enalaprilat-anhydrous and Acute-Disease

Converting enzyme inhibitors meet most of the criteria required to be used in acute pulmonary edema. However, they could also induce deleterious effects on renal function and electrolytes. The purpose of this study was to evaluate the efficacy and safety of a single intravenous 2-hour infusion of enalaprilat (1 mg) after an acute pulmonary edema.. This was a placebo-controlled, randomized, double-blind study performed in 20 congestive heart failure patients (New York Heart Association class III or IV). Systemic and regional hemodynamic parameters, biological parameters, and blood gases were measured before and repeatedly after the onset of infusion. Compared with placebo, enalaprilat decreased pulmonary capillary wedge pressure (-37% versus -10%, P = .001), diastolic and mean systemic blood pressures (-21% versus 0%, P = .009, and -18% versus -1%, P = .026, respectively), diastolic and mean pulmonary blood pressures (-21% versus -8%, P = .040; -18% versus -9%, P = .046), and brachial and renal resistances (-44% versus -14%, P = .017, and -22% versus -2%, P = .014, respectively); increased brachial and renal blood flows (+77% versus +8%, P = .036, and +12% versus 0%, P = .043, respectively), arterial oxygen tension (+2% versus -16%, P = .041), and arterial oxygen saturation (+1% versus -2%, P = .045); and tended to decrease rate-pressure product (-19% versus -7%, P = .076), increase brachial artery diameter (+13% versus 0%, P = .081), and improve intrapulmonary shunt (-18% versus +16%, P = .080). Enalaprilat did not affect cardiac output or carotid or hepatosplanchnic hemodynamics.. Early administration of enalaprilat is effective and well tolerated in acute pulmonary edema.

Topics: Acute Disease; Aged; Double-Blind Method; Enalaprilat; Female; Gases; Heart Failure; Hemodynamics; Hormones; Humans; Injections, Intravenous; Male; Placebos; Pulmonary Circulation; Pulmonary Edema

To determine the cardiopulmonary actions of the intravenous administration of the angiotensin-converting enzyme inhibitor enalaprilat in hypertensive trauma patients.. Prospective, before/after trial.. Intensive care unit (ICU) of a university hospital.. Twenty critically injured and hypertensive ICU patients. All patients were receiving continuous sedation (fentanyl and midazolam) for at least 2 days before the injection of enalaprilat and had a mean arterial pressure (MAP) of > 95 mm Hg. "Responders" were defined as having a decrease in MAP of > 15% within 30 mins after enalaprilat injection.. Intravenous administration of 0.06 mg/kg of the angiotensin-converting enzyme inhibitor enalaprilat. Repeated doses were given when no sufficient response (decrease of MAP of > 15% within 30 mins after injection) was seen ("nonresponders").. In addition to standard hemodynamic monitoring, right ventricular hemodynamics and oximetric variables were also documented. Measurements were carried out before enalaprilat injection (during hemodynamic steady state [baseline values]) and at 1, 5, 10, 20, 30, 60, and 120 mins after enalaprilat administration.. MAP was successfully controlled in 17 of 20 patients (maximum decrease -27 mm Hg [-26%]). In the three other patients, even reinjection of enalaprilat (0.06 mg/kg) did not sufficiently reduce MAP. In the 17 responders, heart rate did not increase, whereas central venous pressure, pulmonary arterial pressure, and pulmonary artery occlusion pressure decreased significantly after intravenous administration of enalaprilat. Cardiac index changed only slightly (mean maximum +0.70 L/min/m2 [+18%]). Right ventricular ejection fraction increased from 36% to 45% (p < .05); right ventricular end-diastolic and end-systolic volume index decreased significantly. Both systemic and pulmonary vascular resistance indices decreased within the investigation period (-31% and -16%, respectively). Pao2/FIO2, intrapulmonary right-to-left shunting, and oxygen extraction ratio were not altered. Oxygen delivery index (+17%) and oxygen consumption index (+20%) increased during the investigation period (p < .04).. The intravenous administration of enalaprilat successfully decreased blood pressure in most of our patients. Mechanisms other than the renin-angiotensin system also appear to be involved in hypertensive, critically ill patients. Pulmonary function was not altered; right ventricular function, and both oxygen consumption and oxygen delivery improved in the enalaprilat responder group. Thus, the availability of intravenous enalaprilat seems to enlarge our armamentarium for treating hypertension in the critically ill patient.

Topics: Acute Disease; Adult; Aged; Analysis of Variance; Enalaprilat; Female; Heart; Hemodynamics; Humans; Hypertension; Injections, Intravenous; Lung; Male; Middle Aged; Prospective Studies; Time Factors; Wounds and Injuries

