Nitric Oxide-mediated Cardioprotection During Cardiac Surgery With Cardiopulmonary Bypass

Study Overview
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Brief Summary
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This prospective randomized study elucidates the effects of exogenous nitric oxide delivered to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass graft surgery with cardiopulmonary bypass.

Detailed Description
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The aim of this study is to investigate the effects of exogenous nitric oxide (NO) delivered to the extracorporeal circulation circuit for cardioprotection against ischemia-reperfusion injury during coronary artery bypass graft surgery (CABG) with cardiopulmonary bypass (CPB). A total of 60 patients with ischemic heart disease referred for CABG with CPB are included in prospective randomized study. Patients are randomized to receive standard treatment or surgery based on modified CPB protocol. According to modified protocol, 40-ppm NO is supplied to the CPB circuit during CABG. The primary endpoints are changes in cardiac troponin I (cTnI) levels at 6, 24, and 48 hours after surgery compared with baseline. The secondary end points are the changes in the levels of creatine kinase-muscle/brain (CK-MB) compared with baseline and vasoactive inotropic score (VIS) at 6, 24, and 48 hours. NO supplied to the CPB circuit exertes cardioprotective effect. Changes in cTnI, CK-MB, and VIS are considered indictors of the presence or absence of cardioprotective action of NO supplied to the CPB circuit.

Official Title
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Nitric Oxide-mediated Cardioprotection During Cardiac Surgery With Cardiopulmonary Bypass

Conditions
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Coronary Artery Disease, Coronary Artery Bypass, Cardiopulmonary Bypass, Nitric Oxide, Reperfusion Injury, Myocardial

Intervention / Treatment
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* Drug: Nitric Oxide
* Other: Standard CPB


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Coronary artery disease requiring coronary artery bypass grafting with the cardiopulmonary bypass. Exclusion Criteria: Non-elective surgery, age over 70 years, left ventricular ejection fraction less than 35%, history of myocardial infarction within three months prior to surgery, chronic atrial fibrillation, diabetes mellitus, and the elevated levels of cardiac specific markers within 12 h prior to the intervention.

Ages Eligible for Study
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Minimum Age: 56 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-center prospective, randomized, placebo-controlled study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nitric Oxide<br>Patients of this group receive treatment with exogenous gaseous nitric oxide supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease. | Drug: Nitric Oxide<br>* 40 ppm of exogenous gaseous nitric oxide is supplied directly to the oxygenator in the cardiopulmonary bypass circuit during coronary artery bypass grafting.<br>|
| Placebo Comparator: Standard CPB<br>Patients of this group receive sham-treatment without supplying nitric oxide to the cardiopulmonary bypass circuit during coronary artery bypass grafting for coronary artery disease. Considering dilution of nitric oxide at a high ratio of 1 to 25,000 in the gas mixture of the cardiopulmonary bypass circuit (CPB), no addition of any inert gas to the CPB circuit is required in sham-treatment group. | Other: Standard CPB<br>* Standard protocol of delivery of air gas mixture to the cardiopulmonary bypass circuit<br>* Other names: Cardiopulmonary bypass;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac troponin I change measure (cTnI) | Changes in the plasma level of cTnI (ng/mL) relative to the baseline value are measured at 6, 24, and 48 hours after surgery. | 48 hours (with intermediate measurements at 6 and 24 hours) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Creatine kinase-muscle/brain change measure (CK-MB) | Changes in the plasma level of CK-MB (U/L) relative to the baseline value are measured at 6, 24, and 48 hours after surgery. | 48 hours (with intermediate measurements at 6 and 24 hours) | 
| Vasoactive inotropic score measure (VIS) | Vasoactive inotropic score (VIS) is assessed at 6, 24, and 48 hours after surgery. VIS is calculated as follows: (dobutamine μg/kg/min × 1 + dopamine μg/kg/min × 1 + milrinone μg/kg/min × 10) + 100 × (adrenalin μg/kg/min + noradrenaline μg/kg/min + vasopressin μg/kg/min). | 48 hours (with intermediate measurements at 6 and 24 hours) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardioprotection, Ischemia-reperfusion injury, Nitric oxide, Cardiopulmonary bypass, Coronary artery bypass grafting