Coronary Artery Bypass Surgery
Conditions
Keywords
sodium nitrite, coronary artery bypass surgery, cardioprotection, myocardial injury
Brief summary
The purpose of this study is to determine whether sodium nitrite administration 24 hours prior to or during coronary artery bypass surgery protects the heart better from lack of blood flow which occurs as part of this type of operation. The study will also determine what the mechanisms of this cardioprotection are.
Detailed description
In recent years, there has been much interest in sodium nitrite as a cytoprotective agent in in vitro and animal models. A recent study undertaken in a canine model of myocardial infarction demonstrated a 50% reduction in myocardial injury following the administration of sodium nitrite prior to the ischemic event. In humans, the setting of coronary artery bypass surgery lends itself well to study potential cytoprotective agents. During cardiac surgery, the heart undergoes a period of ischemia allowing the surgeons to operate on the heart. This is followed by a period of reperfusion which in itself can add to cellular injury. Such injury can hinder post-operative myocardial recovery. The aim of this pilot study is to determine whether the cardioprotective effects of sodium nitrite demonstrated in animal models are translated in humans and to determine the exact underlying mechanisms of this cytoprotection. Patients undergoing coronary artery bypass grafting surgery who give written, informed consent will receive sodium nitrite 24 hours prior to surgery, during cardiac surgery or placebo. Myocardial injury will be assessed through the measurement of biochemical markers such as troponin T. Cardiac biopsy samples will be obtained to determine underlying molecular mechanisms of this cardioprotection. The other aim of this pilot study is to determine what dose of sodium nitrite (i.e. 0.2mcg/kg/min or 1mcg/kg/min) is optimal for cardioprotection. This study will form pilot data also for a larger clinical trial with clinical endpoints.
Interventions
DRUGsodium nitrite
0.2mcg/kg/min or 1mcg/kg/min intravenous for 30minutes at 1ml/min
DRUG0.9% sodium chloride
intravenous 0.9% sodium chloride over 30minutes at 1ml/min
Sponsors
University Hospital Birmingham NHS Foundation Trust
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients undergoing elective first time multi-vessel coronary artery bypass surgery * Older than 18 years of age
Exclusion criteria
* Significant psychiatric /neurological impairment that might prevent adherence to the requirements of the protocol or the ability to give informed consent * Inability to read the Information Sheet. * Redo operation * Age \>80 years * Pregnancy * Renal Impairment requiring pre-operative renal support * Diabetes Mellitus * Intended heart valve or additional surgery * Episodes of angina or ischemia within 48hours prior to the procedure
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Troponin T | 72 hours post release of aortic cross clamp | Biochemical marker of myocardial injury |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| troponin T | 12 hours post release of aortic cross clamp | — |
| Creatinine Kinase myocardial Fraction (CKMB) | 6 hours post release of aortic cross clamp | — |
| venous methemoglobinaemia | immediately before infusion of study drug | study drug means both sodium nitrite and placebo |
| plasma 8-isoprostane | before aortic cross clamp administration | — |
| Troponin T | 6 hours post release of aortic cross clamp | — |
| Cardiac output studies | upto 12 hours after release of aortic cross clamp | — |
| inotrope usage | up to 12 hours after release of aortic cross clamp | — |
| venous methemoglobinemia | immediately after infusion of study drug. | Study drug could be sodium nitrite or placebo and each infusion last 30minutes. |
| Plasma 8 isoprostane levels | 5minutes after discontinuation of cardiopulmonary bypass | — |
| Nitric oxide metabolites in cardiac tissue | before aortic cross clamp application | — |
Countries
United Kingdom
Contacts
Primary ContactSayqa Arif, MBChB
Backup ContactRobert Bonser, MD
Outcome results
None listed