-L-arginine (200 mumol) and were significantly increased (p < 0.01) after pretreatment with enalaprilat (50 micrograms).. BK-induced dilation of human large epicardial and resistance coronary arteries is mediated by NO and increased by prior ACE inhibition.

Topics: Aged; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Coronary Angiography; Coronary Disease; Coronary Vessels; Enalaprilat; Female; Humans; Male; Middle Aged; Nitric Oxide; Nitric Oxide Synthase; omega-N-Methylarginine; Peptidyl-Dipeptidase A; Ultrasonography, Doppler; Ultrasonography, Interventional; Vasodilation

We determined the relationship between cardiac angiotensin-converting enzyme (ACE) inhibition and anti-ischemic efficacy of several structurally different ACE inhibitors or their prodrug esters perfused through the isolated rat heart. Seven ACE inhibitors inhibited cardiac ACE to varying degrees due to differences in uptake during perfusion through nonischemic rat hearts. Zofenopril-sulfhydryl and fosinoprilic acid were the most effective of the free inhibitors. Among the prodrugs, zofenopril and S-benzoylcaptopril, hydrolyzed rapidly by cardiac esterase, were more effective than their component ACE-inhibitors, whereas fosinopril, ramipril and enalapril were poorly active. For studies in ischemic rat hearts, vehicle or drug treatment was initiated 10 min before a 25-min period of global ischemia and during a 30-min reperfusion period. Of five unesterified ACE inhibitors studied for anti-ischemic activity, only captopril and zofenopril-sulfhydryl were found to improve postischemic contractile function and reduce cell death in the isolated rat hearts. Fosinoprilic acid, ramiprilat and enalaprilat were not cardioprotective at high perfusion concentrations, despite the fact that nearly complete inhibition of cardiac ACE was achieved with all of the compounds studied. The S-benzoyl prodrugs of zofenopril-sulfhydryl and captopril were at least as potent as their component ACE inhibitors in reducing ischemic-reperfusion damage in the same model. Neither zofenopril nor captopril, however, had any effect on coronary flow before or after ischemia. Thus, it appears that the cardioprotective effects of zofenopril and captopril are independent of cardiac ACE inhibition or, at least, that ACE inhibition alone is not sufficient. Both captopril and zofenopril are sulfhydryl-containing compounds whereas the inactive compounds are not; and, thus, this group appears to be important in mediating their cardioprotective actions.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Captopril; Coronary Disease; Drug Stability; Enalaprilat; Fosinopril; Heart; In Vitro Techniques; Male; Myocardium; Organophosphorus Compounds; Prodrugs; Proline; Pyrroles; Ramipril; Rats; Rats, Inbred Strains; Sulfhydryl Compounds

The converting enzyme not only converts angiotensin I into angiotensin II but also metabolizes bradykinin. Furthermore, the effects of ischemia on myocardial tissue damage can be modulated by converting enzyme inhibitors. It is unknown whether these effects of ACE-inhibitors are due to increased bradykinin production. In this paper we describe the effects of captopril on bradykinin production in the ischemic isolated rat heart. The reduced deleterious effects of ischemia by captopril were associated with a stimulated bradykinin production. Beneficial effects of bradykinin could be due to an improved perfusion or to an effect on cellular metabolism. Therefore, we conclude that this effect on kinins by ACE-inhibitors is of importance in modulating tissue damage during ischemia.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Bradykinin; Captopril; Coronary Circulation; Coronary Disease; Coronary Vessels; Enalaprilat; Indomethacin; Myocardium; Rats; Vasodilation