Role of Endothelin in Microvascular Dysfunction Following PCI for NSTEMI
Condition: Myocardial Reperfusion Injury
MeSH terms: Reperfusion Injury; Non-ST Elevated Myocardial Infarction; Myocardial Reperfusion Injury
Intervention: BQ-123; Placebo
Intervention description: BQ-123 is a cyclic peptide consisting of five amino acids. BQ-123 will be infused at 300 nmol/min for 20 minutes prior to percutaneous coronary intervention (PCI).; Subjects randomized to the placebo arm will receive a placebo infusion (saline) for 20 minutes prior to PCI.
Intervention MeSH terms: cyclo(Trp-Asp-Pro-Val-Leu)
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 23.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Coronary Atherosclerosis; Microvascular Dysfunction; Non-ST Elevation Myocardial Infarction

Summary:

      Percutaneous coronary intervention (PCI) for acute coronary syndromes frequently fails to
      restore myocardial perfusion despite establishing epicardial vessel patency. Endothelin-1
      (ET-1) is a potent vasoconstrictor and its expression is increased in atherosclerotic
      coronary arteries. Our hypothesis is that increased activity of the endogenous endothelin
      system contributes to microvascular dysfunction, and adjunctive therapy with an endothelin
      receptor antagonist will result in improved microvascular blood flow.

      Aims: The aims of the study are to assess in patients with non ST-elevation myocardial
      infarction, whether: 1) PCI causes an increase in coronary blood ET-1 level; 2) an endothelin
      receptor antagonist acutely improves coronary microvascular blood flow following PCI.

      Non-ST segment elevation myocardial infarction (NSTEMI) is one type of heart attack. It is
      defined as the development of heart muscle necrosis results from an acute interruption of
      blood supply to a part of the heart which is demonstrated by an elevation of cardiac markers
      Creatinine Kinase Isoenzyme Muscle/Brain Type (CK-MB) in the blood and the absence of
      ST-segment elevation in ECG (electrocardiography). ST-segment is a portion of ECG, its
      elevation indicates full thickness damage of heart muscle. Absence of ST-segment elevation in
      NSTEMI indicates partial thickness damage of heart muscle occurs. Therefore, NSTEMI is less
      severe type of heart attack compared to STEMI (ST-segment elevation myocardial infarction) in
      which full thickness damage of heart muscle occurs.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 18 years

          -  Clinical diagnosis of unstable angina or non ST-elevation myocardial infarction, and
             requiring clinically indicated PCI for the management of non ST elevation acute
             coronary syndrome.

        Exclusion Criteria:

          -  Systemic hypotension (systolic <90 mmHg)

          -  Heart failure or known ejection fraction < 30%

          -  Left main disease

          -  Culprit lesion is in a saphenous vein graft

          -  100% occlusion of the culprit vessel or culprit is an ostial right coronary stenosis

          -  Currently enrolled in other active cardiovascular investigational studies

          -  Severe endocrine, hepatic, or renal disorders

          -  Pregnancy or lactation

          -  Federal Medical Center inmates

          -  Inability or unwillingness to provide informed consent