To evaluate the acute effects of intravenous enalaprilat infusion in critically ill patients with intractable heart failure after acute myocardial infarction.. Prospective, consecutive sample, before-after trial.. Medical intensive care unit in a university hospital.. Eight consecutive patients with intractable acute heart failure after acute myocardial infarction. All study patients continued receiving inotropic, vasodilating, and diuretic medication at a constant rate. Six patients received steady intermittent mandatory ventilation and two patients were on a continuous positive airway pressure mask during the investigation, all with constant positive end-expiratory pressure. Heart failure was defined as intractable if the pulmonary artery occlusion pressure remained > 20 mm Hg despite this conventional therapy.. Enalaprilat was infused at a rate of 1 mg/hr until the pulmonary artery occlusion pressure decreased by > or = 20%.. Central hemodynamics, oxygenation, and hormonal regulation (plasma renin activity, plasma norepinephrine, epinephrine, endothelin, atrial natriuretic peptide, and vasopressin concentrations, serum angiotensin-converting enzyme activity, and serum concentrations of aldosterone) were assessed at baseline before enalaprilat infusion, and repeatedly during 2 hrs after the infusion. The statistical analysis was performed with analysis of variance for repeated measurements. Enalaprilat infusion (median dose 0.3 mg and infusion time 21 mins) caused significant but short-lasting decreases in pulmonary artery occlusion pressure (p = .007), mean arterial pressure (p = .003), mean pulmonary arterial pressure, and rate pressure product. These findings coincided with inhibition of serum angiotensin-converting enzyme activity, an increase in plasma renin activity, and a decrease in plasma endothelin concentrations (p = .041). Enalaprilat had no significant effects on the other hormones studied. Cardiac output and stroke volume index, venous admixture, oxygen extraction ratio, and mixed venous and arterial oxygen saturations remained unchanged.. Adding enalaprilat to conventional therapy makes it possible to transiently relieve pulmonary congestion while maintaining cardiac function and systemic oxygenation. The decrease in plasma endothelin concentrations may have further clinical implications, because endothelin is known to have potent vasoconstricting effects on the coronary circulation and it may also contribute to the extension of myocardial infarction. Whether these observed benefits can be maintained with repeated bolus injections or with continuous infusion of enalaprilat, remains to be settled.

Topics: Acute Disease; Aged; Combined Modality Therapy; Enalaprilat; Female; Finland; Heart Failure; Hemodynamics; Humans; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Statistics as Topic; Time Factors

Blockade of the renin-angiotensin system (RAS) has been shown to alleviate inflammatory processes in the gastrointestinal tract. The aim of this study was to determine if blockade of the RAS would be effective in an immunologically relevant colitis model, and to compare outcome with an acute colitis model.. In the DSS model, weight loss and histologic score for CCG-203025 were better than with placebo. In the IL10-/-model, ACE-I suppressed histologic damage better than CCG-203025. Both ACE-I and CCG-203025 reduced pro-inflammatory cytokines and chemokines.. This study demonstrated the therapeutic efficacy of both ACE-I and AT1aR-A for preventing the development of both acute and immunologically relevant colitis.

Topics: Acute Disease; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Animals; Colitis; Cyclooxygenase Inhibitors; Disease Models, Animal; Enalaprilat; Losartan; Mice; Mice, Inbred C57BL; Piroxicam; Renin-Angiotensin System

This study investigates the effect of angiotensin-converting-enzyme inhibition by intravenous enalaprilat (100 micrograms/kg) on splanchnic vascular capacitance during acute left ventricular failure induced by coronary microembolization in alpha-chloralose/urethan anesthetized dogs. Changes in hepatic and splenic vascular volumes were determined from organ diameters (sonomicrometry) at 15, 30, and 45 min after enalaprilat injection. Changes in vascular capacitance were assessed from organ pressure-diameter curves obtained during transient hepatic outflow occlusion. Thirty minutes after enalaprilat, hepatic volume was increased by 52 +/- 14 ml (P < 0.01), and portal and hepatic vein pressures were decreased from 10.2 +/- 0.9 to 8.7 +/- 0.8 mmHg (P < 0.01) and from 3.9 +/- 1.6 to 3.1 +/- 0.7 mmHg (P < 0.05), respectively. Splenic volume did not change. Enalaprilat shifted the hepatic pressure-diameter curve upward, resulting in a larger hepatic volume at any given pressure. Curve intercept was increased, suggesting an increase in unstressed vascular volume. Curve slope was unchanged. In conclusion, enalaprilat increased hepatic vascular volume during acute left ventricular failure in dogs. The pressure-diameter curve shift suggests a reduction in the smooth muscle tone of hepatic capacitance vessels.

Topics: Acute Disease; Animals; Cardiac Output, Low; Coronary Thrombosis; Dogs; Enalaprilat; Female; Hemodynamics; Male; Myocardial Ischemia; Splanchnic Circulation; Vascular Resistance

Plasma levels of endothelin (ET), plasma renin activity (PRA) and angiotensin II (Ang II) were measured in anaesthetized marmosets exposed to acute aortic stenosis proximal to the renal arteries. In vehicle experiments, ET rose from 5 +/- 2 to 38 +/- 4 pg ml-1, PRA from 5 +/- 2 to 99 +/- 21 ng ml-1 h-1 and Ang II from 21 +/- 4 to 213 +/- 76 pg ml-1. Administration of renin inhibitor and angiotensin converting enzyme inhibitor reduced PRA and Ang II to control levels, while the plasma levels of ET increased further (51 +/- 10 and 71 +/- 16 pg ml-1, respectively). During aortic stenosis the two isoforms ET-1 and ET-3 appeared in the circulation, while in conscious control animals only ET-1 was found. It is concluded that the increased plasma levels of ET in our primate model could not be ascribed to the increased circulating levels of PRA and Ang II.

Topics: Acute Disease; Angiotensin II; Animals; Aortic Valve Stenosis; Blood Pressure; Callithrix; Carotid Arteries; Chromatography, High Pressure Liquid; Enalaprilat; Endothelins; Female; Femoral Artery; Male; Osmolar Concentration; Renin; Renin-Angiotensin System