The Acute Effects of the Angiotensin-Converting Enzyme Inhibitor Enalaprilat on Flow Distribution
Summary
The primary objective of this study is to study the acute effects of angiotensin-converting enzyme inhibitor (ACEI) on systemic, pulmonary and cerebral blood flow in post bidirectional cavopulmonary connection (BCPC) patients.
Description
The intermediate stage of the bi-directional cavopulmonary connection (BCPC) in the management algorithm of single ventricle palliation is a unique and extraordinary physiologic condition. It places the superior vena caval blood flow into series with the lungs i.e. pulmonary blood flow is partially dependent on cerebral vascular flow and resistance. Differential reduction in the resistances of the systemic, cerebral and pulmonary vascular beds will result in re-equilibrium of relative blood flows which translate to alterations in arterial oxygen tension and perfusion pressure. This concept is demonstrated by the differential effects of carbon dioxide (CO2) and oxygen (O2). CO2 vasodilates and oxygen (O2) vasoconstricts the cerebral vascular bed; the opposite is true in the lungs. Furthermore, studies have demonstrated that arterial CO2 tension (PaCO2) at hypercarbic levels is favourable to normocarbia in increasing pulmonary, systemic and cerebral blood flows and reducing systemic vascular resistance in acute post BCPC patients.
Administration of angiotensin-converting enzyme inhibitor (ACEI) and other systemic vasodilator drugs are well established for treatment of patients with hypertension and congestive cardiomyopathy in both pediatric and adult populations. Favourable manipulation of the flow to the different vascular beds has been reported in children with significant intra-cardiac shunts in which pulmonary blood flow is decreased relative to the increase in systemic blood flow as a result of reduction of systemic vascular resistance.
Guided by similar principles, ACEI therapy is administered to patients with single ventricle physiology to redistribute relative blood flows across the pulmonary and systemic vascular beds. To date, there exists no study examining the hemodynamic effects of ACEI on relative blood flows in the setting of single ventricle physiology and in particular, no study demonstrates its benefits. The effects of ACEI are unknown on the equilibrium of relative cerebral, systemic and pulmonary blood flows in the post-BCPC state. A relative increase in systemic blood flow, as effected by ACEI, at the expense of cerebral blood flow may potentially adversely decrease pulmonary blood and ultimately reduce arterial oxygen tension. On the other hand, some data suggests that ACEI's improve cerebral autoregulation function; in which drop in blood pressure will signal a vasodilatory response in the cerebral vascular bed which may be particularly advantageous in BCPC patients.
Enalaprilat is the active diacid of the ACEI enalapril maleate. Doses of 0.01 to 0.06 mg/kg i.v. have been safely administered in pediatric studies. Onset of action is 15 minutes and duration of action is up to 12-24 hours. The pharmacokinetics of this drug are ideal for the purpose of this study. In our institution, all patients undergo routine cardiac catheterization after the BCPC procedure for hemodynamic assessment and angiography of cardiac structures to assess for eligibility for the Fontan operation.
Study Design
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Conditions
Hypertension
Intervention
Enalaprilat
Location
The Hospital for Sick Children
Toronto
Ontario
Canada
Status
Recruiting
Source
The Hospital for Sick Children
Results (where available)
Links
- Source: http://clinicaltrials.gov/show/NCT00741156
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
Enalaprilat
The active metabolite of ENALAPRIL and a potent intravenously administered angiotensin-converting enzyme inhibitor. It is an effective agent for the treatment of essential hypertension and has beneficial hemodynamic effects in heart failure. The drug produces renal vasodilation with an increase in sodium excretion.
Hypertension, Pregnancy-induced
A condition in pregnant women with elevated systolic (>140 mm Hg) and diastolic (>90 mm Hg) blood pressure on at least two occasions 6 h apart. HYPERTENSION complicates 8-10% of all pregnancies, generally after 20 weeks of gestation. Gestational hypertension can be divided into several broad categories according to the complexity and associated symptoms, such as EDEMA; PROTEINURIA; SEIZURES; abnormalities in BLOOD COAGULATION and liver functions.
Hypertension, Renovascular
Hypertension due to RENAL ARTERY OBSTRUCTION or compression.
Intracranial Hypertension
Increased pressure within the cranial vault. This may result from several conditions, including HYDROCEPHALUS; BRAIN EDEMA; intracranial masses; severe systemic HYPERTENSION; PSEUDOTUMOR CEREBRI; and other disorders.
Hypertension, Malignant
A condition of markedly elevated BLOOD PRESSURE with DIASTOLIC PRESSURE usually greater than 120 mm Hg. Malignant hypertension is characterized by widespread vascular damage, PAPILLEDEMA, retinopathy, HYPERTENSIVE ENCEPHALOPATHY, and renal dysfunction.
Clinical Trials
Angiogenesis Inhibitors and Hypertension: Clinical Aspects
The aim of the study is to find simple clinical and laboratory parameters to predict the development of hypertension and to elucidate the mechanism of hypertension during treatment with th...
Improving Practice Patterns for the Treatment of Hypertension
To improve the quality of hypertension care in our facility, while concurrently, examining the relative contribution of each aspect of a multi-factorial intervention designed to improve hy...
Study of Optimal Treatment Plan in Hypertensives With Anti-AT1-Receptor Autoantibody
The autoantibodies against AT1 receptor (ATR-AA), behaving like an agonist were detected in patients with hypertension. ATR-AA which can blocked by ARB may play a role in the pathogenesis...
ADAPT-Altering Diet for African American Populations to Treat Hypertension
The purpose of the study is to develop a culturally appropriate DASH intervention and test the effectiveness of the intervention lower blood pressure in a group of African American partici...
Hypertension in Management of Military Medicine
This study is a retrospective database review of primary care appointments of patients' charts with new diagnoses of hypertension.
PubMed Articles
The present study evaluated whether enalaprilat (the active form of enalapril, an angiotensin-converting enzyme inhibitor) activates B(1) receptors. We observed that the levels of B(1) receptor mRNA a...
This study investigated the influence of intracoronary enalaprilat on coronary microvascular function and peri-procedural outcome measures in patients with stable angina undergoing percutaneous corona...
The expression of the bradykinin (BK) B₁ receptor (B₁R), lacking in normal vascular tissues, is induced following innate immune system activation and chronic blockade of angiotensin converting enz...
