The Acute Effects of the Angiotensin-converting Enzyme Inhibitor Enalaprilat on Flow Distribution
Condition: Hypertension; Congestive Cardiomyopathy
MeSH terms: Hypertension; Cardiomyopathies; Cardiomyopathy, Dilated
Study type: Interventional
Phase: Phase 3

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.
    

Detailed 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.
    

Intervention name(s): Enalaprilat
Intervention type(s): Drug
Intervention description(s): Enalaprilat will be administered intravenously i.v. 0.005 - 0.01 mg/kg i.v. over 1 minute
Other intervention name(s): Vasotec
Intervention MeSH terms: Enalaprilat; Enalapril
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: pediatric; hypertension; congestive cardiomyopathy; angiotensin-converting enzyme inhibitor; cardiac catheterization